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• W2123048393 abstract "Perfusion of the heart with bradykinin triggers cellular signaling events that ultimately cause opening of mitochondrial ATP-sensitive K + (mitoK ATP ) channels, increased H 2 O 2 production, inhibition of the mitochondrial permeability transition (MPT), and cardioprotection. We hypothesized that the interaction of bradykinin with its receptor induces the assembly of a caveolar signaling platform (signalosome) that contains the enzymes of the signaling pathway and that migrates to mitochondria to induce mitoK ATP channel opening. We developed a novel method for isolating and purifying signalosomes from Langendorff-perfused rat hearts treated with bradykinin. Fractions containing the signalosomes were found to open mitoK ATP channels in mitochondria isolated from untreated hearts via the activation of mitochondrial PKC-ε. mitoK ATP channel opening required signalosome-dependent phosphorylation of an outer membrane protein. Immunodetection analysis revealed the presence of the bradykinin B 2 receptor only in the fraction isolated from bradykinin-treated hearts. Immunodetection and immunogold labeling of caveolin-3, as well as sensitivity to cholesterol depletion and resistance to Triton X-100, attested to the caveolar nature of the signalosomes. Ischemic preconditioning, ischemic postconditioning, and perfusion with ouabain also led to active signalosome fractions that opened mitoK ATP channels in mitochondria from untreated hearts. These results provide initial support for a novel mechanism for signal transmission from a plasma membrane receptor to mitoK ATP channels." @default.
• W2123048393 created "2016-06-24" @default.
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• W2123048393 date "2008-09-01" @default.
• W2123048393 modified "2023-10-16" @default.
• W2123048393 title "Conditioning the heart induces formation of signalosomes that interact with mitochondria to open mitoK_ATPchannels" @default.
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• W2123048393 doi "https://doi.org/10.1152/ajpheart.00520.2008" @default.
• W2123048393 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2544503" @default.
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