Aldehyde Dehydrogenase 2 Activation and Coevolution of Its Εpkc
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Alternative Acetate Production Pathways in Chlamydomonas Reinhardtii During Dark Anoxia and the Dominant Role of Chloroplasts in Fermentative Acetate Productionw
This article is a Plant Cell Advance Online Publication. The date of its first appearance online is the official date of publication. The article has been edited and the authors have corrected proofs, but minor changes could be made before the final version is published. Posting this version online reduces the time to publication by several weeks. Alternative Acetate Production Pathways in Chlamydomonas reinhardtii during Dark Anoxia and the Dominant Role of Chloroplasts in Fermentative Acetate ProductionW Wenqiang Yang,a,1 Claudia Catalanotti,a Sarah D’Adamo,b Tyler M. Wittkopp,a,c Cheryl J. Ingram-Smith,d Luke Mackinder,a Tarryn E. Miller,b Adam L. Heuberger,e Graham Peers,f Kerry S. Smith,d Martin C. Jonikas,a Arthur R. Grossman,a and Matthew C. Posewitzb a Carnegie Institution for Science, Department of Plant Biology, Stanford, California 94305 b Colorado School of Mines, Department of Chemistry and Geochemistry, Golden, Colorado 80401 c Stanford University, Department of Biology, Stanford, California 94305 d Clemson University, Department of Genetics and Biochemistry, Clemson, South Carolina 29634 e Colorado State University, Proteomics and Metabolomics Facility, Fort Collins, Colorado 80523 f Colorado State University, Department of Biology, Fort Collins, Colorado 80523 ORCID ID: 0000-0001-5600-4076 (W.Y.) Chlamydomonas reinhardtii insertion mutants disrupted for genes encoding acetate kinases (EC 2.7.2.1) (ACK1 and ACK2) and a phosphate acetyltransferase (EC 2.3.1.8) (PAT2, but not PAT1) were isolated to characterize fermentative acetate production. ACK1 and PAT2 were localized to chloroplasts, while ACK2 and PAT1 were shown to be in mitochondria. -
The Aldehyde Dehydrogenase ALDH2*2 Allele Exhibits Dominance Over ALDH2*1 in Transduced Hela Cells
The aldehyde dehydrogenase ALDH2*2 allele exhibits dominance over ALDH2*1 in transduced HeLa cells. Q Xiao, … , T Johnston, D W Crabb J Clin Invest. 1995;96(5):2180-2186. https://doi.org/10.1172/JCI118272. Research Article Individuals heterozygous or homozygous for the variant aldehyde dehydrogenase (ALDH2) allele (ALDH2*2), which encodes a protein differing only at residue 487 from the normal protein, have decreased ALDH2 activity in liver extracts and experience cutaneous flushing when they drink alcohol. The mechanisms by which this allele exerts its dominant effect is unknown. To study this effect, the human ALDH2*1 cDNA was cloned and the ALDH2*2 allele was generated by site-directed mutagenesis. These cDNAs were transduced using retroviral vectors into HeLa and CV1 cells, which do not express ALDH2. The normal allele directed synthesis of immunoreactive ALDH2 protein (ALDH2E) with the expected isoelectric point. Extracts of these cells contained increased aldehyde dehydrogenase activity with low Km for the aldehyde substrate. The ALDH2*2 allele directed synthesis of mRNA and immunoreactive protein (ALDH2K), but the protein lacked enzymatic activity. When ALDH2*1-expressing cells were transduced with ALDH2*2 vectors, both mRNAs were expressed and immunoreactive proteins with isoelectric points ranging between those of ALDH2E and ALDH2K were present, indicating that the subunits formed heteromers. ALDH2 activity in these cells was reduced below that of the parental ALDH2*1-expressing cells. Thus, the ALDH2*2 allele is sufficient to cause ALDH2 deficiency in vitro. Find the latest version: https://jci.me/118272/pdf The Aldehyde Dehydrogenase ALDH2*2 Allele Exhibits Dominance over ALDH2*1 in Transduced HeLa Cells Qing Xiao, * Henry Weiner,* Timothy Johnston,* and David W. -
