BNIP3 Implicates in Lovastatin-induced Cell Apoptosis in Macrophage.

• Main Authors: LIN, YI-HSIU, 林逸修
• Other Authors: Shye-Jye Tang
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/05876438307427102310

碩士 === 國立臺灣海洋大學 === 生物科技研究所 === 97 === Lovastatin, the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, has been used successfully in the treatment of hypercholesterolemia for more than a decade. However, statins are powerful drugs for lowering cholesterol levels in blood now. BNIP3 (Bcl-2/E1B 19 kDa interacting protein) is a BH-3-only Bcl-2 family member, which regulates cell apoptosis or survival. When BNIP3 over-expression, it forms homodimers and locates on the mitochondrial outer membrane, induces mitochondrial dysfunction and cell apoptosis. Macrophages play an important role in immune response. We demonstrated a novel pathway. Lovastatin enhances ROS level via inhibition of HMG-CoA reductase activity in mouse macrophages, and promotes BNIP3 over-expression via enhancement of ROS level. In lovastatin-stimulated cells which pre-treated NAC reduced BNIP3 expression and apoptosis. We over-expressed BNIP3 and analyzed by Mitocapture and Rhodamine 123. Results suggested BNIP3 locate on the mitochondrial outer membrane, promoted mitochondrial aggregation, loss of mitochondrial membrane potential, MPTP (mitochondrial permeability transition pore ) opening and mitochondrial dysfunction. We analyzed lovastatin-treated cells with APOPercentage, Hoechst 33342 and PI stain. Lovastatin induced the transfer of PS ( phophatidylserine ) to the outside membrane, chromatin condensation, DNA fragmentation and apoptosis. These results demonstrated that Lovastatin induced BNIP3 over-expression via enhancement of ROS level, promoted mitochondrial dysfunction and apoptosis in macrophages.