Effect of L-Arginine on Titin Expression in Rat Soleus Muscle After Hindlimb Unloading

Abstract

Nitric oxide (NO), produced by NO-synthases via L-arginine oxidation, is an essential trigger for signaling processes involved in structural and metabolic changes in muscle fibers. Recently, it was shown that L-arginine administration prevented the decrease in levels of the muscle cytoskeletal proteins, desmin and dystrophin, in rat soleus muscle after 14 days of hindlimb unloading. Therefore, in this study, we investigated the effect of L-arginine administration on the degree of atrophy changes in the rat soleus muscles under unloading conditions, and on the content, gene expression, and phosphorylation level of titin, the giant protein of striated muscles, able to form a third type of myofilaments—elastic filaments. A 7-day gravitational unloading [hindlimb suspension (HS) group] resulted in a decrease in the soleus weight:body weight ratio (by 31.8%, p < 0.05), indicating muscle atrophy development. The content of intact titin (T1) decreased (by 22.4%, p < 0.05) and the content of proteolytic fragments of titin (T2) increased (by 66.7%, p < 0.05) in the soleus muscle of HS rats, compared to control rats. The titin gene expression and phosphorylation level of titin between these two groups were not significantly different. L-Arginine administration under 7-day gravitational unloading decreased the degree of atrophy changes and also prevented the decrease in levels of T1 in the soleus muscle as compared to HS group. Furthermore, L-arginine administration under unloading resulted in increased titin mRNA level (by 76%, p < 0.05) and decreased phosphorylation level of T2 (by 28%, p < 0.05), compared to those in the HS group. These results suggest that administration of L-arginine, the NO precursor, under unloading decreased the degree of atrophy changes, increased gene expression of titin and prevented the decrease in levels of T1 in the rat soleus muscle. The results can be used to search for approaches to reduce the development of negative changes caused by gravitational unloading in the muscle.

Tail suspension is useful as a sarcopenia model in rats

“…A previous study has shown that the skeletal muscle atrophy starts during short-term unloading (at 2–4 days) [ 18 ] and that the SOL muscle atrophied to nearly half its original size in about 2 weeks [ 19 ]. Although a recent study indicated that 7 days of hind limb suspension was enough to reduce the SOL muscle weight in Wistar rats, the contraction and weight of EDL muscle were not measured [ 20 ]. The TS fixation method was simple because it involved the suspension of the tail only, whereas previous studies immobilized hind limbs by applying a cast [ 21 ].…”

Predominant synthesis of giant myofibrillar proteins in striated muscles of the long-tailed ground squirrel Urocitellus undulatus during interbout arousal

“…However, there are indirect data testifying that hyperphosphorylation of skeletal muscle titin enhances its sensitivity to cleavage by calpains (for references, see Ref. 55 ). Our data obtained in this work do not contradict this assumption.…”

Urinary Titin N-Fragment as a Biomarker of Muscle Atrophy, Intensive Care Unit-Acquired Weakness, and Possible Application for Post-Intensive Care Syndrome

“…Nutritional support prevents muscle breakdown in the chronic phase [ 116 ]. Regarding titin, Ulanova et al reported that L-arginine administration decreased the loss of titin in rat soleus muscle [ 117 ]. Since nutritional support team involvement can improve calorie and protein delivery [ 118 , 119 ], a multidisciplinary team intervention is expected to be important in PICS if urinary titin is elevated in patients.…”