title: Mycophenolic acid mediated mitochondrial membrane potential transition change lead to T lymphocyte apoptosis.
abstract: OBJECTIVE
  This study demonstrated that apoptosis induced by mycophenolic acid (MPA) is mediated by mitochondrial membrane potential transition (MPT) changes in Jurkat cells.
  
  
  METHODS
  Cell viability and MPT changes were measured by flow cytometry. Western blotting was performed to evaluate the expression of Bcl-2 family proteins, Bid, truncated Bid (tBid), cytochrome c, voltage dependent anion channel (VDAC), poly ADP-ribose polymerase (PARP), and protein kinase C-δ (PKC-δ). The catalytic activity of caspase-9 and -3 was also measured.
  
  
  RESULTS
  Cell viability was decreased in time- and dose-dependent manners. Bcl-2 protein expression was decreased, but Bax protein expression was identified. A decreased Bcl-X(L) /Bcl-X(S) ratio was also noted. The expression of tBid protein also increased in a time-dependent manner in Jurkat cells treated with MPA. While normal MPT appeared as orange fluorescence, abnormal MPT corresponded to green fluorescence. Green fluorescence increased as orange decreased in the MPA-treated cells. Significantly increased concentrations of MPA induced the release of cytosolic cytochrome c. MPA also augmented the catalytic activity of caspase-9 and caspase-3 in Jurkat cells. Our findings demonstrated that MPA-induced apoptosis is mediated by MPT changes accompanied by decreased Bcl-XL expression and the appearance of tBid protein. The release of cytosolic cytochrome c from mitochondria and increased catalytic activity of caspase-9 and caspase-3 were observed in MPA-treated Jurkat cells.
  
  
  CONCLUSIONS
  These results suggest that mitochondrial dysfunction caused by MPA induces human T lymphocyte apoptosis.
authors: Department of Surgery, Chonnam National University Medical School, Gwangju, Korea.
authors: Soo Jin Na
authors: SJ
authors: Choi
authors: Ho Kyun
authors: HK
authors: Lee
authors: Nam Ho
authors: NH
authors: Kim
authors: Sang Young
authors: SY
authors: Chung