Interleukin-27, a novel cytokine induced by ischemia-reperfusion injury in rat hearts, mediates cardioprotective effects via the gp130/STAT3 pathway.

Patients with coronary artery disease show high serum levels of interleukin (IL)-27, a novel member of the IL-6 family. However, the function of IL-27 in hearts suffering ischemia/reperfusion (IR) injury is unclear. Here, we showed increased expression of mRNA for the IL-27 subunits, EBI3 and p28, in rat hearts after 40 min of coronary ligation and release for 7 days.

Endothelin receptor blockade ameliorates renal injury by inhibition of RhoA/Rho-kinase signalling in deoxycorticosterone acetate-salt hypertensive rats.

Purpose Of Review: Excessive production of fibrosis is a feature of hypertension-induced renal injury. Activation of RhoA/Rho-kinase (ROCK) axis has been shown in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. We assessed whether selective endothelin receptor blockers can attenuate renal fibrosis by inhibiting RhoA/ROCK axis in DOCA-salt rats.

HYS-32, a novel analogue of combretastatin A-4, enhances connexin43 expression and gap junction intercellular communication in rat astrocytes.

HYS-32 [4-(3,4-dimethoxyphenyl)-3-(naphthalen-2-yl)-2(5H)-furanone] is a new analogue of the anti-tumor compound combretastatin A-4 containing a cis-stilbene moiety. In this study, we investigated its effects on Cx43 gap junction intercellular communication (GJIC) and the signaling pathway involved in rat primary astrocytes. Western blot analyses showed that HYS-32 dose- and time-dependently upregulated Cx43 expression.

Effect of sildenafil on ventricular arrhythmias in post-infarcted rat hearts.

We have demonstrated that activation of ATP-sensitive potassium (K(ATP)) channels can attenuate sympathetic hyperinnervation. Sildenafil, a phosphodiesterase-5 inhibitor, has been shown to provide a preconditioning-like cardioprotective effect via opening of K(ATP) channels. The aim of this study was to investigate whether chronic administration of sildenafil attenuates cardiac sympathetic hyperinnervation after myocardial infarction through activation of K(ATP) channels and to compare it with the nitric oxide donor isosorbide dinitrate.

Angiotensin II and the ERK pathway mediate the induction of myocardin by hypoxia in cultured rat neonatal cardiomyocytes.

Hypoxic injury to cardiomyocytes is a stress that causes cardiac pathology through cardiac-restricted gene expression. SRF (serum-response factor) and myocardin are important for cardiomyocyte growth and differentiation in response to myocardial injuries. Previous studies have indicated that AngII (angiotensin II) stimulates both myocardin expression and cardiomyocyte hypertrophy.

The interaction of estrogen receptor alpha and caveolin-3 regulates connexin43 phosphorylation in metabolic inhibition-treated rat cardiomyocytes.

Caveolin-3, the major caveolin isoform in cardiomyocytes, plays an important role in the rapid signaling pathways initiated by stimulation of the membrane-associated molecules. To examine the role of caveolin-3 in regulating estrogen receptor alpha in cardiomyocytes, we investigate whether the membrane estrogen receptor alpha associates with caveolin-3 and whether this association is linked to the 17beta-estradiol-mediated signals. In control cardiomyocytes, following discontinuous sucrose gradient centrifugation, caveolin-3 was found predominantly in the lipid raft buoyant fractions, whereas it was distributed to both the buoyant and non-lipid raft heavy fractions following metabolic inhibition treatment.

Effects of 18-glycyrrhetinic acid on serine 368 phosphorylation of connexin43 in rat neonatal cardiomyocytes.

18Beta-glycyrrhetinic acid (18beta-GA) regulates serine/threonine dephosphorylation of connexin43 (Cx43). Phospho-specific antibodies were used here to determine the effect of 18beta-GA on serine 368-phosphorylated Cx43 (pSer368Cx43) in cultured rat neonatal cardiomyocytes by immunofluorescence microscopy and immunoblot analyses. 18beta-GA caused a time-dependent increase in pSer368Cx43 levels and induced gap junction disassembly, shown by a change in pSer368Cx43 immunostaining from large aggregates to dispersed punctates at cell-cell contact areas.

18beta-glycyrrhetinic acid promotes src interaction with connexin43 in rat cardiomyocytes.

The mechanism by which 18beta-glycyrrhetinic acid regulates gap junction intercellular communication (GJIC) remains poorly understood. In this study, treatment of cultured rat neonatal cardiomyocytes with 18beta-glycyrrhetinic acid resulted in dose-dependent inhibition of GJIC as assessed by fluorescent dye transfer analysis. 18beta-Glycyrrhetinic acid induced time-dependent serine/threonine dephosphorylation and redistribution of connexin43 (Cx43) in cardiomyocytes and the induced Cx43 dephosphorylation was prevented by the protein phosphatase inhibitor, calyculin A.

17beta-estradiol reduces the effect of metabolic inhibition on gap junction intercellular communication in rat cardiomyocytes via the estrogen receptor.

The effects of 17beta-estradiol (E2) on gap junction intercellular communication (GJIC) were assessed by Lucifer yellow dye coupling in cultured neonatal rat cardiomyocytes after metabolic inhibition (MI) using potassium cyanide and sodium iodoacetate. MI significantly reduced dye coupling of cardiomyocytes to 8.5% +/- 0.

Role of catenins in the development of gap junctions in rat cardiomyocytes.

Gap junctions are intercellular communicating channels responsible for the synchronized activity of cardiomyocytes. Recent studies have shown that the membrane-associated guanylate kinase protein, zonula occludens-1 (ZO-1) can bind to catenins in epithelial cells and act as an adapter for the transport of the connexin isotype, Cx43 during gap junction formation. The significance of catenins in the development of gap junctions and whether complexes between catenins and ZO-1 are formed in cardiomyocytes are not clear.

Role of N-cadherin- and integrin-based costameres in the development of rat cardiomyocytes.

Costameres, vinculin-containing structures found in skeletal and cardiac muscle, are thought to anchor the Z-discs of the peripheral myofibrils to the sarcolemma. Several lines of evidence indicate that two different sets of costameres, integrin- and N-cadherin-based, are present in cardiac muscles. In this study, immunoblot analysis was used to study the expression of N-cadherin, alpha-catenin, beta-catenin, vinculin, talin, and laminin in rat cardiac muscles at embryonic days 15 and 19, the day of birth (postnatal day 0), postnatal weeks 1, 2, 3, and 4, and in the adult.