Critical role of insulin-like growth factor binding protein-5 in methamphetamine-induced apoptosis in cardiomyocytes

Methamphetamine (MA) is a highly abused amphetamine-like psychostimulant. At present, the mechanisms underlying MA-induced cardiotoxicity are poorly understood. The cardiotoxic effects have yet not been clearly elucidated with respect to the apoptotic pathway. Insulin-like growth factor binding protein-5 (IGFBP5) is important for cell growth control and the induction of apoptosis. The aim of the present study was to analyze whether IGFBP5 is involved in MA-induced apoptosis as a novel target. MA-induced apoptosis was observed in neonatal rat ventricular myocytes (NRVMs) in a concentration-dependent manner using a terminal deoxyribonucleotide transferase-mediated dUTP nick end-labeling assay. Using reverse transcription polymerase chain reaction and western blotting, MA was demonstrated to induce concentration-dependent increases in the expression of IGFBP5. Silencing IGFBP5 with small interfering RNA significantly reduced apoptosis and suppressed the expression of caspase-3 in NRVMs following treatment with MA. To the best of our knowledge, the present study provided the first evidence suggesting that IGFBP5 is a potential therapeutic target in MA-induced apoptosis in vitro, providing a foundation for future in vivo studies.