Nitric Oxide (NO) Scaffolds the Peroxisomal Protein–Protein Interaction Network in Higher Plants

Total Page:16

File Type:pdf, Size:1020Kb

Nitric Oxide (NO) Scaffolds the Peroxisomal Protein–Protein Interaction Network in Higher Plants International Journal of Molecular Sciences Review Nitric Oxide (NO) Scaffolds the Peroxisomal Protein–Protein Interaction Network in Higher Plants Francisco J. Corpas * , Salvador González-Gordo and José M. Palma Antioxidant, Free Radical and Nitric Oxide in Biotechnology, Food and Agriculture Group, Department of Biochemistry, Cell and Molecular Biology of Plants, Estación Experimental del Zaidín, Spanish National Research Council (CSIC), C/ Profesor Albareda, 1, E-18008 Granada, Spain; [email protected] (S.G.-G.); [email protected] (J.M.P.) * Correspondence: [email protected] Abstract: The peroxisome is a single-membrane subcellular compartment present in almost all eukaryotic cells from simple protists and fungi to complex organisms such as higher plants and animals. Historically, the name of the peroxisome came from a subcellular structure that contained high levels of hydrogen peroxide (H2O2) and the antioxidant enzyme catalase, which indicated that this organelle had basically an oxidative metabolism. During the last 20 years, it has been shown that plant peroxisomes also contain nitric oxide (NO), a radical molecule than leads to a family of derived molecules designated as reactive nitrogen species (RNS). These reactive species can mediate post-translational modifications (PTMs) of proteins, such as S-nitrosation and tyrosine nitration, thus affecting their function. This review aims to provide a comprehensive overview of how NO could affect peroxisomal metabolism and its internal protein-protein interactions (PPIs). Remarkably, many of the identified NO-target proteins in plant peroxisomes are involved in the metabolism of reactive oxygen species (ROS), either in its generation or its scavenging. Therefore, Citation: Corpas, F.J.; González- it is proposed that NO is a molecule with signaling properties with the capacity to modulate the Gordo, S.; Palma, J.M. Nitric Oxide peroxisomal protein-protein network and consequently the peroxisomal functions, especially under (NO) Scaffolds the Peroxisomal adverse environmental conditions. Protein–Protein Interaction Network in Higher Plants. Int. J. Mol. Sci. 2021, Keywords: antioxidant; catalase; nitric oxide; peroxisome; reactive nitrogen species; S-nitrosation; 22, 2444. https://doi.org/10.3390/ tyrosine nitration ijms22052444 Academic Editor: Sławomir Borek 1. Overview of the Diversity of Peroxisomes in Eukaryotic Cells Received: 3 February 2021 Accepted: 25 February 2021 Peroxisomes are single-membrane subcellular organelles that appear in almost all Published: 28 February 2021 eukaryotic cells of the four kingdoms including protists, fungi, plants and animals [1–6]. The first structural identification of these organelles was done by electron microscope Publisher’s Note: MDPI stays neutral analyses in mouse kidney cells [7]. Years later, those new structures were isolated and with regard to jurisdictional claims in biochemically characterized in rat liver being recognized as a new cellular compartment published maps and institutional affil- having a prominent hydrogen peroxide (H2O2) metabolism [8,9]. From that time, studies iations. on peroxisomes were gradually extended to other organisms [1,10–18]. Figure1 shows some representative species, belonging to each kingdom, where peroxisomes have been studied, and Table1 displays various examples of the diversity of functions exerted by peroxisomes depending on the organism. