Journal article

Fine-tuning the cardiac O-GlcNAcylation regulatory enzymes governs the functional and structural phenotype of the diabetic heart

Darnel Prakoso, Shiang Y Lim, Jeffrey R Erickson, Rachel S Wallace, Jarmon G Lees, Mitchel Tate, Helen Kiriazis, Daniel G Donner, Darren C Henstridge, Jonathan R Davey, Hongwei Qian, Minh Deo, Laura J Parry, Amy J Davidoff, Paul Gregorevic, John C Chatham, Miles J De Blasio, Rebecca H Ritchie



AIMS: The glucose-driven enzymatic modification of myocardial proteins by the sugar moiety, β-N-acetylglucosamine (O-GlcNAc), is increased in pre-clinical models of diabetes, implicating protein O-GlcNAc modification in diabetes-induced heart failure. Our aim was to specifically examine cardiac manipulation of the two regulatory enzymes of this process on the cardiac phenotype, in the presence and absence of diabetes, utilising cardiac-targeted recombinant-adeno-associated viral-vector-6 (rAAV6)-mediated gene delivery. METHODS AND RESULTS: In human myocardium, total protein O-GlcNAc modification was elevated in diabetic relative to non-diabetic patients, and correlated with left ventricular ..

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Awarded by National Health and Medical Research Council (NHMRC) of Australia

Awarded by Diabetes Australia

Awarded by NHMRC

Awarded by Health Research Council of New Zealand Project Grant

Funding Acknowledgements

This work was supported by a Project Grant to R.H.R. and M.J.D. from the National Health and Medical Research Council (NHMRC, APP1158013) of Australia, a grant to R.H.R. from Diabetes Australia (Y18G-RITR), Senior Research Fellowships from the NHMRC to R.H.R. (ID1059960) and P.G. (ID1046782), and in part by an infrastructure grant from the Victorian government of Australia. S.Y.L. and J.L. are supported by Stafford Fox Medical Research Foundation. J.R.E. is supported by a Health Research Council of New Zealand Project Grant (15/331). D.P. was supported by the University of Melbourne MIRS (Melbourne International Research Scholarship), MIFRS (Melbourne International Fee Remission Scholarship) and The Albert Shimmins Writing Up Fund.