Combined Treatment of Isoflavone Supplementation and Exercise
Yoon et al. Journal of the International Society of Sports Nutrition 2014, 11:29 http://www.jissn.com/content/11/1/29 RESEARCH ARTICLE Open Access Combined treatment of isoflavone supplementation and exercise restores the changes in hepatic protein expression in ovariectomized rats - a proteomics approach Sun Yoon1, Joomin Lee2 and Seung-Min Lee1* Abstract Background: Postmenopausal women experience adverse physiological changes caused by estrogen deprivation. Here, we hypothesized that the administration of isoflavone, a phytoestrogn, and/or physical exercise could reverse changes in the levels of hepatic enzymes disturbed by loss of estrogen to ameliorate postmenopause-related health problems. Methods: Thirty-week-old female Sprague–Dawley rats were divided into five groups: a sham-operated (SHAM) group, ovariectomized groups on a regular diet with exercise (EXE) and without exercise (OVX), and ovariectomized groups on an isoflavone supplemented diet with (ISO + EXE) and without exercise (ISO). Proteomic tools were employed to identify candidate hepatic proteins that were differentially expressed among the five animal groups. Results: INMT was detected in the SHAM but not in all of the ovariectomized rats. Seven proteins (PPIA, AKR1C3, ALDH2, PSME2, BUCS1, OTC, and GAMT) were identified to have differential expression among the groups. When compared to the SHAM group, the ovariectomy elevated the levels of PPIA, BUCS1, PSME2, AKR1C3, and GAMT while decreasing ALDH2 and OTC. Among these OVX-induced changes, OVX-increased BUCS1 and GAMT levels were noticeably decreased by ISO or EXE and further greatly down-regulated by ISO + EXE. In the case of PSME2, ISO and EXE further increased OVX-upregulated expression levels but ISO + EXE greatly reduced OVX-increased levels. -
Altered Expression and Function of Mitochondrial Я-Oxidation Enzymes
0031-3998/01/5001-0083 PEDIATRIC RESEARCH Vol. 50, No. 1, 2001 Copyright © 2001 International Pediatric Research Foundation, Inc. Printed in U.S.A. Altered Expression and Function of Mitochondrial -Oxidation Enzymes in Juvenile Intrauterine-Growth-Retarded Rat Skeletal Muscle ROBERT H. LANE, DAVID E. KELLEY, VLADIMIR H. RITOV, ANNA E. TSIRKA, AND ELISA M. GRUETZMACHER Department of Pediatrics, UCLA School of Medicine, Mattel Children’s Hospital at UCLA, Los Angeles, California 90095, U.S.A. [R.H.L.]; and Departments of Internal Medicine [D.E.K., V.H.R.] and Pediatrics [R.H.L., A.E.T., E.M.G.], University of Pittsburgh School of Medicine, Magee-Womens Research Institute, Pittsburgh, Pennsylvania 15213, U.S.A. ABSTRACT Uteroplacental insufficiency and subsequent intrauterine creased in IUGR skeletal muscle mitochondria, and isocitrate growth retardation (IUGR) affects postnatal metabolism. In ju- dehydrogenase activity was unchanged. Interestingly, skeletal venile rats, IUGR alters skeletal muscle mitochondrial gene muscle triglycerides were significantly increased in IUGR skel- expression and reduces mitochondrial NADϩ/NADH ratios, both etal muscle. We conclude that uteroplacental insufficiency alters of which affect -oxidation flux. We therefore hypothesized that IUGR skeletal muscle mitochondrial lipid metabolism, and we gene expression and function of mitochondrial -oxidation en- speculate that the changes observed