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REDOX REGULATION OF ISCHEMIC PRECONDITIONING IS MEDIATED BY THE DIFFERENTIAL ACTIVATION OF CAVEOLIN‐1 AND CAVEOLIN‐3 AND THEIR ASSOCIATION WITH GLUT‐4
Author(s) -
Penumathsa Suresh Varma,
Koneru Srikanth,
Thirunavukkarasu Mahesh,
Samuel Samson Mathews,
Zhan Lijun,
Maulik Gautam,
Das Dipak K,
Maulik Nilanjana
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a446
Subject(s) - cardioprotection , glut4 , enos , chromosomal translocation , protein kinase b , chemistry , ischemic preconditioning , caveolin 1 , caveolin , pharmacology , medicine , ischemia , microbiology and biotechnology , signal transduction , caveolae , biology , nitric oxide , biochemistry , nitric oxide synthase , gene
Reactive oxygen species (ROS) generated during ischemia (I) / reperfusion (R) enhances myocardial injury, but brief periods of myocardial I followed by R {(ischemic preconditioning) IP} induce cardioprotection. Myocardial I is reported to stimulate glucose uptake through the translocation of Glut‐4 from the intracellular vesicles to sarcolemma. The present study is aimed to determine IP mediated Glut‐4 translocation & association with caveolar paradox. The rats were assigned as Control Sham, IR, IP+ IR & IPN [N=n‐acetyl cysteine]. N was used as a negative effector of preconditioning mediated cardioprotection. The myocardium was preconditioned & followed by 30 min of I & 3, 24, 48 hr of R depending on protocol. Real time PCR results have shown increased expression of Glut4 and Cav3 in IP compared to other groups. Isolated lipid raft fractions in IP demonstrated increased expression of Glut4, Cav3, p‐eNOS, p‐AKT & decreased expression of Cav1 compared to IR. Significant association of Glut4 & Cav3 was observed in IP compared to IR & was abolished in IPN by N. This study documents significant role of ROS signaling in Akt / eNOS / Cav3 mediated Glut4 translocation in IP myocardium. In conclusion, our study demonstrated a novel redox mechanism in IP induced Glut4 translocation & its regulation by caveolar / Akt / eNOS status in making the heart euglycemic leading to myocardial protection in a clinically relevant ischemic model.