228 research outputs found

    Expression and regulation of type 2A protein phosphatases and alpha4 signalling in cardiac health and hypertrophy

    Get PDF
    Abstract Cardiac physiology and hypertrophy are regulated by the phosphorylation status of many proteins, which is partly controlled by a poorly defined type 2A protein phosphatase-alpha4 intracellular signalling axis. Quantitative PCR analysis revealed that mRNA levels of the type 2A catalytic subunits were differentially expressed in H9c2 cardiomyocytes (PP2ACb[PP2ACa[PP4C[PP6C), NRVM (PP2ACb[PP2ACa = PP4C = PP6C), and adult rat ventricular myocytes (PP2ACa[ PP2ACb[PP6C[PP4C). Western analysis confirmed that all type 2A catalytic subunits were expressed in H9c2 cardiomyocytes; however, PP4C protein was absent in adult myocytes and only detectable following 26S proteasome inhibition. Short-term knockdown of alpha4 protein expression attenuated expression of all type 2A catalytic subunits. Pressure overload-induced left ventricular (LV) hypertrophy was associated with an increase in both PP2AC and alpha4 protein expression. Although PP6C expression was unchanged, expression of PP6C regulatory subunits (1) Sit4-associated protein 1 (SAP1) and (2) ankyrin repeat domain (ANKRD) 28 and 44 proteins was elevated, whereas SAP2 expression was reduced in hypertrophied LV tissue. Co-immunoprecipitation studies demonstrated that the interaction between alpha4 and PP2AC or PP6C subunits was either unchanged or reduced in hypertrophied LV tissue, respectively. Phosphorylation status of phospholemman (Ser63 and Ser68) was significantly increased by knockdown of PP2ACa, PP2ACb, or PP4C protein expression. DNA damage assessed by histone H2A.X phosphorylation (cH2A.X) in hypertrophied tissue remained unchanged. However, exposure of cardiomyocytes to H2O2 increased levels of cH2A.X which was unaffected by knockdown of PP6C expression, but was abolished by the short-term knockdown of alpha4 expression. This study illustrates the significance and altered activity of the type 2A protein phosphatase-alpha4 complex in healthy and hypertrophied myocardium

    The (In)Visibility of Gender in Scandinavian Climate Policy-Making

    Full text link
    © 2014 Taylor & Francis. This article explores the link between gender representation and climate policy-making in Scandinavia. We ask to what extent equal descriptive representation (critical mass) results in substantive representation (critical acts). Our study shows that women and men are equally represented in administrative and political units involved in climate policy-making, and in some units women are in the majority. However, a text analysis of the outcomes, that is, the Scandinavian climate strategies, reveals a silence regarding gender, further confirmed through interviews. Accordingly, a critical mass of women does not automatically result in gender-sensitive climate policy-making, recognizing established gender differences in material conditions and in attitudes toward climate issues. In interviews, we also note that policy-makers are largely unaware of gender differences on climate issues in the Scandinavian context. We discuss why a critical mass of women in climate policy-making has not led to critical acts and offer alternative explanations informed by feminist IR theory. For example, poststructural feminism claims that masculine norms are deeply institutionalized in climate institutions; hence, policy-makers adapt their actions to the masculinized institutional environment. Thus, substantive representation should be understood in relation to gendered institutional processes

    Phosphorylation and inactivation of protein phosphatase 1 by pp60v-src.

    No full text
    corecore