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Decreased myocardial injury and improved contractility after administration of a peptide derived against the alpha-interacting domain of the L-type calcium channel.

Viola HM, Jordan MC, Roos KP, Hool LC - J Am Heart Assoc (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, Crawley, WA, Australia (H.M.V., L.C.H.).

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AID‐TAT peptide decreases ischemia‐reperfusion (I/R) injury in hearts ex vivo. A, Representative sections from guinea pig hearts after I/R treated with 1 μmol/L of scrambled (AID(S)‐TAT) or active (AID‐TAT) peptides. Infarct size is assessed as area that did not take up nitroblue tetrazolium dye. B, Mean±SEM of infarct size expressed as percentage (%) of total left ventricular (LV) area for all hearts treated with AID(S)‐TAT or AID‐TAT as indicated. C, Creatine kinase (CK) activity of hearts treated with 1 μmol/L of scrambled (AID(S)‐TAT) or active (AID‐TAT) peptides before (Pre) and after (Post) ischemia as indicated. D, Lactate dehydrogenase (LDH) activity of hearts treated with 1 μmol/L of scrambled (AID(S)‐TAT) or active (AID‐TAT) peptides before (Pre) and after (Post) ischemia as indicated. E, GSH/GSSG ratio of hearts treated with 1 or 10 μmol/L of scrambled (AID(S)‐TAT) or active (AID‐TAT) peptides before (Pre) and after (Post) ischemia as indicated. n represents number of hearts. Statistical significance was determined using the Kruskal‐Wallis test followed by Dunn's multiple comparison test. AID indicates alpha‐interacting domain; GSH/GSSG, glutathione to oxidized glutathione; TAT, transactivator of transcription.
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fig01: AID‐TAT peptide decreases ischemia‐reperfusion (I/R) injury in hearts ex vivo. A, Representative sections from guinea pig hearts after I/R treated with 1 μmol/L of scrambled (AID(S)‐TAT) or active (AID‐TAT) peptides. Infarct size is assessed as area that did not take up nitroblue tetrazolium dye. B, Mean±SEM of infarct size expressed as percentage (%) of total left ventricular (LV) area for all hearts treated with AID(S)‐TAT or AID‐TAT as indicated. C, Creatine kinase (CK) activity of hearts treated with 1 μmol/L of scrambled (AID(S)‐TAT) or active (AID‐TAT) peptides before (Pre) and after (Post) ischemia as indicated. D, Lactate dehydrogenase (LDH) activity of hearts treated with 1 μmol/L of scrambled (AID(S)‐TAT) or active (AID‐TAT) peptides before (Pre) and after (Post) ischemia as indicated. E, GSH/GSSG ratio of hearts treated with 1 or 10 μmol/L of scrambled (AID(S)‐TAT) or active (AID‐TAT) peptides before (Pre) and after (Post) ischemia as indicated. n represents number of hearts. Statistical significance was determined using the Kruskal‐Wallis test followed by Dunn's multiple comparison test. AID indicates alpha‐interacting domain; GSH/GSSG, glutathione to oxidized glutathione; TAT, transactivator of transcription.

Mentions: We examined the effect of a single application of 1 μmol/L of AID‐TAT peptide injected into the coronaries through the aorta within 5 minutes after commencement of reperfusion in hearts exposed to 30 minutes of no‐flow ischemia on a Langendorff apparatus. In hearts exposed to active peptide, infarct size was significantly decreased, compared to hearts exposed to 1 μmol/L of scrambled peptide (AID(S)‐TAT) (Figure 1A and 1B). Release of CK (Figure 1C) and LDH (Figure 1D) was significantly less in hearts exposed to active peptide. However, the ratio of GSH/GSSG was not altered after administration of 1 μmol/L of AID‐TAT. When the concentration of the active peptide was increased to 10 μmol/L, GSH increased, suggesting an attenuation of OS (Figure 1E).


Decreased myocardial injury and improved contractility after administration of a peptide derived against the alpha-interacting domain of the L-type calcium channel.