in this study play a role in zymes would be altered in juvenile IUGR skeletal muscle. To test the long-term morbidity associated with IUGR. (Pediatr Res 50: this hypothesis, mRNA levels of five key mitochondrial enzymes 83–90, 2001) (carnitine palmitoyltransferase I, trifunctional protein of -oxi- dation, uncoupling protein-3, isocitrate dehydrogenase, and mi- Abbreviations tochondrial malate dehydrogenase) and intramuscular triglycer- CPTI, carnitine palmitoyltransferase I ides were quantified in 21-d-old (preweaning) IUGR and control IUGR, intrauterine growth retardation rat skeletal muscle. -
Nutritional Vitamin B6 Deficiency Impairs Lipid Me Tabolism and Leads
J Nutr Sci Vitaminol, 47, 306-310, 2001 Xanthurenic Acid Inhibits Metal Ion-Induced Lipid Peroxidation and Protects NADP-Isocitrate Dehydrogenase from Oxidative Inactivation Keiko MURAKAMI,Masae ITO and Masataka YOSHINO* Department of Biochemistry, Aichi Medical University School of Medicine,Nagakute, Aichi 480-1195, Japan (ReceivedJanuary 26, 2001) Summary Vitamin B6 deficiency increases the lipid peroxidation and the synthesis of xanthurenic acid from tryptophan. Antioxidant properties of xanthurenic acid were exam ined in relation to the coordination of transition metals. Xanthurenic acid inhibited the for mation of thiobarbituric acid-reactive substances as a marker of iron-mediated lipid peroxi dation and copper-dependent oxidation of low density lipoprotein. NADP-isocitrate dehydro genase (EC 1.1.1.42), a principal NADPH-generating enzyme for the antioxidant defense system, was inactivated by reduced iron and copper, and xanthurenic acid protected the en zyme from the Fe2+-mediated inactivation. Xanthurenic acid may participate in the en hanced regeneration of reduced glutathione by stimulating the NADPH supply. Xanthurenic acid further enhanced the autooxidation of Fe2+ ion. Other tryptophan metabolites such as kynurenic acid and various quinoline compounds did not inhibit the lipid peroxidation and the inactivation of NADP-isocitrate dehydrogenase, and they showed little or no effect on the Fe2+ autooxidation. The antioxidant properties of xanthurenic acid are related to the metal-chelating activity and probably to the enhanced oxidation of reduced transition met als as a prooxidant, and this action may be due to the electron deficient nature of this com pound. Key Words xanthurenic acid, antioxidant, LDL, NADP-isocitrate dehydrogenase, reactive oxygen species Nutritional vitamin B6 deficiency impairs lipid me Lipid peroxidation. -
Table 2. Significant
Table 2. Significant (Q < 0.05 and |d | > 0.5) transcripts from the meta-analysis Gene Chr Mb Gene Name Affy ProbeSet cDNA_IDs d HAP/LAP d HAP/LAP d d IS Average d Ztest P values Q-value Symbol ID (study #5) 1 2 STS B2m 2 122 beta-2 microglobulin 1452428_a_at AI848245 1.75334941 4 3.2 4 3.2316485 1.07398E-09 5.69E-08 Man2b1 8 84.4 mannosidase 2, alpha B1 1416340_a_at H4049B01 3.75722111 3.87309653 2.1 1.6 2.84852656 5.32443E-07 1.58E-05 1110032A03Rik 9 50.9 RIKEN cDNA 1110032A03 gene 1417211_a_at H4035E05 4 1.66015788 4 1.7 2.82772795 2.94266E-05 0.000527 NA 9 48.5 --- 1456111_at 3.43701477 1.85785922 4 2 2.8237185 9.97969E-08 3.48E-06 Scn4b 9 45.3 Sodium channel, type IV, beta 1434008_at AI844796 3.79536664 1.63774235 3.3 2.3 2.75319499 1.48057E-08 6.21E-07 polypeptide Gadd45gip1 8 84.1 RIKEN cDNA 2310040G17 gene 1417619_at 4 3.38875643 1.4 2 2.69163229 8.84279E-06 0.0001904 BC056474 15 12.1 Mus musculus cDNA clone 1424117_at H3030A06 3.95752801 2.42838452 1.9 2.2 2.62132809 1.3344E-08 5.66E-07 MGC:67360 IMAGE:6823629, complete cds NA 4 153 guanine nucleotide binding protein, 1454696_at -3.46081884 -4 -1.3 -1.6 -2.6026947 8.58458E-05 0.0012617 beta 1 Gnb1 4 153 guanine nucleotide binding protein, 1417432_a_at H3094D02 -3.13334396 -4 -1.6 -1.7 -2.5946297 1.04542E-05 0.0002202 beta 1 Gadd45gip1 8 84.1 RAD23a homolog (S. -
