ABSTRACT
The aim of the study was to verify the hypothesis that NO-dependent regulation of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) gene expression can play an important role in prevention of calcium overload under the influence of detrimental factors. It was shown that 2 hours after the administration of the NO donor dinitrosyl iron complex (DNIC), the gene expression of myocardial SERCA was increased by 20% as compared to the control. In skeletal muscles, the maximum increase in SERCA expression was observed in 6 hours and amounted to 156% as compared with the initial value. Simultaneously DNIC enhanced the resistance of isolated heart and the organism as a whole to damaging effects of intracellular calcium overload induced by post-ischemic reperfusion or vigorous exercise, respectively. The results obtained confirm the existence of NO-dependent activation of SERCA expression and the important role of this mechanism in restriction of calcium overload.
Subject(s)
Calcium-Transporting ATPases/genetics , Gene Expression Regulation, Enzymologic/physiology , Iron/pharmacology , Muscle, Skeletal/enzymology , Myocardium/enzymology , Nitric Oxide Donors/pharmacology , Nitric Oxide/physiology , Nitrogen Oxides/pharmacology , Sarcoplasmic Reticulum/enzymology , Animals , Calcium/metabolism , Gene Expression Regulation, Enzymologic/drug effects , Male , Muscle, Skeletal/metabolism , Myocardium/metabolism , Nitric Oxide/blood , Rats , Rats, Wistar , Sarcoplasmic Reticulum Calcium-Transporting ATPases , Time FactorsABSTRACT
It is known that HSP70 plays an important role in the antiischaemic effect of adaptation to stress. The aim of our study was to verify the hypothesis that nitric oxide (NO) may contribute to the activation of HSP70 synthesis and to enhance thereby the resistance of organism to the ischaemic and reperfusion damages. We observed that heat shock potentiated NO production in the heart. NO formation was completely blocked by the NO synthase inhibitor N omega-nitro-L-arginine (L-NNA). L-NNA also significantly attenuated the heat shock-induced accumulation of HSP70 (by 45% in heart). Both heat shock and NO donor induced time- and concentration-dependent HSP70 synthesis in the culture of human hepatoblastoma cells Hep G2. Prior injection of NO donor (30-100 mg per rat) exerted a dose-dependent protective effect on the isolated heart in ischaemia and reperfusion within 24 hours. We suggest that NO is involved in the activation of HSP70 synthesis which can play an important role in the delayed protective effect of NO donors.
