PanK4 Being An Anti-beta-cell Apoptosis Agent: A Potential Target For Diabetic Therapy

Significant increases inβ-cell apoptosis has been reported associated with Type 2 diabetes. Pantothenate kinase(PanK) as a key regulatory enzyme in the coenzyme A(CoA) biosynthetic pathway is a potential molecular target of regulatingβ-cell apoptosis in Type 2 diabetes.Here,we tested a hypothesis that rat pantothenate kinase 4(rPanK4) is an anti-β-cell apoptosis agent.To verify this hypothesis,recombinant rPanK4 was transfected in RINm5F cells(rPanK4-RINm5F) and RINm5F cells that apoptosis was induced using STZ.The apoptotic rate was found significant decreased in RINm5F cells that stable rPanK4 were expressed.Significant decrease in pro-caspase-9 mRNA expression was observed in the rPanK4-RINm5F cells.However,no significant changes were found in the transcription and translation levels of the Bcl-2,Bax,Bad,pro-caspase-3, and pro-caspase-8 genes.Similar gene expression profiles were found by doping glucose in cultural media.There was little effect of overexpressed rPanK4 in the expression of pro-caspase-3 gene and the mitochondrial function.After exposing RINm5F cells to STZ in the presence of overly expressed rPanK4,caspase-9 and caspase-3 activities in these cells were significantly suppressed.The suppression of the caspase-3 activity was also observed as a result of depression of the caspase-9 activity.These results suggest that the overexpression of rPanK4 causes partial inhibition of the apoptotic signaling by decreasing the transcriptional level of the caspase9 and subsequent inhibition of the effecter, caspases-3.