Isocitrate Dehydrogenase Activity Assay Kit (MAK062)
Isocitrate Dehydrogenase Activity Assay Kit Catalog Number MAK062 Storage Temperature –20 C TECHNICAL BULLETIN Product Description Developer 1 vl Isocitrate dehydrogenase (IDH) catalyzes the Catalog Number MAK062E conversion of isocitrate to -ketoglutarate. In eukaryotes, there are three isozymes of IDH, the IDH Positive Control (NADP+) 20 L mitochondrial IDH2 and IDH3, and the cytoplasmic/ Catalog Number MAK062F peroxisomal IDH1. All three IDH family members require the presence of a divalent cation (Mg2+ or Mn2+) NADH Standard, 0.5 mole 1 vl and either the electron-accepting cofactor NADP+ (IDH1 Catalog Number MAK062G and IDH2) or NAD+ (IDH3) for their enzymatic activity. IDH1 and IDH2 mutations resulting in neomorphic Reagents and Equipment Required but Not enzymatic activity are found in certain cancers such as Provided. glioblastoma, acute myeloid leukemia, and colon 96 well flat-bottom plate – It is recommended to use cancer. This neoactivity shows a change in the clear plates for colorimetric assays. substrate specificity resulting in the conversion of Spectrophotometric multiwell plate reader -ketoglutarate to 2-hydroxyglutarate. Mutations in IDH family members are also associated with Ollier disease Precautions and Disclaimer and Maffucci syndrome. This product is for R&D use only, not for drug, household, or other uses. Please consult the Material The Isocitrate Dehydrogenase Activity Assay kit Safety Data Sheet for information regarding hazards provides a simple and direct procedure for measuring and safe handling practices. + + + NADP -dependent, NAD -dependent, or both NADP + and NAD -dependent IDH activity in a variety of Preparation Instructions samples. IDH activity is determined using isocitrate as Briefly centrifuge vials before opening. -
Supplementary Materials
1 Supplementary Materials: Supplemental Figure 1. Gene expression profiles of kidneys in the Fcgr2b-/- and Fcgr2b-/-. Stinggt/gt mice. (A) A heat map of microarray data show the genes that significantly changed up to 2 fold compared between Fcgr2b-/- and Fcgr2b-/-. Stinggt/gt mice (N=4 mice per group; p<0.05). Data show in log2 (sample/wild-type). 2 Supplemental Figure 2. Sting signaling is essential for immuno-phenotypes of the Fcgr2b-/-lupus mice. (A-C) Flow cytometry analysis of splenocytes isolated from wild-type, Fcgr2b-/- and Fcgr2b-/-. Stinggt/gt mice at the age of 6-7 months (N= 13-14 per group). Data shown in the percentage of (A) CD4+ ICOS+ cells, (B) B220+ I-Ab+ cells and (C) CD138+ cells. Data show as mean ± SEM (*p < 0.05, **p<0.01 and ***p<0.001). 3 Supplemental Figure 3. Phenotypes of Sting activated dendritic cells. (A) Representative of western blot analysis from immunoprecipitation with Sting of Fcgr2b-/- mice (N= 4). The band was shown in STING protein of activated BMDC with DMXAA at 0, 3 and 6 hr. and phosphorylation of STING at Ser357. (B) Mass spectra of phosphorylation of STING at Ser357 of activated BMDC from Fcgr2b-/- mice after stimulated with DMXAA for 3 hour and followed by immunoprecipitation with STING. (C) Sting-activated BMDC were co-cultured with LYN inhibitor PP2 and analyzed by flow cytometry, which showed the mean fluorescence intensity (MFI) of IAb expressing DC (N = 3 mice per group). 4 Supplemental Table 1. Lists of up and down of regulated proteins Accession No. -
