ArticleMolecular and cellular biochemistry2007
Dual mechanism of autoregulation of protein kinase C in myocardial ischemia.
Article in Molecular and cellular biochemistry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors at 2 institutions in 1 country.
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Abstract
backgroundRecently, a dual activation mechanism of protein kinase C (PKC) in ischemia has been reported, consisting of early translocation and late expressional regulation. Moreover, autophosphorylation of the enzyme has been shown in vitro during its activation. This study aimed to show modes of late activation of PKC in myocardial ischemia in intact hearts. METHODS AND
resultsIsolated perfused hearts of male Wistar rats were used. A: To examine if the early translocation of PKC influences the late transcriptional activation, hearts were treated with the PKC-inhibitor Bisindolylmaleimid (BIS, 0.25 microM) before the onset of ischemia and then subjected to ischemia (30 min). PKC-isoform mRNA was quantified by RT-PCR. In these experiments, ischemia leads to a selective increase of mRNA specific for the isoforms PKC-delta and PKC-epsilon (163% and 168% of control, p<0.05). This ischemia-induced upregulation could be completely blocked by BIS given before the onset of ischemia. B: To test the capacity of PKC to undergo phosphorylation during ischemia, hearts were perfused with [32P]-phosphorus and then subjected to ischemia. Ischemia (30 min) induced a significant 3-fold increase of PKC phosphorylation. Stimulation of heart with the PKC-activator tetradecanoylphorbol-13-acetate (TPA) lead to a comparable phosphorylation, suggesting that ischemia leads to autophosphorylation of PKC.
conclusionIschemia activates two distinct forms of autoregulation of PKC. The expressional upregulation of PKC-delta and PKC-epsilon is dependent on early activation of the enzyme. At the same time, processes of enzyme phosphorylation occur. Both the mechanisms may contribute to enzyme activation processes beyond the classical enzyme translocation.
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