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Zeng Z.,Capital Medical University | Zeng Z.,Beijing Key Laboratory of Metabolic Disorders Related Cardiovascular Diseases | Zhang H.,Capital Medical University | Lin N.,Peking University | And 11 more authors.
Journal of Pharmacological Sciences | Year: 2014

This study determined the regulatory effect of inositol 1,4,5-trisphosphate receptors (IP3Rs) on the basal Ca2+ transients in cardiomyocytes. In cultured neonatal rat ventricular myocytes (NRVMs) at different densities, we used confocal microscopy to assess the effect of IP3Rs on the endogenous spontaneous Ca2+ oscillations through specific activation of IP3Rs with myo-IP3 hexakis (butyryloxymethyl) ester (IP3BM), a membrane permeable IP3, and interference of IP3R expression with shRNA. We found that NRVMs at the monolayer state displayed coordinated Ca2+ transients with less rate, shorter duration, and higher amplitude compared to single NRVMs. In addition, monolayer NRVMs exhibited 4 or 10 times more increased Ca2+ transients in response to phenylephrine, an α-adrenergic receptor agonist, or IP3BM than single NRVMs did, while the transient pattern remained unaltered, suggesting that the sensitivity of intracellular Ca2+ response to IP3R activation is different between single and monolayer NRVMs. However, interference of IP3R expression with shRNA reduced the frequency and amplitude of the spontaneous Ca2+ fluctuates similarly in both densities of NRVMs, resembling the effects of ryanodine receptor inhibition by ryanodine or tetracaine. Our findings suggest that IP3Rs are involved, in part, in the regulation of native Ca2+ transients, in profiles of their initiation and Ca2+ release extent, in developing cardiomyocytes. In addition, caution should be paid in evaluating the behavior of Ca2+ signaling in primary cultured cardiomyocytes at different densities. © The Japanese Pharmacological Society.


Zhang H.,Capital Medical University | Zhang H.,Beijing Key Laboratory of Metabolic Disorders Related Cardiovascular Diseases | Sun Q.,Capital Medical University | Sun Q.,Beijing Key Laboratory of Metabolic Disorders Related Cardiovascular Diseases | And 19 more authors.
BioMed Research International | Year: 2014

Hyperhomocysteinemia is strongly associated with cardiovascular diseases. Previous studies have shown that phytoestrogen α -zearalanol can protect cardiovascular system from hyperhomocysteinemia and ameliorate the level of plasma total homocysteine; however, the underlying mechanisms remain to be clarified. The aim of this research is to investigate the possible molecular mechanisms involved in ameliorating the level of plasma homocysteine by α -zearalanol. By the successfully established diet-induced hyperhomocysteinemia rat models, we found that, after α -zearalanol treatment, the activity of cystathionine β -synthase, the key enzyme in homocysteine metabolism, was significantly elevated and level of nitrative stress in liver was significantly reduced. In correlation with this, results also showed a decreased nitration level of cystathionine β -synthase in liver. Together data implied that alleviation of plasma homocysteine level by phytoestrogen α -zearalanol might be related to the reduction of cystathionine β -synthase nitration. © 2014 Hui Zhang et al.

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