Chronic low-frequency stimulation upregulates uncoupling protein-3 in transforming rat fast-twitch skeletal muscle.
The purpose of this investigation was to examine the temporal changes in uncoupling protein (UCP)-3 expression, as well as related adaptive changes in mitochondrial density and fast-to-slow fiber type transitions during chronically enhanced contractile activity. We examined the effects of 1-42 days of chronic low-frequency electrical stimulation (CLFS), applied to rat tibialis anterior (TA) for 10 h/day, on the expression of UCP-3 and concomitant changes in myosin heavy chain (MHC) protein expression and increases in oxidative capacity. UCP-3 protein content increased from 1 to 12 days, reaching 1.5-fold over control (P < 0.0005); it remained elevated for up to 42 days. In contrast, UCP-3 mRNA decreased in response to CLFS, reaching a level that was threefold lower than control (P < 0.0007). The activities of the mitochondrial reference enzymes citrate synthase (EC 4.1.3.7) and 3-hydroxyacyl-CoA-dehydrogenase (EC 1.1.1.35), which are known to increase in proportion to mitochondrial density, progressively increased up to an average of 2.3-fold (P < 0.00001). These changes were accompanied by fast-to-slow fiber type transitions, characterized by a shift in the pattern of MHC expression (P <0.0002): MHCI and MHCIIa expression increased by 1.7- and 4-fold, whereas MHCIIb displayed a 2.4-fold reduction. We conclude that absolute increases in UCP-3 protein content in the early adaptive phase were associated with the genesis of mitochondria containing a normal complement of UCP-3. However, during exposure to long-term CLFS, mitochondria were generated with a lower complement of UCP-3 and coincided with the emergence of a growing population of oxidative type IIA fibers.
Putman
Charles T
CT
Exercise Biochemsitry Laboratory, Faculty of Physical Education and Recreation, University of Alberta, Edmonton, Alberta, Canada T6G 2H9. tputman@ualberta.ca
Dixon
Walter T
WT
Pearcey
Jean A
JA
Maclean
Ian M
IM
Jendral
Michelle J
MJ
Kiricsi
Mónika
M
Murdoch
Gordon K
GK
Pette
Dirk
D
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000235:genetics; D000199:Actins / Q000235:genetics; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D004558:Electric Stimulation; D005786:Gene Expression Regulation; D007700:Kinetics; D008297:Male; D026901:Membrane Transport Proteins; D008931:Mitochondria, Muscle / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D000071245:Mitochondrial Uncoupling Proteins; D018656:Muscle Fibers, Fast-Twitch / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000199:Actins; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D000071245:Mitochondrial Uncoupling Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C492125:Slc25a14 protein, rat; D015094:3-Hydroxyacyl CoA Dehydrogenases