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Cardioprotective effect of zinc requires ErbB2 and Akt during hypoxia/reoxygenation

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Abstract

Recent literature suggests that exogenous zinc can prevent ischemia reperfusion injury by activating phosphoinositide-3 kinase (PI3K)/Akt and by targeting the mitochondrial permeability transition pore (mPTP). It is known that ErbB2 expression promotes association and activation of PI3-kinase/Akt, resulting in growth and survival of cardiac myocytes. In this study, we found that zinc-induced ErbB2 protein expression and Akt activation are required for preventing reperfusion injury. Neonatal rat cardiac myocytes subjected to 8 h of hypoxia, followed by 16 h of reoxygenation induced cardiomyocyte apoptosis, as assessed by increased caspase-3 activity, annexin V staining and lowered MTT reduction and ATP levels. However, addition of zinc-pyrithione (ZPT) before onset of reoxygenation effectively lowered the apoptotic indices and restored the ATP levels. ZPT induced a significant increase in ErbB2 protein expression and Akt activation. Pretreatment with Hsp 90 inhibitor, geldanamycin or PI3-kinase inhibitor, wortmannin prevented the increase in ATP levels and abrogated the protective effect of zinc-pyrithione. Taken together, these data suggest that zinc prevents reperfusion injury by modulating the ErbB2 protein expression and Akt activation.

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Authors and Affiliations

  1. Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA

    Kasi Viswanath & Sreedhar Bodiga

  2. Blood Research Institute, 8701, Watertown Plank Road, Milwaukee, WI, USA

    Victor Balogun, Anita Zhang & Vijaya Lakshmi Bodiga

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  1. Kasi Viswanath
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  2. Sreedhar Bodiga
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  4. Anita Zhang
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  5. Vijaya Lakshmi Bodiga
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Correspondence to Vijaya Lakshmi Bodiga.

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Viswanath, K., Bodiga, S., Balogun, V. et al. Cardioprotective effect of zinc requires ErbB2 and Akt during hypoxia/reoxygenation. Biometals 24, 171–180 (2011). https://doi.org/10.1007/s10534-010-9371-8

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