Involvement of Antiapoptotic Signals in Rat PC12 Cells Proliferation by Cyclosporin A Treatment

  • Park, Ji-Il (Department of Dental Hygiene, Gwangju Health Collage) ;
  • Lee, Guem-Sug (Dental Science Research Institute, Brain Korea 21 Project, School of Dentistry Chonnam National University) ;
  • Jeong, Yeon-Jin (Dental Science Research Institute, Brain Korea 21 Project, School of Dentistry Chonnam National University) ;
  • Kim, Byung-Kuk (Dental Science Research Institute, Brain Korea 21 Project, School of Dentistry Chonnam National University) ;
  • Kim, Jae-Hyung (Dental Science Research Institute, Brain Korea 21 Project, School of Dentistry Chonnam National University) ;
  • Lim, Hoi-Soon (Dental Science Research Institute, Brain Korea 21 Project, School of Dentistry Chonnam National University) ;
  • Kim, Sun-Hun (Dental Science Research Institute, Brain Korea 21 Project, School of Dentistry Chonnam National University) ;
  • Kim, Won-Jae (Dental Science Research Institute, Brain Korea 21 Project, School of Dentistry Chonnam National University) ;
  • Jung, Ji-Yeon (Dental Science Research Institute, Brain Korea 21 Project, School of Dentistry Chonnam National University)
  • Published : 2007.06.30

Abstract

Cyclosporin A (CsA) plays an important role in clinical medicine and basic biology as an immunosuppressant and a mitochondrial permeability blocker, respectively. It was reported that CsA has a protective role by preventing apoptosis and promoting the proliferation in severed neurons. However, the molecular mechanisms for CsA-induced neuronal cell proliferation are unclear. In this study, we examined the mechanisms underlying the CsA-induced proliferation of PC12 cells. CsA increased the viability of PC12 cells in a dose(over $0.1{\sim}10\;{\mu}M$)-and time-dependent manner. The level of ROS generation was decreased in the CsA-treated PC12 cells. Expression of Bcl-2, an antiapoptotic molecule that inhibits the release of cytochrome c from the mitochondria into the cytosol, was upregulated, whereas Bax, a proapototic molecule, was not changed in the CsA-treated PC12 cells. CsA downregulated the mRNA expression of VDAC 1 and VDAC 3, but VDAC 2 was not changed in the CsA-treated PC12 cells. The level of cytosolic cytochrome c released from the mitochondria and the caspase-3 activity were attenuated in the CsA-treated PC12 cells. These results suggest that the mitochondria-mediated apoptotic signal and Bcl-2 family may play an important role in CsA-induced proliferation in PC12 cells.

Keywords

References

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