AMP-activated protein kinase activates transcription of the UCP3 and HKII genes in rat skeletal muscle

Stoppani, James, Hildebrandt, Audrey L., Sakamoto, Kei, Cameron-Smith, David, Goodyear, Laurie J. and Neufer, P. Darrell 2002, AMP-activated protein kinase activates transcription of the UCP3 and HKII genes in rat skeletal muscle, American journal of physiology, endocrinology and metabolism, vol. 283, pp. E1239-E1248.

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Title AMP-activated protein kinase activates transcription of the UCP3 and HKII genes in rat skeletal muscle
Author(s) Stoppani, James
Hildebrandt, Audrey L.
Sakamoto, Kei
Cameron-Smith, David
Goodyear, Laurie J.
Neufer, P. Darrell
Journal name American journal of physiology, endocrinology and metabolism
Volume number 283
Start page E1239
End page E1248
Publisher American Physiological Society
Place of publication [Bethesda, Md.]
Publication date 2002-09-11
ISSN 0193-1849
Keyword(s) 5-aminoimidazole-4-carboxamide ribonucleoside
single-leg arterial infusion
AMP kinase phosphorylation
Summary AMP-activated protein kinase (AMPK) has recently emerged as a key signaling protein in skeletal muscle, coordinating the activation of both glucose and fatty acid metabolism in response to increased cellular energy demand. To determine whether AMPK signaling may also regulate gene transcription in muscle, rats were given a single subcutaneous injection (1 mg/g) of the AMP analog 5-aminoimidazole-4-carboxamide-1-ß-D-ribonucleoside (AICAR). AICAR injection activated (P < 0.05) AMPK-α2 (~2.5-fold) and transcription of the uncoupling protein-3 (UCP3, ~4-fold) and hexokinase II (HKII, ~10-fold) genes in both red and white skeletal muscle. However, AICAR injection also elicited (P < 0.05) an acute drop (60%) in blood glucose and a sustained (2-h) increase in blood lactate, prompting concern regarding the specificity of AICAR on transcription. To maximize AMPK activation in muscle while minimizing potential systemic counterregulatory responses, a single-leg arterial infusion technique was employed in fully conscious rats. Relative to saline-infused controls, single-leg arterial infusion of AICAR (0.125, 0.5, and 2.5 µg · g-1 · min-1 for 60 min) induced a dose-dependent increase (2- to 4-fold, P < 0.05) in UCP3 and HKII transcription in both red and white skeletal muscle. Importantly, AICAR infusion activated transcription only in muscle from the infused leg and had no effect on blood glucose or lactate levels. These data provide evidence that AMPK signaling is linked to the transcriptional regulation of select metabolic genes in skeletal muscle.
Language eng
Field of Research 060405 Gene Expression (incl Microarray and other genome-wide approaches)
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2002, American Physiological Society
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