Antioxidant mito-TEMPO prevents the increase in tropomyosin oxidation and mitochondrial calcium accumulation under 7-day rat hindlimb suspension

Antioxidant mito-TEMPO prevents the increase in tropomyosin oxidation and mitochondrial calcium accumulation under 7-day rat hindlimb suspension Full article

Journal

Free Radical Biology and Medicine
ISSN: 1873-4596 , E-ISSN: 0891-5849

Output data

Year: 2024, Volume: 224, Pages: 822-830 Pages count : 9 DOI: 10.1016/j.freeradbiomed.2024.10.285

Authors

Sidorenko D.A. ¹ , Galkin G.V. ¹ , Bokov R.O. ¹ , Tyrina E.A. ¹ , Vilchinskaya N.A. ¹ , Lvova I.D. ¹ , Tyganov S.A. ¹ , Shenkman B.S. ¹ , Sharlo K.A. ¹

Affiliations

1	Institute of Biomedical Problems, RAS, Moscow, Russia

After the first day of muscle disuse (unloading) mitochondria-derived ROS accumulate in the postural-tonic soleus muscle. It is known that excess of ROS can lead to the accumulation of intramitochondrial calcium and overload of mitochondria with calcium, can negatively affect mitochondrial function and fatigue resistance of soleus muscle. We assumed that the use of mitochondrial ROS scavenger mito-TEMPO will be able to prevent the unloading-induced disruption of mitochondrial functions and will help maintain soleus muscle fatigue resistance. To test this hypothesis, male rats were divided into 3 groups (n=16 in each): vivarium control with placebo (C), 7-day hindlimb suspension with placebo (7HS) and 7-day hindlimb suspension with intraperitoneal administration of the mimetic superoxide dismutase mito-TEMPO at a dose of 1 mg/kg (7HSM). In the 7HS group, increased fatigue of the soleus muscle was found in the ex vivo test, accompanied with increased activity of ETC complex I and “leak” respiration, as well as a twofold increased content of oxidized tropomyosin (a marker of ROS level in tissues) and increase in intramitochondrial calcium compared to C. In 7HSM, the activity of ETC complex I and “leak” respiration had no significant differences from the control group, and the increase in intramitochondrial calcium and the content of oxidized tropomyosin was partially prevented, however, muscle fatigue was also significantly higher than in the control group. Thus, mitochondrial ROS under 7-day muscle unloading contribute to the accumulation of intramitochondrial calcium and oxidation of tropomyosin, but do not have a significant effect on soleus muscle function.

Sidorenko D.A. , Galkin G.V. , Bokov R.O. , Tyrina E.A. , Vilchinskaya N.A. , Lvova I.D. , Tyganov S.A. , Shenkman B.S. , Sharlo K.A.
Antioxidant mito-TEMPO prevents the increase in tropomyosin oxidation and mitochondrial calcium accumulation under 7-day rat hindlimb suspension
Free Radical Biology and Medicine. 2024. V.224. P.822-830. DOI: 10.1016/j.freeradbiomed.2024.10.285 WOS Scopus РИНЦ PMID OpenAlex

Web of science:	WOS:001337135300001
Scopus:	2-s2.0-85206253162
Elibrary:	75040997
PMID:	39406275
OpenAlex:	W4403374750

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