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). Int. J. Mol. Sci. 2021, 22, 2444. https://doi.org/10.3390/ijms22052444 https://www.mdpi.com/journal/ijms Int. J. Mol. Sci. 2021, 22, 2444 2 of 14 Int. J. Mol. Sci. 2021, 22, 2444 2 of 14 Figure 1. Peroxisomes are single-membrane subcellular organelles that appear in almost all eukary- otic cells from the four kingdoms: protists, fungi, plants and animals. Figure 1. Peroxisomes are single-membrane subcellular organelles that appear in almost all eu- karyoticTable 1. Diversitycells from ofthe functions four kingdoms: exerted protists, by peroxisomes fungi, plants depending and animals. on the organism. Organism/Organ (Species) Peroxisomal Function Ref. Free-living marine diplonemidTable 1. DiversityPeroxisome of functions undergoes exerted by remodeling peroxisomes metabolism depending involving on the organism. the housing [19] (Diplonema papillatum) gluconeogenesis Organism/Organ (Species) Peroxisomal Function Ref. Ascomycete (Sclerotinia sclerotiorum) Peroxisome is involved in the fungi sexual development [20] Free-living marine diplone- Peroxisome undergoes remodeling metabolism involving the [19] Fungusmid (Diplonema (Alternaria papillatum alternate)) housing Peroxisome gluconeogenesis of the fungus is necessary for its pathogenesis in citrus [21] Ascomycete (Sclerotinia sclero- Peroxisomal malate dehydrogenase 2 connects lipid catabolism to Chlamydomonas Peroxisome is involved in the fungi sexual development [20] [22,23] tiorum) photosynthesis FungusPea leaves (Alternaria (Pisum sativum alternate)) Peroxisome Peroxisomes of the involvefungus is in nece leaf senescencessary for its pathogenesis in cit- [21] [24,25] ChlamydomonasLeaf tomato (Solanum lycopersicum)Peroxisomal Peroxisomes malate involve dehydrogenase in pathogen 2 connects defence lipid catabolism to [22,23] [26,27] photosynthesis Peroxisomal NADP-isocitrate dehydrogenase is required for stomatal PeaLeaves leaves (Arabidopsis (Pisum thalianasativum)) PeroxisomesmovementPeroxisomal involve in leaf senescence trehalose-6-phosphate phosphatase I is essential[24,25] for [28,29] flowering and development Leaf tomato (Solanum lycoper- Peroxisomes involve in pathogen defence [26,27] sicum) Peroxisomal and chloroplastic chorismate synthase, involved in shikimate Petunia (Petunia hybrida) [30] Leaves (Arabidopsis thaliana) Peroxisomalpathway, NADP-isocitrate are need for flower dehy developmentdrogenase is required for sto- [28,29] Mussels (Mytilus edulis)matal Peroxisomemovement proliferation in response to environmental pollutants [31] Peroxisomal trehalose-6-phosphate phosphatase I is essential for Impaired of peroxisomal fat oxidation induces hepatic lipid accumulation and Nile tilapia (Oreochromis niloticus) flowering and development [32] oxidative damage Petunia (Petunia hybrida) Peroxisomal and chloroplastic chorismate synthase, involved in [30] Rat liver (Rattus norvegicus)shikimate Peroxisomes pathway, participate are need for in theflower metabolism development of xenobiotic acyl compounds [33] Mussels (Mytilus edulis) PeroxisomeDefects proliferation in genes encoding in respon peroxisomalse to environmental proteins lead pollutants to a variety [31] of human Human (Homo sapiens) diseases. For example, X-linked adrenoleukodystrophy, acatalasemia, [34–38] Nile tilapia Impairedcerebro-hepato-renal of peroxisomal fat syndrome, oxidation etc.Host induces defense hepatic lipid ac- [32] (Oreochromis niloticus) cumulation and oxidative damage Rat liver PeroxisomesAt the morphological participate level,in the such metabolism as it has of been xenobiotic mentioned, acyl peroxisomes[33] seem to have (Rattus norvegicus) a verycompounds basic structure because they have a single lipid bilayer membrane that engulfs an amorphous matrix which sometimes has protein crystals. Figure2 shows the visualization Int. J. Mol. Sci. 2021, 22, 2444 3 of 14 Human Defects in genes encoding peroxisomal proteins lead to a variety [34–38] of human diseases. For example, X-linked adrenoleukodystrophy, (Homo sapiens) acatalasemia, cerebro-hepato-renal syndrome, etc. Host defense At the morphological level, such as it has been mentioned, peroxisomes seem to Int. J. Mol. Sci. 2021, 22, 2444 have a very basic structure because they have a single lipid bilayer membrane that3 en- of 14 gulfs an amorphous matrix which sometimes has protein crystals. Figure 2 shows the visualization of leaf peroxisomes from different plant species including transgenic Ara- bidopsis thaliana expressing cyan fluorescent protein (CFP) through the addition of pe- of leaf peroxisomes from different plant species including transgenic Arabidopsis thaliana roxisomal targeting signal 1 (PTS1), thus using a confocal scanning laser microscope expressing cyan fluorescent protein (CFP) through the addition of peroxisomal targeting (CLSM) peroxisomes