Propofol enhances HO-1 expression and ameliorates hyperglycemia induced cardiomyocyte hypertrophy

Abstract

OBJECTIVE: Heme oxygenase-1(HO-1) is preferentially induced by stretch in cardiomyocytes[1], and can attenuate cardiac hypertrophy both in vivo and in vitro[2,3].High dose propofol treatment could attenuate postischemic reperfusion injury in the heart, kidney and brain partly through inducing mRNA and protein expression of HO-1.We hypothesized that propofol could ameliorate cardiomyocyte hypertrophy via the HO-1 pathway. METHODS: Primary cultured neonatal rat cardiomyocytes were exposed to a high concentration of glucose (HG, 25.5mmol/L) or normal glucose (5.5mmol/L, Control), HG in the presence of the HO-1 inducer cobalt protoporphyrin (CoPP) (10μM), the HO-1 inhibitor zinc protoporphyrin (ZnPP) (10μM), propofol (50 μM), propofol plus ZnPP or CoPP plus ZnPP, respectively, for 48 hours. Myocyte cross-sectional area was measured by immunocytochemical analysis. Myocyte protein content was determined by bicinchoninic acid assay. Reactive oxygen species (ROS) were detected by fluroescence of DCFA-DA staining. The levels of the lipid peroxidation product malondialdehyde (MDA) and superoxide dismutase (SOD) were assayed by enzyme-liked immunosorbent assay. Reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis were used to detect HO-1 gene and protein expression. RESULTS: HG caused cardiomyocyte hypertrophy, manifest as significantly increased cardiomyocyte cross-sectional area and enhanced protein production, compared with control (all p < 0.01). This was accompanied by reduced HO-1 mRNA and protein expression (P<0.01, HG vs. control) and increased ROS and MDA production. CoPP and propofol, respectively, significantly increased HO-1 expression and attenuated HG-mediated cardiomyocyte hypertrophy, and reduced ROS and MDA production (p<0.05 or p<0.01). These protective effects of propofol or CoPP were abolished by ZnPP. CONCLUSIONS: Propofol ameliorates hyperglycemia induced cardiomyocyte hypertrophy, at least in part, by increasing HO-1 expression.