Isocitrate Dehydrogenase 1 (NADP+) (I5036)
Isocitrate Dehydrogenase 1 (NADP+), human recombinant, expressed in Escherichia coli Catalog Number I5036 Storage Temperature –20 °C CAS RN 9028-48-2 IDH1 and IDH2 have frequent genetic alterations in EC 1.1.1.42 acute myeloid leukemia4 and better understanding of Systematic name: Isocitrate:NADP+ oxidoreductase these mutations may lead to an improvement of (decarboxylating) individual cancer risk assessment.6 In addition other studies have shown loss of IDH1 in bladder cancer Synonyms: IDH1, cytosolic NADP(+)-dependent patients during tumor development suggesting this may isocitrate dehydrogenase, isocitrate:NADP+ be involved in tumor progression and metastasis.7 oxidoreductase (decarboxylating), Isocitric Dehydrogenase, ICD1, PICD, IDPC, ICDC, This product is lyophilized from a solution containing oxalosuccinate decarboxylase Tris-HCl, pH 8.0, with trehalose, ammonium sulfate, and DTT. Product Description Isocitrate dehydrogenase (NADP+) [EC 1.1.1.42] is a Purity: ³90% (SDS-PAGE) Krebs cycle enzyme, which converts isocitrate to a-ketoglutarate. The flow of isocitrate through the Specific activity: ³80 units/mg protein glyoxylate bypass is regulated by phosphorylation of isocitrate dehydrogenase, which competes for a Unit definition: 1 unit corresponds to the amount of 1 common substrate (isocitrate) with isocitrate lyase. enzyme, which converts 1 mmole of DL-isocitrate to The activity of the enzyme is dependent on the a-ketoglutarate per minute at pH 7.4 and 37 °C (NADP formation of a magnesium or manganese-isocitrate as cofactor). The activity is measured by observing the 2 complex. reduction of NADP to NADPH at 340 nm in the 7 presence of 4 mM DL-isocitrate and 2 mM MnSO4. -
Comparative Proteomics Analysis of Human Liver Microsomes and S9
DMD Fast Forward. Published on November 7, 2019 as DOI: 10.1124/dmd.119.089235 This article has not been copyedited and formatted. The final version may differ from this version. DMD # 89235 Comparative Proteomics Analysis of Human Liver Microsomes and S9 Fractions Xinwen Wang, Bing He, Jian Shi, Qian Li, and Hao-Jie Zhu Department of Clinical Pharmacy, University of Michigan, Ann Arbor, Michigan (X.W., B.H., J.S., H.-J.Z.); and School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu, 210009 (Q.L.) Downloaded from dmd.aspetjournals.org at ASPET Journals on October 2, 2021 1 DMD Fast Forward. Published on November 7, 2019 as DOI: 10.1124/dmd.119.089235 This article has not been copyedited and formatted. The final version may differ from this version. DMD # 89235 Running title: Comparative Proteomics of Human Liver Microsomes and S9 Corresponding author: Hao-Jie Zhu Ph.D. Department of Clinical Pharmacy University of Michigan College of Pharmacy 428 Church Street, Room 4565 Downloaded from Ann Arbor, MI 48109-1065 Tel: 734-763-8449, E-mail: [email protected] dmd.aspetjournals.org Number of words in Abstract: 250 at ASPET Journals on October 2, 2021 Number of words in Introduction: 776 Number of words in Discussion: 2304 2 DMD Fast Forward. Published on November 7, 2019 as DOI: 10.1124/dmd.119.089235 This article has not been copyedited and formatted. The final version may differ from this version. DMD # 89235 Non-standard ABBreviations: DMEs, drug metabolism enzymes; HLM, human liver microsomes; HLS9, -
NIH Public Access Author Manuscript Expert Opin Drug Metab Toxicol
