期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 302, 期 10, 页码 H2122-H2130出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00775.2011
关键词
nuclear factor of activated t cells; transverse aortic constriction
资金
- National Heart, Lung, and Blood Institute (NHLBI) [R01 HL-083320, R01 HL-094419, P01 HL-078825, R01 HL-099014]
- American Heart Association National Center [0535270N]
- National Center for Research Resources (NCRR) [P20 RR-024489]
- Kentucky Science and Engineering Foundation [KSEF-1677-RDE-011]
- Veterans' Administration
- American Heart Association [0835456N]
Facundo HT, Brainard RE, Watson LJ, Ngoh GA, Hamid T, Prabhu SD, Jones SP. O-GlcNAc signaling is essential for NFAT-mediated transcriptional reprogramming during cardiomyocyte hypertrophy. Am J Physiol Heart Circ Physiol 302: H2122-H2130, 2012. First published March 9, 2012; doi: 10.1152/ajpheart.00775.2011.The regulation of cardiomyocyte hypertrophy is a complex interplay among many known and unknown processes. One specific pathway involves the phosphatase calcineurin, which regulates nuclear translocation of the essential cardiac hypertrophy transcription factor, nuclear factor of activated T-cells (NFAT). Although metabolic dysregulation is frequently described during cardiac hypertrophy, limited insights exist regarding various accessory pathways. One metabolically derived signal, beta-O-linked N-acetylglucosamine (O-GlcNAc), has emerged as a highly dynamic posttranslational modification of serine and threonine residues regulating physiological and stress processes. Given the metabolic dysregulation during hypertrophy, we hypothesized that NFAT activation is dependent on O-GlcNAc signaling. Pressure overload-induced hypertrophy (via transverse aortic constriction) in mice or treatment of neonatal rat cardiac myocytes with phenylephrine significantly enhanced global O-GlcNAc signaling. NFAT-luciferase reporter activity revealed O-GlcNAc-dependent NFAT activation during hypertrophy. Reversal of enhanced O-GlcNAc signaling blunted cardiomyocyte NFAT-induced changes during hypertrophy. Taken together, these results demonstrate a critical role of O-GlcNAc signaling in NFAT activation during hypertrophy and provide evidence that O-GlcNAc signaling is coordinated with the onset and progression of cardiac hypertrophy. This represents a potentially significant and novel mechanism of cardiac hypertrophy, which may be of particular interest in future in vivo studies of hypertrophy.
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