The expression of kinase CK2 in preterm newborns

Monika Wójtowicz-Marzec, PhD Janusz Kocki, Prof. Department of Clinical Genetics, Department of Medical Genetics in Lublin, Poland Neonatal Department, Department of Obstetrics Clinic and Pathology of Pregnancy in Lublin, Poland as a holoenzyme

α α

ααßß ß ß

αα Regulatory subunits α • CSNK2A1 α’ • CSNK2A2 ßß αα’ßß α’α’ßß ß • CSNK2B

αα’ α’α’ CK2: structure, regulation and role in cellular decisions of life and death David W. LITCHFIELD Casein kinase CK2- unique features 1. ubiquitous in eucariotic organism 2. conservative structure 3. over 300 substrats 4. unique ability to utilize GTP as a phosphate donor in place of ATP 5. Activity as a holoenzyme and separate subunits 6. Role in: transcription, translation, cycle, proliferation, morfogenesis, oncogenesis, apoptosis, inflamatory response, activation of viruses Aim  The aim of this study was the analysis of expression structural subunits of protein kinase CK2:  CSNK2A1, CSNK2A2, CSNK2B in preterm newborns and fullterm newborns. Material and Methods The overall group consisted of 75 patients.  25 control group (healthy full term newborns)  30 preterm newborns  20 full term newborns with disturbed neonatal period Statistical analysis was mainly focused on significant correlation between the expression of . CSNK2A1 . CSNK2A2 . CSNK2B in diagnostic groups.

All procedures were approved by Ethical Committee of Medical University of Lublin and mothers. expression was analyzed by Semiquantitative Real- Time PCR. Short version of characteristics of the analyzed groups

Control Preterm Full term [25] [30] [20]

64% girls 50% girls 50% girls

39,7 hbd 34,2 hbd 39,8 hbd

3554g [2460-4570g] 2245 g [900-3660] 3641 g[2870-4560g] 63% intrauterine 25% intrauterine infection infection 60% respiratory 10% respiratory failure failure 23% low Apgar score 10% low Apgar score at 5 min <7) at 5 min <7 13% congenital 5% congenital anomalies anomalies 20% cesarian section 19% cesarian section 10% cesarian section Mean expression of CSNK2A1, CSNK2A2, CSNK2B in control group, preterm newborns and full term newborns. CSNK2B CSNK2A1 CSNK2A2 CSNK2B CSNK2A1 CSNK2A2 CSNK2B CSNK2A1 CSNK2A2 control control control preterm preterm preterm Full term Full term Full term CSNK2B 0,8997 0,7805 -0,0978 -0,3097 -0,2225 0,2625 0,3429 0,3692 control p=0,000 p=0,003 p=0,762 p=0,327 p=0,487 p=0,410 p=0,275 p=0,238

CSNK2A1 0,8997 0,6611 -0,1090 -0,2707 -0,1323 0,1238 0,1663 0,2261 control p=0,000 p=0,019 p=0,736 p=0,395 p=0,682 p=0,701 p=0,606 p=0,480

CSNK2A2 0,7805 0,6611 0,0165 -0,2186 -0,2422 -0,1458 -0,0371 -0,0611 control p=0,003 p=0,019 p=0,959 p=0,495 p=0,448 p=0,651 p=0,909 p=0,850

CSNK2B -0,0978 -0,1090 0,0165 0,3175 0,1666 -0,0467 -0,0512 -0,0996 preterm p=0,762 p=0,736 p=0,959 p=0,315 p=0,605 p=0,885 p=0,875 p=0,758

CSNK2A1 -0,3097 -0,2707 -0,2186 0,3175 0,6718 -0,0021 -0,1668 -0,2117 preterm p=0,327 p=0,395 p=0,495 p=0,315 p=0,017 p=0,995 p=0,604 p=0,509

CSNK2A2 -0,2225 -0,1323 -0,2422 0,1666 0,6718 -0,2738 -0,1821 -0,1194 preterm p=0,487 p=0,682 p=0,448 p=0,605 p=0,017 p=0,389 p=0,571 p=0,712

CSNK2B 0,2625 0,1238 -0,1458 -0,0467 -0,0021 -0,2738 0,8125 0,7528 Full term p=0,410 p=0,701 p=0,651 p=0,885 p=0,995 p=0,389 p=0,001 p=0,005

CSNK2A1 0,3429 0,1663 -0,0371 -0,0512 -0,1668 -0,1821 0,8125 0,9840 Full term p=0,275 p=0,606 p=0,909 p=0,875 p=0,604 p=0,571 p=0,001 p=0,000

CSNK2A2 0,3692 0,2261 -0,0611 -0,0996 -0,2117 -0,1194 0,7528 0,9840 Full term p=0,238 p=0,480 p=0,850 p=0,758 p=0,509 p=0,712 p=0,005 p=0,000 Results

 This study revealed statistical significant higher expression of all structural subunits of CK2 in preterm newborns.  Worth noticing was over twofold expression of CSNK2B in each group what might to support the thesis of autonomous expression and function of regulatory β subunit protein kinase CK2 Conclusion

 This study is the first that analyses protein kinase CK2 in aspect of neonatal period and need further evaluation.  Prematurity characterizes highest expression of CK2 in comparison to full term newborns. This observation may suggest more intense phosphorylation processes in immature newborns. Overexpression of protein kinase CK2 may be also determinant of pathological processes like inflammatory response, viral infection or perinatal injury.  This results reveal protein kinase CK2 as a potent pharmacological target that may influence on pathologic processes in preterm newborns.