Impairment of Electron Transfer Chain Induced by Acute Carnosine Administration in Skeletal Muscle of Young Rats

Abstract

Serum carnosinase deficiency is an inherited disorder that leads to an accumulation of carnosine in the brain tissue, cerebrospinal fluid, skeletal muscle, and other tissues of affected patients. Considering that high levels of carnosine are associated with neurological dysfunction and that the pathophysiological mechanisms involved in serum carnosinase deficiency remain poorly understood, we investigated the in vivo effects of carnosine on bioenergetics parameters, namely, respiratory chain complexes (I–III, II, and II-III), malate dehydrogenase, succinate dehydrogenase, and creatine kinase activities and the expression of mitochondrial-specific transcription factors (NRF-1, PGC-1α, and TFAM) in skeletal muscle of young Wistar rats. We observed a significant decrease of complexes I–III and II activities in animals receiving carnosine acutely, as compared to control group. However, no significant alterations in respiratory chain complexes, citric acid cycle enzymes, and creatine kinase activities were found between rats receiving carnosine chronically and control group animals. As compared to control group, mRNA levels of NRF-1, PGC-1α, and TFAM were unchanged. The present findings indicate that electron transfer through the respiratory chain is impaired in skeletal muscle of rats receiving carnosine acutely. In case these findings are confirmed by further studies and ATP depletion is also observed, impairment of bioenergetics could be considered a putative mechanism responsible for the muscle damage observed in serum carnosinase-deficient patients.

TFAM Enhances Fat Oxidation and Attenuates High-Fat Diet–Induced Insulin Resistance in Skeletal Muscle

“…These data also suggest that TFAM increased the aspartate-malate shuttle to increase NAD + import into the mitochondrial matrix. Carnosine, an inhibitor of electron transport chain (ETC) in animals (21), was also lower in Tg mice compared with Wt mice in both the chow and HFD groups (Fig. 2V).…”

Carnosine Inhibits the Proliferation of Human Cervical Gland Carcinoma Cells Through Inhibiting Both Mitochondrial Bioenergetics and Glycolysis Pathways and Retarding Cell Cycle Progression

“…A literature report showed that rats receiving carnosine acutely presented reduced activity of complexes I-III and II, as well as a trend of decrease in complexes II and III activities in skeletal muscle. 31 However, in cerebral cortex tissue of rats, acute carnosine treatment enhanced the activities of complexes I-III and II-III. 30 It has been shown that in the yeast Saccharomyces cerevisiae , carnosine produced contrasting effects on growth and viability, which suggested to be related to the organism’s energy metabolism.…”

Carnosine and Related Peptides: Therapeutic Potential in Age-Related Disorders

“…Consequently, carnosine levels in the human skeletal muscle [113], as well as the homocarnosine concentration in human CSF [114] significantly decrease with age. A recent paper published by Macarini and co-workers [115] corroborates such proposition. It was showed a significant decrease in the mitochondrial respiratory chain complexes I-III and II activities in skeletal muscle of young rats (30 days old) receiving carnosine (100 mg/kg body weight) acutely, as compared to animals receiving vehicle.…”