appear as fluorescence punctuates (Figure 2a); in Cakile maritima signal 1 (PTS1), thus using a confocal scanning laser microscope (CLSM) peroxisomes using a transmission electron microscope (TEM) where the peroxisome is close to chlo- appear as fluorescence punctuates (Figure2a); in Cakile maritima using a transmission roplast and mitochondrion (Figure 2b); and in pea (Pisum sativum L.) leaf peroxisome electron microscope (TEM) where the peroxisome is close to chloroplast and mitochondrion housing the NADP-isocitrate dehydrogenase (NADP-ICDH) detected by its immuno- (Figure2b); and in pea ( Pisum sativum L.) leaf peroxisome housing the NADP-isocitrate localization by TEM (Figure 2c). Nevertheless, research on peroxisome morphology and dehydrogenase (NADP-ICDH) detected by its immunolocalization by TEM (Figure2c). biogenesisNevertheless, is a very research active on research peroxisome area morphology [39–42]. Thus, and a biogenesisrecent report, is a using very active Arabidopsis research seedlings,area [39– 42suggests]. Thus, the
Recommended publications
  • Integrative Genomic and Epigenomic Analyses Identified IRAK1 As a Novel Target for Chronic Inflammation-Driven Prostate Tumorigenesis
    bioRxiv preprint doi: https://doi.org/10.1101/2021.06.16.447920; this version posted June 16, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Integrative genomic and epigenomic analyses identified IRAK1 as a novel target for chronic inflammation-driven prostate tumorigenesis Saheed Oluwasina Oseni1,*, Olayinka Adebayo2, Adeyinka Adebayo3, Alexander Kwakye4, Mirjana Pavlovic5, Waseem Asghar5, James Hartmann1, Gregg B. Fields6, and James Kumi-Diaka1 Affiliations 1 Department of Biological Sciences, Florida Atlantic University, Florida, USA 2 Morehouse School of Medicine, Atlanta, Georgia, USA 3 Georgia Institute of Technology, Atlanta, Georgia, USA 4 College of Medicine, Florida Atlantic University, Florida, USA 5 Department of Computer and Electrical Engineering, Florida Atlantic University, Florida, USA 6 Department of Chemistry & Biochemistry and I-HEALTH, Florida Atlantic University, Florida, USA Corresponding Author: [email protected] (S.O.O) Running Title: Chronic inflammation signaling in prostate tumorigenesis bioRxiv preprint doi: https://doi.org/10.1101/2021.06.16.447920; this version posted June 16, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Abstract The impacts of many inflammatory genes in prostate tumorigenesis remain understudied despite the increasing evidence that associates chronic inflammation with prostate cancer (PCa) initiation, progression, and therapy resistance.
    [Show full text]
  • TRIM67 Inhibits Tumor Proliferation and Metastasis by Mediating
    Journal of Cancer 2020, Vol. 11 6025 Ivyspring International Publisher Journal of Cancer 2020; 11(20): 6025-6037. doi: 10.7150/jca.47538 Research Paper TRIM67 inhibits tumor proliferation and metastasis by mediating MAPK11 in Colorectal Cancer Ying Liu1*, Guiqi Wang1*, Xia Jiang1*, Wei Li1, Congjie Zhai1, Fangjian Shang1, Shihao Chen1, Zengren Zhao1 and Weifang Yu2 1. Department of General Surgery, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, The First Hospital of Hebei Medical University, Donggang Road No.89, Shijiazhuang, Hebei 050031, P.R. China. 2. Department of Endoscopy Center, The First Hospital of Hebei Medical University, Donggang Road No.89, Shijiazhuang, Hebei 050031, P.R. China. *These authors contributed equally to this work. Corresponding authors: Prof. Zengren Zhao or Weifang Yu, The First Hospital of Hebei Medical University, Donggang Road No.89, Shijiazhuang, Hebei 050031, P.R. China; Tel: +86 0311 85917217; E-mail: [email protected] or [email protected]. © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. Received: 2020.04.28; Accepted: 2020.08.04; Published: 2020.08.18 Abstract Purpose: We recently reported that tripartite motif-containing 67 (TRIM67) activates p53 to suppress colorectal cancer (CRC). However, the function and mechanism of TRIM67 in the inhibition of CRC cell proliferation and metastasis remains to be further elucidated. Methods: We detected the expression of TRIM67 in CRC tissues compared with normal tissues and confirmed its relationship with clinicopathological features.
