caa a22 4500 445321156 CHVBK 20180317142704.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s10534-010-9371-8 doi (NATIONALLICENCE)springer-10.1007/s10534-010-9371-8 Cardioprotective effect of zinc requires ErbB2 and Akt during hypoxia/reoxygenation [Elektronische Daten] [Kasi Viswanath, Sreedhar Bodiga, Victor Balogun, Anita Zhang, Vijaya Bodiga] 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 8h of hypoxia, followed by 16h 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. Springer Science+Business Media, LLC., 2010 Zinc nationallicence Cardiomyocytes nationallicence Hypoxia nationallicence Reoxygenation nationallicence ErbB2 nationallicence Akt nationallicence Hsp90 nationallicence Viswanath Kasi Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA aut Bodiga Sreedhar Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA aut Balogun Victor Blood Research Institute, 8701, Watertown Plank Road, Milwaukee, WI, USA aut Zhang Anita Blood Research Institute, 8701, Watertown Plank Road, Milwaukee, WI, USA aut Bodiga Vijaya Blood Research Institute, 8701, Watertown Plank Road, Milwaukee, WI, USA aut BioMetals Springer Netherlands 24/1(2011-02-01), 171-180 0966-0844 24:1<171 2011 24 10534 https://doi.org/10.1007/s10534-010-9371-8 text/html Onlinezugriff via DOI 1 brief-communication jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10534-010-9371-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Viswanath Kasi Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA aut NATIONALLICENCE 700 1- Bodiga Sreedhar Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA aut NATIONALLICENCE 700 1- Balogun Victor Blood Research Institute, 8701, Watertown Plank Road, Milwaukee, WI, USA aut NATIONALLICENCE 700 1- Zhang Anita Blood Research Institute, 8701, Watertown Plank Road, Milwaukee, WI, USA aut NATIONALLICENCE 700 1- Bodiga Vijaya Blood Research Institute, 8701, Watertown Plank Road, Milwaukee, WI, USA aut NATIONALLICENCE 773 0- BioMetals Springer Netherlands 24/1(2011-02-01), 171-180 0966-0844 24:1<171 2011 24 10534 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer