Oxidant stress with hydrogen peroxide attenuates calcium paradox injury: Role of protein kinase C and ATP-sensitive potassium channel

Hiroshi Miyawaki, Yigang Wang, Muhammad Ashraf

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Objective: We tested the hypOtheses that low concentration of H2O2 attenuates the Ca2+ paradox (Ca2+ PD) injury, and that activation of protein kinase C (PKC) and/or ATP-sensitive potassium channel (K(ATP)) are involved in the protective effects of H2O2. Methods: Langendorff-perfused rat hearts were subjected to the Ca2+ PD (10 rain of Ca2+ depletion followed by 10 min of Ca2+ repletion). Functional and biochemical effects of H2O2 and other interventions on the cell injury induced by the Ca2+ PD were assessed. Results: In the Ca2+ PD hearts pretreated with 20 μmol/l H2O2, left ventricular end-diastolic pressure and coronary flow were significantly preserved. Furthermore, peak lactate dehydrogenase release was significantly decreased and ATP contents were more preserved, compared with non-treated Ca2+ PD hearts. H2O2-treated hearts also showed remarkable preservation of cell structure. Addition of a specific PKC inhibitor, chelerythrine during H2O2 treatment completely abolished the beneficial effects of H202 on the Ca2+ PD. Similarly, an activator of PKC, Phorbol 12-myristate 13 acetate mimicked the protection by H2O2. Furthermore, pretreatment with a K(ATP) opener, cromakalim also provided protection similar to H2O2 against the Ca2+ PD injury. However, a specific K(ATP) inhibitor, glibenclamide was not able to completely block the effects of H2O2. Conclusions: These findings suggest that pretreatment with low concentration of H2O2 provides significant protection against the lethal injury of Ca2+ PD in rat hearts. PKC-mediated signaling pathways appear to play a crucial role in the protection against the Ca2+ PD injury.

Original languageEnglish (US)
Pages (from-to)691-699
Number of pages9
JournalCardiovascular Research
Volume37
Issue number3
DOIs
StatePublished - Mar 1 1998
Externally publishedYes

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Keywords

  • Calcium
  • K(ATP) channel
  • Myocytes
  • Preconditioning
  • Protein kinase C

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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