Dear Editor： Coenzyme A （CoA） is a primary and predominant acyl group carrier involved in a wide variety of important biochemical processes. The CoA biosynthetic pathway is composed of five enzymatic steps, of which Pantothenate kinase （PanK） is a key regulatory enzyme. The multiple isoforms of PanK are encoded by four different genes [1,2]. In our previous studies of SNP markers by genotyping the case-controlled DNAs, we found that one SNP within the hPANK4 gene on chromosome 1 was associated with type 2 diabetes [3-5]. We subsequently showed that rat PanK4 （rPanK4） was up-regulated when rats were challenged by high concentration of glucose [6]. M2-type pyruvate kinase （Pkm2） was found, both in vitro and in vivo, to be associated with rPanK4 [7]. These data suggest that PanK4 may have a role in diabetes pathogenesis. The development of type 2 diabetes is due partly to the loss of the pancreatic β-cell mass, therefore the secreted amount of insulin is insufficient to maintain the glucose homoestasis [8]. In the present study, we evaluated the effect ofrPanK4 on β-cell apoptosis. We aimed to determine the potential ofrPanK4 gene in β-cell apoptosis induced by the cytotoxic agent streptozotocin （STZ）.
Ruo Lan XiangYan Li YangJin ZuoXin Hua XiaoYong Sheng ChangFu De Fang
Peroxisome proliferator-activated receptor gamma （PPAR）,） coactivator-1 alpha （PGC-1α） coactivates multiple transcription factors and regulates several metabolic processes. The current study investigated the role of PGC-1α in the induction of apoptosis in human epithelial ovarian cancer cells. The PGC-1α mRNA level between human ovaries and human ovarian epithelial tumors was examined by quantitative RT-PCR. Less PGC- 1α expression was found in the surface epithelium of malignant tumors compared with normal ovaries. Overexpression of PGC-1α in human epithelial ovarian cancer cell line Ho-8910 induced cell apoptosis through the coordinated regulation of Bcl-2 and Bax expression. Microarray analyses confirmed that PGC-1α dramatically affected the apoptosis-related genes in Ho-8910 cells. Mitochondrial functional assay showed that the induction of apoptosis was through the terminal stage by the release of cytochrome c. Furthermore, PG-C- 1 α-induced apoptosis was partially, but not completely, blocked by PPAR）, antagonist （GW9662）, and suppression of PPAR）, expression by siRNA also inhibited PGC-1α-induced apoptosis in Ho-8910 cells. These data suggested that PGC-1α exerted its effect through a PPARγ-dependent pathway. Our findings indicated that PGC-1α was involved in the apoptotic signal transduction pathways and downregulation of PGC-1α may be a key point in promoting epithelial ovarian cancer growth and progression.