    [Show full text]
  • Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
    Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase
    [Show full text]
  • Visnagin—A New Protectant Against Doxorubicin Cardiotoxicity? Inhibition of Mitochondrial Malate Dehydrogenase 2 (MDH2) and Beyond
    Editorial Page 1 of 5 Visnagin—a new protectant against doxorubicin cardiotoxicity? Inhibition of mitochondrial malate dehydrogenase 2 (MDH2) and beyond Lei Xi Pauley Heart Center, Division of Cardiology, Virginia Commonwealth University, Richmond, VA 23298-0204, USA Correspondence to: Lei Xi, MD, FAHA. Associate Professor, Division of Cardiology, Box 980204, Virginia Commonwealth University, 1101 East Marshall Street, Room 7-020C, Richmond, VA 23298-0204, USA. Email: [email protected]. Submitted Oct 08, 2015. Accepted for publication Oct 13, 2015. doi: 10.3978/j.issn.2305-5839.2015.10.43 View this article at: http://dx.doi.org/10.3978/j.issn.2305-5839.2015.10.43 Doxorubicin (DOX) is a broad-spectrum and potent with excessive ROS generation in mitochondria (12,13). anthracycline antibiotic that has been widely used since Due to the complex multi-factorial cellular and 1960s as a chemotherapeutic agent to treat a variety of molecular drivers underlying DOX cardiotoxicity, the human cancers (1). Despite its superior anti-cancer efficacy, optimal therapeutic approaches for protection against the clinical use of DOX is often limited by dose-dependent DOX cardiotoxicity have not yet been identified, despite cardiotoxicity, which may lead to irreversible dilated over 40 years of extensive research. Notably Herman et al. cardiomyopathy and congestive heart failure (2,3). Currently in 1972 first introduced bisdioxopiperazine compound as predominant theories for explaining DOX cardiotoxicity a cardioprotective agent against DOX cardiotoxicity (14). include the DOX-induced increase of oxidative stress in The subsequent research in this area led to identification cardiomyocytes (4), alteration of mitochondrial energetics of dexrazoxane, the only drug currently approved by the (5,6), and direct effect on DNA.
    [Show full text]
  • Identification of Differentially Expressed Genes in Human Bladder Cancer Through Genome-Wide Gene Expression Profiling
    521-531 24/7/06 18:28 Page 521 ONCOLOGY REPORTS 16: 521-531, 2006 521 Identification of differentially expressed genes in human bladder cancer through genome-wide gene expression profiling KAZUMORI KAWAKAMI1,3, HIDEKI ENOKIDA1, TOKUSHI TACHIWADA1, TAKENARI GOTANDA1, KENGO TSUNEYOSHI1, HIROYUKI KUBO1, KENRYU NISHIYAMA1, MASAKI TAKIGUCHI2, MASAYUKI NAKAGAWA1 and NAOHIKO SEKI3 1Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520; Departments of 2Biochemistry and Genetics, and 3Functional Genomics, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan Received February 15, 2006; Accepted April 27, 2006 Abstract. Large-scale gene expression profiling is an effective CKS2 gene not only as a potential biomarker for diagnosing, strategy for understanding the progression of bladder cancer but also for staging human BC. This is the first report (BC). The aim of this study was to identify genes that are demonstrating that CKS2 expression is strongly correlated expressed differently in the course of BC progression and to with the progression of human BC. establish new biomarkers for BC. Specimens from 21 patients with pathologically confirmed superficial (n=10) or Introduction invasive (n=11) BC and 4 normal bladder samples were studied; samples from 14 of the 21 BC samples were subjected Bladder cancer (BC) is among the 5 most common to microarray analysis. The validity of the microarray results malignancies worldwide, and the 2nd most common tumor of was verified by real-time RT-PCR. Of the 136 up-regulated the genitourinary tract and the 2nd most common cause of genes we detected, 21 were present in all 14 BCs examined death in patients with cancer of the urinary tract (1-7).
