title: Propofol attenuates hypoxia-induced apoptosis in alveolar epithelial type II cells through down-regulating hypoxia-inducible factor-1α.
abstract: To investigate the protective effect of propofol against hypoxia-induced apoptosis in alveolar epithelial type II (ATII) cells and to explore whether hypoxia-inducible factor-1α (HIF-1α) is involved in this process. Primary cultured rat ATII cells were randomly assigned to one of the following four groups, namely, Group C: treated under normoxia (21% O(2)), Group P(20): treated with propofol (20 μM) under normoxia (21% O(2)), Group H: treated under hypoxia (5% O(2)), and Group P(20)-H: pre-treated with propofol (20 μM) before hypoxia exposure (5% O(2)). Apoptosis in ATII cells was detected by Annexin V-FITC binding using FACScan. Expressions of HIF-1α and Bnip3L mRNA and protein in ATII cells were examined by quantitative real-time polymerase chain reaction and Western blotting analysis, respectively. Hypoxia exposure (Group H) significantly increased HIF-1α protein expression (P<0.01 vs. Group C) and significantly promoted apoptosis in ATII cells (P<0.01 vs. Group C). Expression of Bnip3L, a target gene of HIF-1α, was also significantly increased at both mRNA and protein levels in response to hypoxia (P<0.01 vs. Group C). Pretreatment with propofol (20 μM, Group P(20)-H) significantly decreased HIF-1α protein expression (P<0.01 vs. Group H) and significantly inhibited apoptosis in ATII cells (P<0.01 vs. Group H), accompanied by decreased expression of Bnip3L at both mRNA and protein levels (P<0.01 vs. Group H). Propofol (20 μM) can attenuate hypoxia-induced apoptosis in ATII cells and inhibit HIF-1α-hypoxia responsive element (HRE) axis involving Bnip3L, which may partly mediate the cytoprotective effects of propofol.
authors.affiliation: Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Fengyang Road 415, Shanghai 200003, China.
authors.forename: X Y
authors.initials: XY
authors.lastname: He
authors.forename: X Y
authors.initials: XY
authors.lastname: Shi
authors.forename: H B
authors.initials: HB
authors.lastname: Yuan
authors.forename: H T
authors.initials: HT
authors.lastname: Xu
authors.forename: Y K
authors.initials: YK
authors.lastname: Li
authors.forename: Z
authors.initials: Z
authors.lastname: Zou
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D000860:Hypoxia / Q000188:drug therapy* / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins; D015742:Propofol / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C505650:BNIP3 protein, rat; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D015742:Propofol