Neonatal rat cardiomyocyte hypertrophy is induced by tumor necrosis factor-α through PI3K-IP3R-Ca2+ pathways

AIM: To investigate the role of PI3K-IP₃R-Ca²⁺ pathways in cardiomyocyte hypertrophy induced by tumor necrosis factor-α (TNF-α). METHODS: Myocardial cells of neonatal rats were cultured in vitro. The hypertrophic model was induced by TNF-α. The protein content was assayed with Lowry's method. The volumes of the cardiomyocytes were detected by computer photograph analysis system. The protein synthesis was determined by the method of[³H]-leucine incorporation.[Ca²⁺]_i transient was measured by Till image system with cell-loading Fura-2/AM. RESULTS: LY294002, a PI3K inhibitor, significantly suppressed the amplitude elevation of the spontaneous[Ca²⁺]_i transients induced by TNF-α in cultured ventricular myocytes from neonatal rats. The effect was similar to that of LY294002+2-APB (P>0.05), but lower than that in LY294002+ryanodine group (P<0.05). LY294002 significantly reduced the enhancements of protein content,[³H]-leucine incorporation and cell size induced by TNF-α. The effect was similar to that in 2-APB+LY294002 group, but higher than that in 2-APB group and lower than that in ryanodine+LY294002 group. CONCLUSION: TNF-α induces cardiac hypertrophy through PI3K-IP₃R-Ca²⁺ pathways.