7 research outputs found

    Overexpression of heat shock proteins differentially modulates protein kinase C expression in rat neonatal cardiomyocytes

    Full text link
    Previous studies have suggested that protein kinase C (PKC) is involved in heat shock protein (Hsp)ā€“mediated cardioprotection. Therefore, we wanted to determine whether overexpression of Hsps modulates PKC expression, which will give us further insight into understanding the mechanism by which Hsps and PKC interact to protect cells from stress-induced injury. Specifically, we overexpressed the inducible form of Hsp70 (Hsp70i) or Hsp90 in rat neonatal cardiomyocytes and evaluated PKCĪ“ or PKCɛ expression by immunoblotting and immunofluorescent confocal microscopy. Western analysis showed that overexpression of Hsp70i or Hsp90 decreased PKCɛ expression. However, overexpression of Hsp70i or Hsp90 did not modify PKCĪ“ expression over control levels. Overexpression of constitutively active PKCĪ“ or PKCɛ increased Hsp70i expression over control levels. The data suggest that overexpression of Hsps differentially modulates expression of PKC isoforms in rat neonatal cardiomyocytes. Furthermore, PKC may directly play a role in Hsp-mediated cardioprotection by upregulating Hsp70i expression

    5-Hydroxytryptamine Evokes Endothelial Nitric Oxide Synthase Activation in Bovine Aortic Endothelial Cell Cultures

    Full text link
    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73595/1/j.1525-1373.1999.d01-97.x.pd

    Ca 2Ļ© -Calmodulin and Janus Kinase 2 Are Required for Activation of Sodium-Proton Exchange by the G i -Coupled 5-Hydroxytryptamine 1a Receptor

    Full text link
    ABSTRACT The type 1 sodium-proton exchanger (NHE-1) is expressed ubiquitously and regulates key cellular functions, including mitogenesis, cell volume, and intracellular pH. Despite its importance, the signaling pathways that regulate NHE-1 remain incompletely defined. In this work, we present evidence that stimulation of the 5-hydroxytryptamine 1A (5-HT 1A ) receptor results in the formation of a signaling complex that includes activated Janus kinase 2 (Jak2), Ca 2Ļ© /calmodulin (CaM), and NHE-1, and which involves tyrosine phosphorylation of CaM. The signaling pathway also involves rapid agonist-induced association of CaM and NHE-1 as assessed by coimmunoprecipitation studies and by bioluminescence resonance energy transfer studies in living cells. We propose that NHE-1 is activated through this pathway: 5-HT 1A receptor 3 G i2 ā£ and/or G i3 ā£ 3 Jak2 activation 3 tyrosine phosphorylation of CaM 3 increased binding of CaM to NHE-1 3 induction of a conformational change in NHE-1 that unmasks an obscured protonsensing and/or proton-transporting region of NHE-1 3 activation of NHE-1. The G i/o -coupled 5-HT 1A receptor now joins a handful of G q -coupled receptors and hypertonic shock as upstream activators of this emerging pathway. In the course of this work, we have presented clear evidence that CaM can be activated through tyrosine phosphorylation in the absence of a significant role for elevated intracellular Ca 2Ļ© . We have also shown for the first time that the association of CaM with NHE-1 in living cells is a dynamic process

    Ca 2+

    Full text link
    corecore