The calcineurin antagonist RCAN1-4 is induced by exhaustive exercise in rat skeletal muscle

Abstract

The aim of this work was to study the regulation of the calcineurin antagonist regulator of calcineurin 1 (RCAN1) in rat skeletal muscles after exhaustive physical exercise, which is a physiological modulator of oxidative stress. Three skeletal muscles, namely extensor digitorum longus (EDL), gastrocnemius, and soleus, were investigated. Exhaustive exercise increased RCAN1-4 protein levels in EDL and gastrocnemius, but not in soleus. Protein oxidation as an index of oxidative stress was increased in EDL and gastrocnemius, but remained unchanged in soleus. However, lipid peroxidation was increased in all three muscles. CuZnSOD and catalase protein levels were increased at 3 h postexercise in soleus, whereas they remained unchanged in EDL and gastrocnemius. Calcineurin enzymatic activity declined in EDL and gastrocnemius but not in soleus, and its protein expression was decreased in all three muscles. The level of PGC1-α protein remained unchanged, whereas the protein expression of the transcription factor NFATc4 was decreased in all three muscles. Adiponectin expression was increased in all three muscles. RCAN1-4 expression in EDL and gastrocnemius muscles was augmented by the oxidative stress generated from exhaustive exercise. We propose that increased RCAN1-4 expression and the signal transduction pathways it regulates represent important components of the physiological adaptation to exercise-induced oxidative stress.

RCAN1.4 mediates high glucose-induced matrix production by stimulating mitochondrial fission in mesangial cells

“…We found that rat MCs have higher basal protein level of RCAN1.1 compared with RCAN1.4. HG induced the up-regulation of RCAN1.4 protein rather than RCAN1.1 protein, which is consistent with previous studies showed that RCAN1.1 is constitutively expressed in most issues, while RCAN1.4 transcription is induced de novo by several stimuli [32][33][34][35]. In addition, the mRNA level of RCAN1.4 rose in the early stage of HG stimulation and fell 12 h later, while the protein level of RCAN1.4 remained high at 36 h. The discrepancy between RCAN1.4 mRNA and protein levels suggested that there may be translational or post-translational regulation.…”

The neuronal and endocrine roles of RCAN1 in health and disease

“…RCAN1 is also overexpressed in the brains of individuals with Down syndrome, a disorder with an increased prevalence of AD . Neuronal expression of RCAN1 also increases with aging, and in response to traumatic stressors such as spinal cord injury and exhaustive exercise in muscle . The nutrient stress hyperglycaemia also induces RCAN1 expression in myotubes and pancreatic β‐cells .…”

“…19 Neuronal expression of RCAN1 also increases with aging, 20 and in response to traumatic stressors such as spinal cord injury 21 and exhaustive exercise in muscle. 22 The nutrient stress hyperglycaemia also induces RCAN1 expression in myotubes and pancreatic β-cells. 23,24 Such chronic increases in RCAN1 protein levels induce mitochondrial autophagy and a metabolic shift from oxidative phosphorylation to glycolysis in neuronal cells.…”

Dietary thymol supplementation promotes skeletal muscle fibre type switch in longissimus dorsi of finishing pigs

“…Oxidative muscle fibres mainly rely on sustained tonic contraction, and the intracellular Ca 2+ concentration is generally maintained at a relatively high level while glycolytic muscle fibres mainly undergo impulsive contraction with a Ca 2+ influx of transient and high intensity, which results in a higher concentration of Ca 2+ in slow muscle fibres than in fast muscle fibres (Zierath & Hawley, ). Recent studies have shown that the expressions of MyHC I and MyHC IIa are regulated by the Ca 2+ /calcineurin/NFAT pathway (Emrani et al, ; Ravel‐Chapuis, Bélanger, Côté, Michel, & Jasmin, ) pacifically, and increase of the intracellular Ca 2+ leads to calcineurin activation and NFAT dephosphorylation consequently. The dephosphorylated NFAT will translocate to the promoter of the gene involved in oxidative metabolism in the nucleus to promote the transformation of glycolytic muscle fibres to oxidative muscle fibres in skeletal muscle (Ehlers, Celona, & Black, ; Lomonosova, Turtikova, & Shenkman, ; Pfluger et al, ).…”

“…). Recent studies have shown that the expressions of MyHC I and MyHC IIa are regulated by the Ca 2+ /calcineurin/NFAT pathway(Emrani et al, 2015;Ravel-Chapuis, Bélanger, Côté, Michel, & Jasmin, 2017) pacifically, and increase of the intracellular Ca 2+ leads to calcineurin activation and NFAT dephosphorylation consequently. The dephosphorylated NFAT will…”