Uncoupling protein 2 modulates cell viability in adult rat cardiomyocytes.
Uncoupling protein 2 (UCP2) is an inner mitochondrial membrane proton carrier that uncouples ATP synthesis. The aim of this study was to determine whether UCP2 plays a role in survival of adult rat cardiac myocytes. We first studied the effects of UCP2 overexpression in vitro. Overexpression of UCP2 in primary cardiomyocytes led to a significant decline in ATP level and the development of acidosis but had no observable effect on cell survival. When cardiomyocytes were challenged with hypoxia-reoxygenation, cells overexpressing UCP2 survived significantly less compared with control. This finding was associated with upregulation of proapoptotic protein Bcl-2 and 19-kDa interacting protein 3 (BNIP3). Furthermore, UCP2 short interfering RNA prevented both the increase in cell death and BNIP3 expression. To examine the in vivo role of UCP2 in the heart, we used the Dahl salt-sensitive rat heart-failure model. Northern blot analysis revealed that UCP2 mRNA level was significantly upregulated in rat heart failure along with BNIP3 protein level. In conclusion, UCP2 increases sensitivity of adult rat cardiac myocytes to hypoxia-reoxygenation by way of ATP depletion and acidosis, which in turn causes accumulation of prodeath protein BNIP3.
Bodyak
Natalya
N
Cardiovascular Division, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA.
Rigor
Debra L
DL
Chen
Yee-Shiuan
YS
Han
Yuchi
Y
Bisping
Egbert
E
Pu
William T
WT
Kang
Peter M
PM
D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D005260:Female; D006973:Hypertension / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071246:Uncoupling Protein 2
D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2