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Jaskiewicz 2019 J Clin Med
Additional label 2019-05  + , MitoEAGLEPublication  +
Coupling states ROUTINE  + , OXPHOS  + , ET  + , LEAK  +
Diseases Myopathy  +
Has abstract The present study is centered on molecular
The present study is centered on molecular mechanisms of the cytoprotective effect of geranylgeraniol (GGOH) in skeletal muscle harmed by statin-associated myopathy (SAM). GGOH via autophagy induction was purportedly assumed to prevent skeletal muscle viability impaired by statins, atorvastatin (ATR) or simvastatin (SIM). The C2C12 cell line was used as the ''in vitro'' model of muscle cells at different stages of muscle formation, and the effect of ATR or SIM on the cell viability, protein expression and mitochondrial respiration were tested. Autophagy seems to be important for the differentiation of muscle cells; however, it did not participate in the observed GGOH cytoprotective effects. We showed that ATR- and SIM-dependent loss in cell viability was reversed by GGOH co-treatment, although GGOH did not reverse the ATR-induced drop in the cytochrome c oxidase protein expression level. It has been unambiguously revealed that the mitochondria of C2C12 cells are not sensitive to SIM, although ATR effectively inhibits mitochondrial respiration. GGOH restored proper mitochondria functioning. Apoptosis might, to some extent, explain the lower viability of statin-treated myotubes as the pan-caspase inhibitor, N-Benzyloxycarbonyl-Val-Ala-Asp(O-Me) fluoromethyl ketone (Z-VAD-FMK), partly reversed ATR- or SIM-induced cytotoxic effects; however, it does not do so in conjunction with caspase-3. It appears that the calpain inhibitor, N-Acetyl-L-leucyl-L-leucyl-L-norleucinal (ALLM), restored the viability that was reduced by ATR and SIM (''p'' < 0.001). GGOH prevents SAM, in part, as a consequence of a caspase-3 independent pathway, probably by calpain system inactivation.
, probably by calpain system inactivation.  +
Has editor [[Plangger M]]  +
Has info [ Open Access]  +
Has publicationkeywords Skeletal muscle cell viability  + , Statins  + , Myotoxicity  + , Geranylgeraniol  + , Water-soluble cholesterol  + , Statin-associated myopathy  + , Mitochondrial bioenergetics  + , C2C12 mouse myoblast cells  +
Has title Jaśkiewicz A, Pająk B, Łabieniec-Watała M,
Jaśkiewicz A, Pająk B, Łabieniec-Watała M, De Palma C, Orzechowski A (2019) Diverse action of selected statins on skeletal muscle cells - An attempt to explain the protective effect of geranylgeraniol (GGOH) in statin-associated myopathy (SAM). J Clin Med 8:694.
sociated myopathy (SAM). J Clin Med 8:694.  +
Instrument and method Oxygraph-2k  +
Mammal and model Mouse  +
MiP area Respiration  + , Pharmacology;toxicology  +
Pathways N  + , S  + , NS  + , ROX  +
Preparation Permeabilized cells  + , Intact cells  +
Tissue and cell Skeletal muscle  + , Other cell lines  +
Was published by MiPNetLab PL Lodz Watala C + , IT Milan Clementi E +
Was published in journal J Clin Med +
Was published in year 2019  +
Was written by Jaskiewicz A + , Pajak B + , Labieniec-Watala Magdalena + , De Palma C + , Orzechowski A +
Categories Publications
Modification date
"Modification date" is a predefined property that corresponds to the date of the last modification of a subject and is provided by Semantic MediaWiki.
10:28:07, 21 June 2019  +
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