Viola HM, Jordan MC, Roos KP, Hool LC - J Am Heart Assoc (2014)

AID‐TAT peptide decreases ischemia‐reperfusion (I/R) injury in hearts ex vivo. A, Representative sections from guinea pig hearts after I/R treated with 1 μmol/L of scrambled (AID(S)‐TAT) or active (AID‐TAT) peptides. Infarct size is assessed as area that did not take up nitroblue tetrazolium dye. B, Mean±SEM of infarct size expressed as percentage (%) of total left ventricular (LV) area for all hearts treated with AID(S)‐TAT or AID‐TAT as indicated. C, Creatine kinase (CK) activity of hearts treated with 1 μmol/L of scrambled (AID(S)‐TAT) or active (AID‐TAT) peptides before (Pre) and after (Post) ischemia as indicated. D, Lactate dehydrogenase (LDH) activity of hearts treated with 1 μmol/L of scrambled (AID(S)‐TAT) or active (AID‐TAT) peptides before (Pre) and after (Post) ischemia as indicated. E, GSH/GSSG ratio of hearts treated with 1 or 10 μmol/L of scrambled (AID(S)‐TAT) or active (AID‐TAT) peptides before (Pre) and after (Post) ischemia as indicated. n represents number of hearts. Statistical significance was determined using the Kruskal‐Wallis test followed by Dunn's multiple comparison test. AID indicates alpha‐interacting domain; GSH/GSSG, glutathione to oxidized glutathione; TAT, transactivator of transcription.
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Related In: Results  -  Collection

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fig01: AID‐TAT peptide decreases ischemia‐reperfusion (I/R) injury in hearts ex vivo. A, Representative sections from guinea pig hearts after I/R treated with 1 μmol/L of scrambled (AID(S)‐TAT) or active (AID‐TAT) peptides. Infarct size is assessed as area that did not take up nitroblue tetrazolium dye. B, Mean±SEM of infarct size expressed as percentage (%) of total left ventricular (LV) area for all hearts treated with AID(S)‐TAT or AID‐TAT as indicated. C, Creatine kinase (CK) activity of hearts treated with 1 μmol/L of scrambled (AID(S)‐TAT) or active (AID‐TAT) peptides before (Pre) and after (Post) ischemia as indicated. D, Lactate dehydrogenase (LDH) activity of hearts treated with 1 μmol/L of scrambled (AID(S)‐TAT) or active (AID‐TAT) peptides before (Pre) and after (Post) ischemia as indicated. E, GSH/GSSG ratio of hearts treated with 1 or 10 μmol/L of scrambled (AID(S)‐TAT) or active (AID‐TAT) peptides before (Pre) and after (Post) ischemia as indicated. n represents number of hearts. Statistical significance was determined using the Kruskal‐Wallis test followed by Dunn's multiple comparison test. AID indicates alpha‐interacting domain; GSH/GSSG, glutathione to oxidized glutathione; TAT, transactivator of transcription.
Mentions: We examined the effect of a single application of 1 μmol/L of AID‐TAT peptide injected into the coronaries through the aorta within 5 minutes after commencement of reperfusion in hearts exposed to 30 minutes of no‐flow ischemia on a Langendorff apparatus. In hearts exposed to active peptide, infarct size was significantly decreased, compared to hearts exposed to 1 μmol/L of scrambled peptide (AID(S)‐TAT) (Figure 1A and 1B). Release of CK (Figure 1C) and LDH (Figure 1D) was significantly less in hearts exposed to active peptide. However, the ratio of GSH/GSSG was not altered after administration of 1 μmol/L of AID‐TAT. When the concentration of the active peptide was increased to 10 μmol/L, GSH increased, suggesting an attenuation of OS (Figure 1E).

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.

View Article: PubMed Central - PubMed

Affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, Crawley, WA, Australia (H.M.V., L.C.H.).

Show MeSH
Related in: MedlinePlus