ABSTRACT
Aim To study the protective effects of SEP on the hypertrophic myocardial cells induced with high glucose and high insulin and the mechanism. Methods The protein content was assayed with Lowrys meth-od;the cardiomyocytes area was measured by computer photograph analysis system;the expression of ANF and PPAR-α was determined by RT-PCR;APS was select-ed as control drug. Results Compared with conctrol group,the protein content,cardiomyocytes area and the expression of ANF and PPAR-α of high glucose and high insulin group were significantly increased. Com-pared with conctrol group,the SEP of different dosages were able to decrease the protein content, area, the expression of ANF mRNA and PPAR-α mRNA of cul-tured hypertrophic myocadial cells induced with high glucose and high insulin. Conclusion SEP can pre-vent cardiomyocyte hypertrophy induced by high glu-cose and high insulin, which is related to its inhibition on PPAR-α signaling path.
ABSTRACT
AIM: To study the role of peroxisome proliferator-activated receptor-α (PPAR-α) signal transduction pathway in cardiac hypertrophy induced by high glucose and insulin (HGI). METHODS: The cultured neonatal rat cardiomyocytes were used to observe the effect of fenofibrate (FF), a selective PPAR-α agonist, on cardiomyocyte hypertrophy induced by HGI (glucose at concentration of 25.5 mmol/L and insulin at 0.1 μmol/L). The cardiomyocyte hypertrophic responses were assayed by measuring the cell surface area, protein content, and mRNA expression of atrial natriuretic factor (ANF). The expressions of mRNA and protein were assayed by real -time PCR and Western blotting. RESULTS: In cultured cardiomyocytes, HGI induced profound change of hypertrophic morphology, the significant increase in cell surface area, protein content and ANF mRNA expression compared to those in vehicle control (P<0.01), but the expressions of PPAR-α mRNA and protein decreased significantly (P<0.05). At the same time, the expression of cyclooxygenase 2 (COX-2), one of the PPAR-α downstream effectors was obviously elevated (P<0.05). However, FF (0.1, 0.3 and 1 μmol/L) inhibited the cardiomyocyte hypertrophy induced by HGI in a concentration-dependent manner (P<0.01). FF at concentration of 0.3 μmol/L increased the expressions of PPAR-α in both mRNA and protein levels (P<0.05) and inhibited the expressions of COX-2 (P<0.05), which were abolished by MK 886 (0.3 μmol/L), a selective PPAR-α antagonist (P<0.05). CONCLUSION: PPAR-α signal transduction pathway and its downstream effector COX-2 might involve in the cardiomyocyte hypertrophy induced by HGI.
ABSTRACT
AIM:To study the role of peroxisome proliferator-activated receptor-? (PPAR-?) signal transduction pathway in cardiac hypertrophy induced by high glucose and insulin (HGI). METHODS:The cultured neonatal rat cardiomyocytes were used to observe the effect of fenofibrate (FF),a selective PPAR-? agonist,on cardiomyocyte hypertrophy induced by HGI (glucose at concentration of 25.5 mmol/L and insulin at 0.1 ?mol/L). The cardiomyocyte hypertrophic responses were assayed by measuring the cell surface area,protein content,and mRNA expression of atrial natriuretic factor (ANF). The expressions of mRNA and protein were assayed by real -time PCR and Western blotting. RESULTS:In cultured cardiomyocytes,HGI induced profound change of hypertrophic morphology,the significant increase in cell surface area,protein content and ANF mRNA expression compared to those in vehicle control (P