Abstract：
:1. Skeletal muscle oxidative function and metabolic gene expression are co-ordinately downregulated in metabolic diseases such as insulin resistance, obesity and Type 2 diabetes. Altering skeletal muscle metabolic gene expression to favour enhanced energy expenditure is considered a potential therapy to combat these diseases. 2. Histone deacetylases (HDACs) are chromatin-remodelling enzymes that repress gene expression. It has been shown that HDAC4 and 5 co-operatively regulate a number of genes involved in various aspects of metabolism. Understanding how HDACs are regulated provides insights into the mechanisms regulating skeletal muscle metabolic gene expression. 3. Multiple kinases control phosphorylation-dependent nuclear export of HDACs, rendering them unable to repress transcription. We have found a major role for the AMP-activated protein kinase (AMPK) in response to energetic stress, yet metabolic gene expression is maintained in the absence of AMPK activity. Preliminary evidence suggests a potential role for protein kinase D, also a Class IIa HDAC kinase, in this response. 4. The HDACs are also regulated by ubiquitin-mediated proteasomal degradation, although the exact mediators of this process have not been identified. 5. Because HDACs appear to be critical regulators of skeletal muscle metabolic gene expression, HDAC inhibition could be an effective therapy to treat metabolic diseases. 6. Together, these data show that HDAC4 and 5 are critical regulators of metabolic gene expression and that understanding their regulation could provide a number of points of intervention for therapies designed to treat metabolic diseases, such as insulin resistance, obesity and Type 2 diabetes.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
McGee SL,Hargreaves Mdoi
10.1111/j.1440-1681.2009.05311.xsubject
Has Abstractpub_date
2010-03-01 00:00:00pages
392-6issue
3eissn
0305-1870issn
1440-1681pii
CEP5311journal_volume
37pub_type
杂志文章,评审abstract：:The P2X7 receptor is a ligand-gated purinergic receptor activated by extracellular ATP. The receptor is highly expressed in immune cells and in the brain, and, upon activation, the P2X7 receptor allows a cation flux, leading to the distinct activation of intracellular signalling pathways as the secretion of pro-inflam...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,评审
doi：10.1111/1440-1681.13079
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pub_type： 杂志文章
doi：10.1111/1440-1681.13234
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pub_type： 杂志文章
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journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,评审
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pub_type： 杂志文章
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pub_type： 杂志文章
doi：10.1111/1440-1681.12961
更新日期：2018-05-07 00:00:00
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pub_type： 杂志文章,评审
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更新日期：2001-03-01 00:00:00
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journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
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更新日期：1991-05-01 00:00:00
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doi：10.1111/1440-1681.12408
更新日期：2015-06-01 00:00:00
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journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,评审
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更新日期：2000-01-01 00:00:00
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journal_title：Clinical and experimental pharmacology & physiology
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journal_title：Clinical and experimental pharmacology & physiology
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journal_title：Clinical and experimental pharmacology & physiology
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journal_title：Clinical and experimental pharmacology & physiology
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更新日期：2020-04-01 00:00:00
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journal_title：Clinical and experimental pharmacology & physiology
pub_type： 信件
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更新日期：2017-11-01 00:00:00
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journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
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更新日期：1993-12-01 00:00:00