NIH Public Access Author Manuscript Expert Opin Drug Metab Toxicol. Author manuscript; available in PMC 2009 March 19. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Expert Opin Drug Metab Toxicol. 2008 June ; 4(6): 697±720. doi:10.1517/17425250802102627. Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily Satori A Marchitti, Chad Brocker*, Dimitrios Stagos*, and Vasilis Vasiliou† University of Colorado Health Sciences Center, Molecular Toxicology & Environmental Health Sciences Program, Department of Pharmaceutical Sciences, Denver, Colorado 80262, USA Abstract Background—Aldehydes are highly reactive molecules. While several non-P450 enzyme systems participate in their metabolism, one of the most important is the aldehyde dehydrogenase (ALDH) superfamily, composed of NAD(P)+-dependent enzymes that catalyze aldehyde oxidation. Objective—This article presents a review of what is currently known about each member of the human ALDH superfamily including the pathophysiological significance of these enzymes. Methods—Relevant literature involving all members of the human ALDH family was extensively reviewed, with the primary focus on recent and novel findings. Conclusion—To date, 19 ALDH genes have been identified in the human genome and mutations in these genes and subsequent inborn errors in aldehyde metabolism are the molecular basis of several diseases, including Sjögren-Larsson syndrome, type II hyperprolinemia, γ-hydroxybutyric aciduria and pyridoxine-dependent seizures. ALDH enzymes also play important roles in embryogenesis and development, neurotransmission, oxidative stress and cancer. Finally, ALDH enzymes display multiple catalytic and non-catalytic functions including ester hydrolysis, antioxidant properties, xenobiotic bioactivation and UV light absorption. Keywords aldehyde dehydrogenase; aldehyde metabolism; ALDH 1. -
Update on the Aldehyde Dehydrogenase Gene (ALDH) Superfamily Brian Jackson,1 Chad Brocker,1 David C
GENOME UPDATE Update on the aldehyde dehydrogenase gene (ALDH) superfamily Brian Jackson,1 Chad Brocker,1 David C. Thompson,2 William Black,1 Konstandinos Vasiliou,1 Daniel W. Nebert3 and Vasilis Vasiliou1* 1Molecular Toxicology and Environmental Health Sciences Program, Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Center, Aurora, CO 80045, USA 2Department of Clinical Pharmacy, University of Colorado Anschutz Medical Center, Aurora, CO 80045, USA 3Department of Environmental Health and Center for Environmental Genetics (CEG), University of Cincinnati Medical Center, Cincinnati, OH 45267, USA *Correspondence to: Tel: þ1 303 724 3520; Fax: þ1 303 724 7266; E-mail: [email protected] Date received (in revised form): 23rd March 2011 Abstract Members of the aldehyde dehydrogenase gene (ALDH) superfamily play an important role in the enzymic detoxifi- cation of endogenous and exogenous aldehydes and in the formation of molecules that are important in cellular processes, like retinoic acid, betaine and gamma-aminobutyric acid. ALDHs exhibit additional, non-enzymic func- tions, including the capacity to bind to some hormones and other small molecules and to diminish the effects of ultraviolet irradiation in the cornea. Mutations in ALDH genes leading to defective aldehyde metabolism are the molecular basis of several diseases, including gamma-hydroxybutyric aciduria, pyridoxine-dependent seizures, Sjo¨gren–Larsson syndrome and type II hyperprolinaemia. Interestingly, several ALDH enzymes appear to be markers for normal and cancer stem cells. The superfamily is evolutionarily ancient and is represented within Archaea, Eubacteria and Eukarya taxa. Recent improvements in DNA and protein sequencing have led to the identification of many new ALDH family members.