    [Show full text]
  • Role of MDH2 Pathogenic Variant in Pheochromocytoma and Paraganglioma Patients
    ARTICLE © American College of Medical Genetics and Genomics Role of MDH2 pathogenic variant in pheochromocytoma and paraganglioma patients Bruna Calsina, MSc, Mercedes Robledo, PhD et al.# Purpose: MDH2 (malate dehydrogenase 2) has recently been variant (c.429+1G>T). All were germline and those with available proposed as a novel potential pheochromocytoma/paraganglioma biochemical data, corresponded to noradrenergic PPGL. (PPGL) susceptibility gene, but its role in the disease has not been MDH2 MDH2 Conclusion: This study suggests that pathogenic variants addressed. This study aimed to determine the prevalence of may play a role in PPGL susceptibility and that they might be pathogenic variants among PPGL patients and determine the responsible for less than 1% of PPGLs in patients without associated phenotype. pathogenic variants in other major PPGL driver genes, a prevalence Methods: Eight hundred thirty patients with PPGLs, negative for similar to the one recently described for other PPGL genes. the main PPGL driver genes, were included in the study. However, more epidemiological data are needed to recommend Interpretation of variants of unknown significance (VUS) was MDH2 testing in patients negative for other major PPGL genes. performed using an algorithm based on 20 computational predictions, by implementing cell-based enzymatic and immuno- Genetics in Medicine (2018) 20:1652–1662; https://doi.org/10.1038/ fluorescence assays, and/or by using a molecular dynamics s41436-018-0068-7 simulation approach. Results: Five variants with potential
    [Show full text]
  • Gene Number in Species of Astereae That Have Different Chromosome Numbers (Plant Evolution/Isozymes/Aneuploidy/Compositae) L
    Proc. Nati. Acad. Sci. USA Vol. 78, No. 6, pp. 3726-3729, June 1981 Evolution Gene number in species of Astereae that have different chromosome numbers (plant evolution/isozymes/aneuploidy/Compositae) L. D. GOTTLIEB Department of Genetics, University of California, Davis, California 95616 Communicated by P. H. Raven, February 18, 1981 ABSTRACT Differencesin the gameticchromosome numbers MATERIALS AND METHODS (n = 4, 5, 9) ofspecies.in the Astereae tribe ofthe Compositae have Seven species were examined: Machaeranthera tenuis, n = 4 been variously .interpreted. One hypothesis proposes that n = 9 (Jackson 7607, Ft. Davis, TX); M. mexicana, n = 4 (Jackson was the original base number ofthe group and that the lower num- bers resulted from aneuploid reduction. The alternative hypoth- 7547, 57 miles west of Durango, Mexico); M. boltoniae, n = 4 esis asserts that the ancestral base number was n = 4 or n = 5 and (Jackson 7551, 27 miles north of Durango, Mexico); M. turneri that species in which n = 9 are allotetraploids derived by hybrid- n = 5 (Jackson 7564, Meoqui, Chihauhua, Mexico); M. brevi- ization between taxa with the lower numbers. Electrophoretic lingulata, n = 9 (Jackson 7526, Aguascalientes, Mexico); Aster analysis of 17 enzyme systems' in.five species of Machaeranthera, riparius, n = 5 Jackson 'Lordsburg, NM, and Jackson 7550, 27 in which n = 4, 5, and 9, and two species of Aster in which n = miles north of Durango, Mexico); Aster hydrophilus, n = 9 5 and 9,-demonstrates that all of these species have the same num- (Jackson 7640, Beatty NV). The seeds were generously provided ber of gene loci specifying the tested enzymes.
    [Show full text]
  • Rescue of TCA Cycle Dysfunction for Cancer Therapy
    Journal of Clinical Medicine Review Rescue of TCA Cycle Dysfunction for Cancer Therapy 1, 2, 1 2,3 Jubert Marquez y, Jessa Flores y, Amy Hyein Kim , Bayalagmaa Nyamaa , Anh Thi Tuyet Nguyen 2, Nammi Park 4 and Jin Han 1,2,4,* 1 Department of Health Science and Technology, College of Medicine, Inje University, Busan 47392, Korea; [email protected] (J.M.); [email protected] (A.H.K.) 2 Department of Physiology, College of Medicine, Inje University, Busan 47392, Korea; jefl[email protected] (J.F.); [email protected] (B.N.); [email protected] (A.T.T.N.) 3 Department of Hematology, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia 4 Cardiovascular and Metabolic Disease Center, Paik Hospital, Inje University, Busan 47392, Korea; [email protected] * Correspondence: [email protected]; Tel.: +8251-890-8748 Authors contributed equally. y Received: 10 November 2019; Accepted: 4 December 2019; Published: 6 December 2019 Abstract: Mitochondrion, a maternally hereditary, subcellular organelle, is the site of the tricarboxylic acid (TCA) cycle, electron transport chain (ETC), and oxidative phosphorylation (OXPHOS)—the basic processes of ATP production. Mitochondrial function plays a pivotal role in the development and pathology of different cancers. Disruption in its activity, like mutations in its TCA cycle enzymes, leads to physiological imbalances and metabolic shifts of the cell, which contributes to the progression of cancer. In this review, we explored the different significant mutations in the mitochondrial enzymes participating in the TCA cycle and the diseases, especially cancer types, that these malfunctions are closely associated with. In addition, this paper also discussed the different therapeutic approaches which are currently being developed to address these diseases caused by mitochondrial enzyme malfunction.
