On the role of titin phosphorylation in the development of muscular atrophy

Salmov, N. N.; Gritsyna, Yu. V.; Уланова, А. Д.; Vikhlyantsev, I. M.; Podlubnaya, Z. A.

doi:10.1134/s0006350915040193

Cited by 4 publications

(1 citation statement)

References 28 publications

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“…Measurements of total titin phosphorylation in skeletal muscle demonstrated variable degrees of change under diverse stress conditions, including unloading during 30-day spaceflight [hyperphosphorylation in m. gastrocnemius of mice (87)], hibernation [constant phosphorylation in hibernating brown bears (80)], 6-mo chronic alcohol intake [hyperphosphorylation in m. gastrocnemius and m. soleus of rats (22)], or inherited forms of myopathy [hypophosphorylation in m. vastus lateralis of human patients vs. healthy subjects (88)]. Some of these changes were suggested to trigger increased proteolytic degradation of titin, which then contributes to the development of skeletal muscle atrophy (79). Various other studies proposed that altered phosphorylation state of I-band titin modifies titin-based spring force in skeletal myocytes (Fig.…”

Section: Modulation Of Titin Stiffness By Phosphorylationmentioning

confidence: 99%

Titin as a force-generating muscle protein under regulatory control

Freundt¹,

Linke²

2019

Journal of Applied Physiology

107

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Titin has long been recognized as a mechanical protein in muscle cells that has a main function as a molecular spring in the contractile units, the sarcomeres. Recent work suggests that the titin spring contributes to muscle contraction in a more active manner than previously thought. In this review, we highlight this property, specifically the ability of the immunoglobulin-like (Ig) domains of titin to undergo unfolding-refolding transitions when isolated titin molecules or skeletal myofibrils are held at physiological force levels. Folding of titin Ig domains under force is a hitherto unappreciated, putative source of work production in muscle cells, which could work in synergy with the actomyosin system to maximize the energy delivered by a stretched, actively contracting muscle. This review also focuses on the mechanisms shown to modulate titin-based viscoelastic forces in skeletal muscle cells, including chaperone binding, titin oxidation, phosphorylation, Ca2+ binding, and interaction with actin filaments. Along the way, we discuss which of these modulatory mechanisms might contribute to the phenomenon of residual force enhancement relevant for eccentric muscle contractions. Finally, a brief perspective is added on the potential for the alterations in titin-based force to dynamically alter mechano-chemical signaling pathways in the muscle cell. We conclude that titin from skeletal muscle is a determinant of both passive and active tension and a bona fide mechanosensor, whose stiffness is tuned by various independent mechanisms.

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Section: Modulation Of Titin Stiffness By Phosphorylationmentioning

confidence: 99%

Titin as a force-generating muscle protein under regulatory control

Freundt¹,

Linke²

2019

Journal of Applied Physiology

107

View full text Add to dashboard Cite

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Effect of titin phosphorylation on degradation of titin from skeletal muscles

Wang

Zhang

et al. 2023

Food Science and Human Wellness

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Chronic alcohol intoxication is not accompanied by an increase in calpain proteolytic activity in cardiac muscle of rats

Gritsyna

Salmov

Bobylev

et al. 2017

Biochemistry Moscow

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Enzymatic activity of Ca2+-dependent calpain proteases as well as the content and gene expression of μ-calpain (activated by micromolar calcium ion concentrations), calpastatin (inhibitor of calpains), and titin (substrate for calpains) were investigated in cardiac muscles of rats subjected to chronic alcoholization for 3 and 6 months. There was no increase in the "heart weight/body weight" parameter indicating development of heart hypertrophy in the alcoholized rats, while a decreasing trend was observed for this parameter in the rats after 6-month modeling of alcoholic cardiomyopathy, which indicated development of atrophic changes in the myocardium. Fluorometric measurements conducted using the Calpain Activity Assay Kit did not reveal any changes in total calpain activity in protein extracts of cardiac muscles of the rats alcoholized for 3 and 6 months. Western blot analysis did not show reliable changes in the contents of μ-calpain and calpastatin, and SDS-PAGE did not reveal any decrease in the titin content in the myocardium of rats after the chronic alcohol intoxication. Autolysis of μ-calpain was also not verified, which could indicate that proteolytic activity of this enzyme in myocardium of chronically alcoholized rats is not enhanced. Using Pro-Q Diamond staining, changes in phosphorylation level of titin were not detected in cardiac muscle of rats after chronic alcoholization during three and six months. A decrease in µ-calpain and calpastatin mRNA content (~1.3-fold, p ≤ 0.01 and ~1.9-fold, p ≤ 0.01, respectively) in the myocardium of rats alcoholized for 3 months and decrease in calpastatin mRNA (~1.4-fold, p ≤ 0.01) in animals alcoholized for 6 months was demonstrated using real-time PCR. These results indicate negative effect of chronic alcohol intoxication on expression of the abovementioned genes.

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On the role of titin phosphorylation in the development of muscular atrophy

Cited by 4 publications

References 28 publications

Titin as a force-generating muscle protein under regulatory control

Titin as a force-generating muscle protein under regulatory control

Effect of titin phosphorylation on degradation of titin from skeletal muscles

Chronic alcohol intoxication is not accompanied by an increase in calpain proteolytic activity in cardiac muscle of rats

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