Key Laboratory of Molecular Biology and Drug Research

Jinzhou, China

Key Laboratory of Molecular Biology and Drug Research

Jinzhou, China
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Zhang L.,Key Laboratory of Molecular Biology and Drug Research | Wang H.,Key Laboratory of Molecular Biology and Drug Research | Lu M.,Key Laboratory of Molecular Biology and Drug Research | Wu G.,Key Laboratory of Molecular Biology and Drug Research | And 3 more authors.
Experimental and Therapeutic Medicine | Year: 2012

Recent evidence suggests that κ-opioid receptor (OR) agonists and K ATP channel activation exert antihypertrophic effects on cardiac myocytes. We studied the role of K ATP channels in the antihypertrophic effects of ORs in primary cultures of neonatal rat ventricular myocytes exposed for 48 h to the α1 adrenoceptor agonist phenylephrine and the relative contributions of mitochondrial K ATP (mitoK ATP) and sarcolemmal K ATP (sarcK ATP). Furthermore, we elucidated the pathway between ORs and K ATP channels and their impact on intracellular Ca 2+ ([Ca 2+] i) transients. Hypertrophy of cardiomyocytes was characterized by increases in i) total protein content; ii) cell size and iii) [ 3H]leucine incorporation. Phenylephrine (10 μM) increased the three parameters. Trans-(±)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamid methanesulfonate salt (U50,488H), a selective κ-opioid receptor agonist, prevented phenylephrine-induced hypertrophy and [Ca 2+] i transients. The effect of U50,488H was abolished by nor-binaltorphimine, a selective κ-OR antagonist, indicating that the effect was κ-OR-mediated. The protein kinase C inhibitor chelerythrine and the K ATP channel inhibitors glibenclamide (50 μM), a nonselective K ATP antagonist, and 5-hydroxydecanoic acid (100 μM), a mitochondrial selective K ATP antagonist, reversed the antihypertrophic effect of U50,488H, and there was no significant difference between the two K ATP channel blockers. Moreover, we also determined the expression of the Kir6.2 subunits of the K ATP channel, which increased in response to U50,488H in the presence of phenylephrine, but was suppressed by chelerythrine, glibenclamide and 5-hydroxydecanoic acid. U50,488H also attenuated the elevation of [Ca 2+] i. This study suggests that K ATP, and particularly the mitochondrial K ATP, mediates the antihypertrophic effects of κ-opioid receptor stimulation via the PKC signaling pathway.


Yang J.,Key Laboratory of Molecular Biology and Drug Research | Yang J.,The First Affiliated Hospital of Liaoning Medical College | Wang H.-X.,Key Laboratory of Molecular Biology and Drug Research | Zhang Y.-J.,The First Affiliated Hospital of Liaoning Medical College | And 3 more authors.
Chinese Traditional and Herbal Drugs | Year: 2013

Objective: To investigate the protective effect of astragaloside IV (As IV) on myocardial hypertrophy induced by isoproterenol (ISO) and its mechanism. Methods: The primary cultures of neonatal rat cardiac myocytes were cultured for 48 h in vitro. The cardiac myocytes were treated with As IV, IκBα phosphorylation inhibitor BAY11-7082, and β-blockers Propranolol for 30 min, followed by 48 h incubation with ISO 10 μmol/L. The cardiomyocyte volume was measured by computer photograph analysis system. Total protein contents were assayed by the method of Bradford. RT-PCR was used to quantify the mRNA expression of ANP and TLR4; Western blotting was used to quantify the expression of TLR4, p65, and IκBα proteins; ELISA was used to quantify TNF-α and IL-6. Results: Compared with the control group, the cell size, total protein content, ANP and TLR4 mRNA, TLR4, p65, TNF-α and IL-6 were increased, and expression of IκBα protein was decreased in ISO group (P < 0.01). As IV, BAY11-7082, and Propranolol could remarkably down-regulate the over-expression of the cell size, total protein content, ANP and TLR4 mRNA, TLR4, p65, TNF-α, and IL-6, and increase the expression of IκBα protein (P < 0.05). Conclusion: As IV has the protective effect on cardiac hypertrophy induced by ISO, which is partially referring to inhibiting the TLR4/NF-κB signaling pathway and more than attenuating inflammatory effect.

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