    [Show full text]
  • Differentially Expressed Proteins in the Skin Mucus of Atlantic
    Rajan et al. BMC Veterinary Research 2013, 9:103 http://www.biomedcentral.com/1746-6148/9/103 RESEARCH ARTICLE Open Access Differentially expressed proteins in the skin mucus of Atlantic cod (Gadus morhua) upon natural infection with Vibrio anguillarum Binoy Rajan, Jep Lokesh, Viswanath Kiron and Monica F Brinchmann* Abstract Background: Vibriosis caused by V. anguillarum is a commonly encountered disease in Atlantic cod farms and several studies indicate that the initiation of infection occurs after the attachment of the pathogen to the mucosal surfaces (gut, skin and gills) of fish. Therefore it is necessary to investigate the role of different mucosal components in fish upon V. anguillarum infection. The present study has two parts; in the first part we analyzed the differential expression of skin mucus proteins from Atlantic cod naturally infected with V. anguillarum using two dimensional gel electrophoresis coupled with mass spectrometry. In the second part, a separate bath challenge experiment with V. anguillarum was conducted to assess the mRNA levels of the genes in skin tissue, corresponding to the selected proteins identified in the first part. Results: Comparative proteome analysis of skin mucus of cod upon natural infection with V. anguillarum revealed key immune relevant proteins like calpain small subunit 1, glutathione-S-transferase omega 1, proteasome 26S subunit, 14-kDa apolipoprotein, beta 2-tubulin, cold inducible RNA binding protein, malate dehydrogenase 2 (mitochondrial) and type II keratin that exhibited significant differential expression. Additionally a number of protein spots which showed large variability amongst individual fish were also identified. Some of the proteins identified were mapped to the immunologically relevant JNK (c-Jun N-terminal kinases) signalling pathway that is connected to cellular events associated with pathogenesis.
    [Show full text]
  • Naegleria Fowleri: Protein Structures to Facilitate Drug Discovery for The
    bioRxiv preprint doi: https://doi.org/10.1101/2020.10.20.327296; this version posted October 22, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 1 Naegleria fowleri: protein structures to facilitate drug discovery for the 2 deadly, pathogenic free-living amoeba 3 Kayleigh Barrett1,8, Logan Tillery1,8, Jenna Goldstein†9, Jared W. Lassner†9, Bram Osterhout†9, Nathan L. †9 †9 †9 1,8 1,8 3,8 3,8 4 Tran , Lily Xu , Ryan M. Young , Justin Craig , Ian Chun , David M. Dranow , Jan Abendroth , 5 Silvia L. Delker3,8, Douglas R. Davies3,8, Stephen J. Mayclin3,8, Brandy Calhoun3,8, Madison J. 6 Bolejack3,8, Bart Staker2,8, Sandhya Subramanian2,8, Isabelle Phan2,8, Donald D. Lorimer3,8, Peter J. Δ 7 Myler2,8,10,11,12, Thomas E. Edwards3,8, Dennis E. Kyle4, Christopher A. Rice4 , James C. Morris5, James 8 W. Leahy6, Roman Manetsch7, Lynn K. Barrett1,8, Craig L. Smith9, Wesley C. Van Voorhis1,8,12 9 10 1Department of Medicine, Division Allergy and Infectious Disease, Center for Emerging and Re- 11 emerging Infectious Disease (CERID) University of Washington, Seattle, WA, USA 12 2Seattle Children’s Research Institute, Seattle, WA, USA 13 3UCB Pharma, Bainbridge Island, WA, USA 14 4Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, USA 15 5Eukaryotic Pathogens Innovation Center, Department of Genetics and Biochemistry, Clemson 16 University, Clemson, SC, USA 17 6Department of Chemistry, University of South Florida, Tampa, FL, USA 18 7Department of Chemistry and Chemical Biology and Department of Pharmaceutical Sciences, 19 Northeastern University, Boston, MA, USA 20 8Seattle Structural Genomics Center for Infectious Diseases, Seattle, WA, USA 21 9Department of Biology, Washington University, St.
