TAILIEUCHUNG - Báo cáo khoa học: Diverging regulation of pyruvate dehydrogenase kinase isoform gene expression in cultured human muscle cells

The pyruvate dehydrogenase complex occupies a central and strategic posi-tion in muscle intermediary metabolism and is primarily regulated by phos-phorylation⁄dephosphorylation. The identification of multiple isoforms of pyruvate dehydrogenase kinase (PDK1–4) and pyruvate dehydrogenase phosphatase (PDP1–2) has raised intriguing new possibilities for chronic pyruvate dehydrogenase complex control. | iFEBS Journal Diverging regulation of pyruvate dehydrogenase kinase isoform gene expression in cultured human muscle cells Emily L. Abbot1 James G. McCormack2 Christine Reynet2 David G. Hassall3 Kevin W. Buchan and Stephen J. Yeaman1 1 Institute for Celland Molecular Biosciences University of Newcastle upon Tyne UK 2 Prosidion Ltd Oxford UK 3 GlaxoSmithKline Stevenage UK Keywords gene regulation mitochondria peroxisome proliferator-activated receptor pyruvate dehydrogenase kinase skeletalmuscle Correspondence . Yeaman The Institute for Celland Molecular Biosciences Faculty of Medical Sciences University of Newcastle upon Tyne Newcastle upon Tyne NE2 4HH UK Fax 44 191 222 7424 Tel 44 191 222 7433 E-mail Present address GE Healthcare Amersham UK Received 7 January 2005 revised 21 March 2005 accepted 8 April 2005 doi The pyruvate dehydrogenase complex occupies a central and strategic position in muscle intermediary metabolism and is primarily regulated by phos-phorylation dephosphorylation. The identification of multiple isoforms of pyruvate dehydrogenase kinase PDK1-4 and pyruvate dehydrogenase phosphatase PDP1-2 has raised intriguing new possibilities for chronic pyruvate dehydrogenase complex control. Experiments to date suggest that PDK4 is the major isoenzyme responsible for changes in pyruvate dehydrogenase complex activity in response to various different metabolic conditions. Using a cultured human skeletal muscle cell model system we found that expression of both PDK2 and PDK4 mRNA is upregulated in response to glucose deprivation and fatty acid supplementation the effects of which are reversed by insulin treatment. In addition insulin directly downregulates PDK2 and PDK4 mRNA transcript abundance via a phosphatidylinositol 3-kinase-dependent pathway which may involve glycogen synthase kinase-3 but does not utilize the mammalian target of rapamycin or mitogen-activated protein kinase signalling .

• Báo cáo khoa học
• Report medicine
• traditional medicine
• scientific reports
• oxidation
• chemical reaction
• tumor cells
• medical knowledge
• medical research
• analysis of cytoplasmic
• Crystal structure
• bacteria
• hemoglobin
• medicine
• cell proliferation
• breast cancer
• gastric cancer
• hormone medicine
• biochemical studies
• environmental medicine