Role of nitration in control of phosphorylase and glycogenolysis in mouse skeletal muscle
| Autor: | Sarah J. Blackwood, Baptiste Jude, Johanna T. Lanner, Abram Katz, Theresa Mader |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Fysiologi Contraction (grammar) Glycogenolysis Phosphorylases Physiology Endocrinology Diabetes and Metabolism phosphorylase Mice 03 medical and health sciences chemistry.chemical_compound Glycogen phosphorylase 0302 clinical medicine Peroxynitrous Acid Physiology (medical) Nitration Internal medicine medicine Animals skeletal muscle Muscle Skeletal Nitrates Glycogen contraction Skeletal muscle Hydrogen Peroxide Metabolism Mice Inbred C57BL antioxidants 030104 developmental biology medicine.anatomical_structure Endocrinology chemistry Nitrosative Stress glycogen 030217 neurology & neurosurgery Peroxynitrite Muscle Contraction |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 320:E691-E701 |
| ISSN: | 1522-1555 0193-1849 |
| Popis: | Phosphorylase is one of the most carefully studied proteins in history, but knowledge of its regulation during intense muscle contraction is incomplete. Tyrosine nitration of purified preparations of skeletal muscle phosphorylase results in inactivation of the enzyme and this is prevented by antioxidants. Whether an altered redox state affects phosphorylase activity and glycogenolysis in contracting muscle is not known. Here, we investigate the role of redox state in control of phosphorylase and glycogenolysis in isolated mouse fast-twitch (extensor digitorum longus, EDL) and slow-twitch (soleus) muscle preparations during repeated contractions. Exposure of crude muscle extracts to H2O2 had little effect on phosphorylase activity. However, exposure of extracts to peroxynitrite (ONOO-), a nitrating/oxidizing agent, resulted in complete inactivation of phosphorylase (half maximal inhibition at ~200 µM ONOO-), which was fully reversed by the presence of an ONOO-scavanger, dithiothreitol (DTT). Incubation of isolated muscles with ONOO- resulted in nitration of phosphorylase and marked inhibition of glycogenolysis during repeated contractions. ONOO- also resulted in large decreases in high-energy phosphates (ATP and phosphocreatine) in the rested state and following repeated contractions. These metabolic changes were associated with decreased force production during repeated contractions (to ~60% of control). In contrast, repeated contractions did not result in nitration of phosphorylase, nor did DTT or the general antioxidant N-acetylcysteine alter glycogenolysis during repeated contractions. These findings demonstrate that ONOO- inhibits phosphorylase and glycogenolysis in living muscle under extreme conditions. However, nitration does not play a significant role in control of phosphorylase and glycogenolysis during repeated contractions. |
| Databáze: | OpenAIRE |
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