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% O2), Group P20: treated with propofol (20μM) under normoxia (21% O2), Group H: treated under hypoxia (5% O2), and Group P20–H: pre-treated with propofol (20μM) before hypoxia exposure (5% O2). 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 (20μM, Group P20–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 (20μM) 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.