title: Propofol Suppressed Hypoxia/Reoxygenation-Induced Apoptosis in HBVSMC by Regulation of the Expression of Bcl-2, Bax, Caspase3, Kir6.1, and p-JNK.
abstract: Recent studies have found that propofol may protect brain from cerebral ischemic-reperfusion injury. However, the underlying mechanism remains unclear. The effects of propofol were evaluated in HBVSMC after hypoxia/reoxygenation (H/R). Cell viability and levels of SOD, LDH, and MDA were measured. Apoptosis was detected by flow cytometry. The levels of Bax, Bcl-2, Caspase3, Sur2b, Kir6.1, JNK, p-JNK, mTOR, and p-mTOR proteins were measured by western blotting. H/R decreased cell viability and SOD activity and increased LDH leakage and MDA content in HBVSMC, all of which were significantly reversed by propofol. Propofol suppressed the levels of H/R-induced apoptosis. The expression of Bcl-2 and p-mTOR was significantly downregulated and the expression levels of Bax, Caspase3, Kir6.1, and p-JNK were upregulated following H/R injury. The ratio of p-JNK/JNK was increased; however, that of p-mTOR/mTOR decreased correspondingly. The effects on the expression of these proteins were reversed by propofol treatment. SP600125 enhanced and Everolimus attenuated the effect of propofol. These findings suggested that the protective effect of propofol against H/R injury in the HBVSMC was through the inhibition of apoptosis by inducing the expression of Bcl-2 and p-mTOR as well as inhibiting the expression levels of Bax, Caspase3, Kir6.1, and p-JNK.
authors.affiliation: Department of Anesthesiology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, China.
authors.forename: Jianhai
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Shanghai International Medical Center, Shanghai 201318, China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Anesthesiology, International Peace Maternal and Child Health Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Zifeng
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Deng
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D000068338:Everolimus / Q000494:pharmacology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D054086:KATP Channels / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008315:Malondialdehyde / Q000032:analysis / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013482:Superoxide Dismutase / Q000032:analysis / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000873:Anthracenes; D054086:KATP Channels; D019253:Proto-Oncogene Proteins c-bcl-2; D014404:Tubulin; D051028:bcl-2-Associated X Protein; C092520:uK-ATP-1 potassium channel; C432165:pyrazolanthrone; D008315:Malondialdehyde; D000068338:Everolimus; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3; D010100:Oxygen; D015742:Propofol