Cardioprotective 3',4'-dihydroxyflavonol attenuation of JNK and p38 MAPK signalling involves CaMKII inhibition

NR Lim; CJ Thomas; LS Silva; YY Yeap; S Yap; JR Bell; LMD Delbridge; MA Bogoyevitch; OL Woodman; SJ Williams; CN May; DCH Ng

Journal article

Cardioprotective 3',4'-dihydroxyflavonol attenuation of JNK and p38 MAPK signalling involves CaMKII inhibition

NR Lim, CJ Thomas, LS Silva, YY Yeap, S Yap, JR Bell, LMD Delbridge, MA Bogoyevitch, OL Woodman, SJ Williams, CN May, DCH Ng

Biochemical Journal | PORTLAND PRESS LTD | Published : 2013

DOI: 10.1042/BJ20121538

Abstract

DiOHF (3',4'-dihydroxyflavonol) is cardioprotective against I/R (ischaemia/reperfusion) injury. The biological activities of flavonols are associated with kinase modulation to alter cell signalling. We thus investigated the effects of DiOHF on the activation of MAPKs (mitogen-activated protein kinases) that regulate the cardiac stress response. In an ovine model of I/R, JNK (c-Jun N-terminal kinase), p38MAPK, ERK (extracellularsignal- regulated kinase) and Akt were activated, and NP202, a pro-drug of DiOHF, reduced infarct size and inhibited JNK and p38MAPK activation, whereas ERK and Akt phosphorylation were unaltered. Similarly, in cultured myoblasts, DiOHF pre-treatment preserved viabilit..

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University of Melbourne Researchers

James Bell Author

Lea Delbridge Author

Spencer Williams Author

Clive May Author

Related Projects (1)

NHMRC Research Fellowship 2009 - MAY

I am a cardiovascular physiologist investigating the origin of the large increases in cardiac and renal sympathetic nerve activity in heart ..

Grants

Funding Acknowledgements

This work was supported by grants from the National Health and Medical Research Council [grant number 628335], the National Heart Foundation of Australia [grant number G11M 6115], the Australian Research Council and an Interdisciplinary Seed Grant from the University of Melbourne, and by the Victorian Government through the Operational Infrastructure Scheme. N.R.L is a recipient of a Melbourne International Research Scholarship. J.R.B is supported by a Heart Foundation Australia Fellowship, C.N.M. is supported by a National Health and Medical Research Council Research Fellowship [grant number 5668191 and D.C.H.N. is supported by an Australian Research Council Future Fellowship [grant number FT120100193].