UCP-3 expression in skeletal muscle: effects of exercise, hypoxia, and AMP-activated protein kinase.
Uncoupling protein 3 (UCP-3), a member of the mitochondrial transporter superfamily, is expressed primarily in skeletal muscle where it may play a role in altering metabolic function under conditions of fuel depletion caused, for example, by fasting and exercise. Here, we show that treadmill running by rats rapidly (30 min) induces skeletal muscle UCP-3 mRNA expression (sevenfold after 200 min), as do hypoxia and swimming in a comparably rapid and substantial fashion. The expression of the mitochondrial transporters, carnitine palmitoyltransferase 1 and the tricarboxylate carrier, is unaffected under these conditions. Hypoxia and exercise-mediated induction of UCP-3 mRNA result in a corresponding four- to sixfold increase in rat UCP-3 protein. We treated extensor digitorum longus (EDL) muscle with 5'-amino-4-imidazolecarboxamide ribonucleoside (AICAR), a compound that activates AMP-activated protein kinase (AMPK), an enzyme known to be stimulated during exercise and hypoxia. Incubation of rat EDL muscle in vitro for 30 min with 2 mM AICAR causes a threefold increase in UCP-3 mRNA and a 1.5-fold increase of UCP-3 protein compared with untreated muscle. These data are consistent with the notion that activation of AMPK, presumably as a result of fuel depletion, rapidly regulates UCP-3 gene expression.
Zhou
M
M
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118, USA.
Lin
B Z
BZ
Coughlin
S
S
Vallega
G
G
Pilch
P F
PF
D055372:AMP-Activated Protein Kinases; D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000096:biosynthesis*; D015342:DNA Probes / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D000860:Hypoxia / Q000201:enzymology / Q000378:metabolism*; D066298:In Vitro Techniques; D007473:Ion Channels; D008297:Male; D008931:Mitochondria, Muscle / Q000201:enzymology / Q000378:metabolism; D024101:Mitochondrial Proteins; D009097:Multienzyme Complexes / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D005082:Physical Exertion / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D012420:Running / Q000502:physiology; D013550:Swimming / Q000502:physiology; D000071247:Uncoupling Protein 3
D002352:Carrier Proteins; D015342:DNA Probes; D005230:Fatty Acids, Nonesterified; D007473:Ion Channels; D024101:Mitochondrial Proteins; D009097:Multienzyme Complexes; D009124:Muscle Proteins; D012333:RNA, Messenger; C000604394:Ucp3 protein, rat; D000071247:Uncoupling Protein 3; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases