Beneficial effects of L-carnitine in myoblastic C2C12 cells. Interaction with zidovudine.
L-Carnitine is a key molecule in the transfer of fatty acid across mitochondrial membranes. Bioavailable L-carnitine is either provided by an endogeneous biosynthesis or after intestinal absorption of dietary items containing L-carnitine. After intestinal absorption or hepatic biosynthesis, L-carnitine is transferred to organs whose metabolism is dependent upon fatty acid oxidation, such as skeletal muscle. To cross the muscle plasma membrane, there are several transporters involved. Among those transporters, OCTN2 is actually the only one to have been clearly characterized. Zidovudine is a commonly used inhibitor of human immunodeficiency virus (HIV) replication. Zidovudine has many side effects, including induction of myopathy characterized by a metabolic mitochondria dysfunction and a diminution of the muscle L-carnitine content. In this study, we described the characteristics of L-carnitine transport in C2C12 cells. We also demonstrated that zidovudine inhibited the L-carnitine transporter. This inhibition led to a significant reduction of the muscle cell growth. In C2C12 cells, the supplementation of L-carnitine prevented the effects of zidovudine and restored the normal cell growth.
Georges
Béatrice
B
UPRES Lipides et Nutrition, Faculté Gabriel, Université de Bourgogne, 6 boulevard Gabriel, 21000, Dijon, France.
Galland
Stéphane
S
Rigault
Caroline
C
Le Borgne
Françoise
F
Demarquoy
Jean
J
D000818:Animals; D000963:Antimetabolites / Q000009:adverse effects / Q000494:pharmacology*; D001692:Biological Transport; D002331:Carnitine / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D004347:Drug Interactions; D007700:Kinetics; D051379:Mice; D032446:Myoblasts / Q000187:drug effects*; D013379:Substrate Specificity; D015215:Zidovudine / Q000009:adverse effects / Q000494:pharmacology*
D000963:Antimetabolites; D015215:Zidovudine; D002331:Carnitine