Mycophenolic acid mediated mitochondrial membrane potential transition change lead to T lymphocyte apoptosis.
10.4174/jkss.2011.81.4.235
- Author:
Soo Jin Na CHOI
1
;
Ho Kyun LEE
;
Nam Ho KIM
;
Sang Young CHUNG
Author Information
1. Department of Surgery, Chonnam National University Medical School, Gwangju, Korea. sycpvts@chonnam.ac.kr
- Publication Type:Original Article
- Keywords:
Mycophenolic acid;
Mitochondrial membrane potential;
Apoptosis
- MeSH:
Adenosine Diphosphate Ribose;
Apoptosis;
bcl-2-Associated X Protein;
BH3 Interacting Domain Death Agonist Protein;
Blotting, Western;
Caspase 3;
Caspase 9;
Cell Survival;
Citrus sinensis;
Cytochromes c;
Cytosol;
Flow Cytometry;
Fluorescence;
Humans;
Jurkat Cells;
Lymphocytes;
Membrane Potential, Mitochondrial;
Mitochondria;
Mitochondrial Membranes;
Mycophenolic Acid;
Protein Kinase C-delta;
Proteins
- From:Journal of the Korean Surgical Society
2011;81(4):235-241
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: 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-delta (PKC-delta). 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-XL /Bcl-XS 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. CONCLUSION: These results suggest that mitochondrial dysfunction caused by MPA induces human T lymphocyte apoptosis.
