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S. Cheng¹, Q. Wu¹, F. Yang², M. Xu¹, M. Leski³, and G.-Q. Chen^1,3,*

¹ Dept. of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China
² Food Science College, Shenyang Agriculture University, Shenyang, Liaoning 110161, China

³ Multidisciplinary Research Center, Shantou University, Shantou, Guangdong 515063, China

Keywords: (±)-3-hydroxybutyric acid, cell proliferation, calcium influx, cell cycle

Poly(hydroxybutyrate-co-hydroxyhexanoate) (PHBHHx), a member of the polyhydroxyalkanoate (PHA) family of biopolyesters, has superior mechanical properties and biocompatibilities that enable it to meet diverse biomedical requirements. The main component of PHBHHx is (±)-3-hydroxybutyric acid (HB), a ketone body that is also produced in vivo. In the present study, we investigated the effects of HB treatment on Murine fibroblasts L929 cells, Human umbilical vein endothelial cells and Rabbit articular cartilages. HB (0.005-0.10 g/L) promoted cell proliferation for each cell line. Cell cycle analysis indicated that HB had a stimulatory effect on DNA synthesis. Flow cytometric analysis of L929 cells revealed changes in the [Ca²⁺]_i for different stages of the cell cycle. In L929 cells, HB (0.02 g/L) stimulated a rapid increase in the concentration of cytosolic calcium that was blocked by verapamil and diltiazem, inhibitors of L-type Ca²⁺-channels. Finally, verapamil inhibited HB-induced L929 cell proliferation. Collectively, these results indicate that HB has a stimulatory effect on cell cycle progression that is mediated by a signaling pathway dependent upon increases in [Ca²⁺]_i. This trophic effect may underlie the good biocompatibility observed for PHBHHx.

論文來(lái)源：International Symposium on Biological Polyesters ,Auguest 22-27, 2004