    [Show full text]
  • A Novel Malate Dehydrogenase 2 Inhibitor Suppresses Hypoxia-Induciblefactor-1 by Regulating Mitochondrial Respiration
    RESEARCH ARTICLE A Novel Malate Dehydrogenase 2 Inhibitor Suppresses Hypoxia-InducibleFactor-1 by Regulating Mitochondrial Respiration Hyun Seung Ban1,2☯, Xuezhen Xu3☯, Kusik Jang3, Inhyub Kim4,5, Bo-Kyung Kim4, Kyeong Lee3*, Misun Won4,5* 1 Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea, 2 Biomolecular Science, University of Science and Technology, Daejeon, Korea, 3 College of Pharmacy, Dongguk University-Seoul, Goyang, Korea, 4 Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea, 5 Functional Genomics, a11111 University of Science and Technology, Daejeon, Korea ☯ These authors contributed equally to this work. * [email protected] (MW); [email protected] (KL) Abstract OPEN ACCESS We previously reported that hypoxia-inducible factor (HIF)-1 inhibitor LW6, an aryloxyacety- Citation: Ban HS, Xu X, Jang K, Kim I, Kim B-K, Lee K, et al. (2016) A Novel Malate Dehydrogenase2 lamino benzoic acid derivative, inhibits malate dehydrogenase 2 (MDH2) activity during the Inhibitor Suppresses Hypoxia-Inducible Factor-1 by mitochondrial tricarboxylic acid (TCA) cycle. In this study, we present a novel MDH2 inhibi- Regulating Mitochondrial Respiration. PLoS ONE 11 tor compound 7 containing benzohydrazide moiety, which was identified through structure- (9): e0162568. doi:10.1371/journal.pone.0162568 based virtual screening of chemical library. Similar to LW6, compound 7 inhibited MDH2 Editor: Jung Weon Lee, Seoul National University activity in a competitive fashion, thereby reducing NADH level. Consequently, compound 7 College of Pharmacy, REPUBLIC OF KOREA reduced oxygen consumption and ATP production during the mitochondrial respiration Received: June 10, 2016 cycle, resulting in increased intracellular oxygen concentration.
    [Show full text]
  • Proteomic Identification of Target Proteins of Thiodigalactoside in White Adipose Tissue from Diet-Induced Obese Rats
    Int. J. Mol. Sci. 2015, 16, 14441-14463; doi:10.3390/ijms160714441 OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 www.mdpi.com/journal/ijms Article Proteomic Identification of Target Proteins of Thiodigalactoside in White Adipose Tissue from Diet-Induced Obese Rats Hilal Ahmad Parray and Jong Won Yun * Department of Biotechnology, Daegu University, Kyungsan, Kyungbuk 712-714, Korea; E-Mail: [email protected] * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +82-53-850-6556; Fax: +82-53-850-6559. Academic Editor: David Sheehan Received: 16 May 2015 / Accepted: 18 June 2015 / Published: 25 June 2015 Abstract: Previously, galectin-1 (GAL1) was found to be up-regulated in obesity-prone subjects, suggesting that use of a GAL1 inhibitor could be a novel therapeutic approach for treatment of obesity. We evaluated thiodigalactoside (TDG) as a potent inhibitor of GAL1 and identified target proteins of TDG by performing comparative proteome analysis of white adipose tissue (WAT) from control and TDG-treated rats fed a high fat diet (HFD) using two dimensional gel electrophoresis (2-DE) combined with MALDI-TOF-MS. Thirty-two spots from a total of 356 matched spots showed differential expression between control and TDG-treated rats, as identified by peptide mass fingerprinting. These proteins were categorized into groups such as carbohydrate metabolism, tricarboxylic acid (TCA) cycle, signal transduction, cytoskeletal, and mitochondrial proteins based on functional analysis using Protein Annotation Through Evolutionary Relationship (PANTHER) and Database for Annotation, Visualization, Integrated Discovery (DAVID) classification. One of the most striking findings of this study was significant changes in Carbonic anhydrase 3 (CA3), Voltage-dependent anion channel 1 (VDAC1), phosphatidylethanolamine-binding protein 1 (PEBP1), annexin A2 (ANXA2) and lactate dehydrogenase A chain (LDHA) protein levels between WAT from control and TDG-treated groups.
    [Show full text]