Decreased myocardial injury and improved contractility after administration of a peptide derived against the alpha-interacting domain of the L-type calcium channel.
Bottom Line: Activation of the channel also alters mitochondrial function.In search of the mechanism for the effect, we found that intracellular calcium ([Ca(2+)]i, Fura-2), superoxide production (dihydroethidium fluorescence), mitochondrial membrane potential (Ψm, JC-1 fluorescence), reduced nicotinamide adenine dinucleotide production, and flavoprotein oxidation (autofluorescence) are decreased after application of AID-TAT peptide.Application of AID-TAT peptide significantly decreased infarct size and supported contractility up to 12 weeks postcoronary artery occlusion as a result of a decrease in metabolic demand during reperfusion.
Affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, Crawley, WA, Australia (H.M.V., L.C.H.).Show MeSH
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Mentions: We have shown previously that 5 minutes of exposure of myocytes to H2O2 results in a significant further increase in superoxide assessed as changes in dihydroethidium (DHE) fluorescence in guinea pig ventricular myocytes.10,30 The further increase in superoxide occurred as a result of increased calcium uptake into mitochondria, increased reduction of NAD+, and increased electron flow into mitochondrial complex II.30 We assessed the effect of AID‐TAT peptide on DHE fluorescence in ventricular myocytes from C57BL mice. Application of 40 μmol/L of H2O2 resulted in 70.3±25.1% further increase in DHE signal that was completely attenuated with nisoldipine (Figure 4A and 4B). Application of the superoxide scavenger, N‐tert‐butyl‐α‐phenyl‐nitrone (PBN), completely abolished DHE signal, confirming specificity of the indicator for superoxide (Figure 4B, inset right). Application of 1 μmol/L of AID‐TAT peptide had no effect on the H2O2‐induced increase in DHE signal, but 10 μmol/L of AID‐TAT peptide significantly attenuated the increase in DHE signal (Figure 4C and 4D). AID‐TAT peptide had no effect on the DHE signal in the absence of H2O2, indicating that basal production of superoxide was unaffected by the peptide (Figure 4D, inset right).
Affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, Crawley, WA, Australia (H.M.V., L.C.H.).