l-arginine ingestion inhibits eccentric contraction-induced proteolysis and force deficit via S-nitrosylation of calpain Academic Article uri icon

abstract

  • It has been shown that calpains are involved in the proteolysis of muscle proteins that occurs with eccentric contraction (ECC) and that exogenously applied nitric oxide decreases the calpain-mediated proteolysis. The aim of this study was to examine the effects of ingestion of l-arginine (ARG), a nitric oxide precursor, on ECC-related calpain activation. In the first and second experiments, male Wistar rats were given ARG in water for 7 days starting from 3 days before the ECC protocol (average ingestion, ~600 mg kg-body wt-1  day-1 ). Tibialis anterior muscles underwent 200 repeated ECCs and, subsequently, were excised 3 days later. Whole muscle analyses (the first experiment) revealed that ARG attenuated ECC-induced force deficit and autolysis of calpain-1, and increased the amounts of S-nitrosylated calpain-1. Regarding ryanodine receptor (RyR) and dihydropyridine receptor (DHPR), ECC-induced proteolysis was completely inhibited by ARG, whereas the inhibition was partial for junctophilin-1 (JP1). Skinned fiber analyses (the second experiment) showed that ARG also inhibited ECC-elicited reductions in the ratio of depolarization-induced to maximum Ca2+ -activated force. In the third experiment, homogenates of rested muscles were treated with S-nitrosylating agent, S-nitrosoglutathione (GSNO), and/or high Ca2+ concentration ([Ca2+ ]). Treatment with high [Ca2+ ] and without GSNO produced proteolysis of RyR, DHPR, and JP1. On the other hand, treatment with high [Ca2+ ] and GSNO caused complete inhibition of RyR and DHPR proteolysis and partial inhibition of JP1 proteolysis. These results indicate that ARG ingestion can attenuate ECC-induced proteolysis of Ca2+ regulatory proteins and force deficit by decreasing calpain activation via S-nitrosylation.

authors

  • Kanzaki, K
  • Watanabe, Daiki
  • Aibara, C
  • Kawakami, Y
  • Yamada, T
  • Takahashi, Y
  • Wada, M

publication date

  • 2018