Abstract：
:The cardiovascular system is capable of robust changes in response to physiologic and pathologic stimuli through intricate signaling mechanisms. The area of metabolism has witnessed a veritable renaissance in the cardiovascular system. In particular, the post-translational β-O-linkage of N-acetylglucosamine (O-GlcNAc) to cellular proteins represents one such signaling pathway that has been implicated in the pathophysiology of cardiovascular disease. This highly dynamic protein modification may induce functional changes in proteins and regulate key cellular processes including translation, transcription, and cell death. In addition, its potential interplay with phosphorylation provides an additional layer of complexity to post-translational regulation. The hexosamine biosynthetic pathway generally requires glucose to form the nucleotide sugar, UDP-GlcNAc. Accordingly, O-GlcNAcylation may be altered in response to nutrient availability and cellular stress. Recent literature supports O-GlcNAcylation as an autoprotective response in models of acute stress (hypoxia, ischemia, oxidative stress). Models of sustained stress, such as pressure overload hypertrophy, and infarct-induced heart failure, may also require protein O-GlcNAcylation as a partial compensatory mechanism. Yet, in models of Type II diabetes, O-GlcNAcylation has been implicated in the subsequent development of vascular, and even cardiac, dysfunction. This review will address this apparent paradox and discuss the potential mechanisms of O-GlcNAc-mediated cardioprotection and cardiovascular dysfunction. This discussion will also address potential targets for pharmacologic interventions and the unique considerations related to such targets.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Dassanayaka S,Jones SPdoi
10.1016/j.pharmthera.2013.11.005subject
Has Abstractpub_date
2014-04-01 00:00:00pages
62-71issue
1eissn
0163-7258issn
1879-016Xpii
S0163-7258(13)00223-4journal_volume
142pub_type
杂志文章,评审abstract：:Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease with a high mortality rate. Genetic and biochemical studies have shown that RAS signaling mediated by KRAS plays a pivotal role in disease initiation, progression and drug resistance. RAS signaling affects several cellular processes in PDAC, includ...
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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更新日期：2003-12-01 00:00:00
