Diverse Action of Selected Statins on Skeletal Muscle Cells—An Attempt to Explain the Protective Effect of Geranylgeraniol (GGOH) in Statin-Associated Myopathy (SAM)
Articolo
Data di Pubblicazione:
2019
Citazione:
Diverse Action of Selected Statins on Skeletal Muscle Cells—An Attempt to Explain the Protective Effect of Geranylgeraniol (GGOH) in Statin-Associated Myopathy (SAM) / A. Jaskiewicz, B. Pajak, M. Labieniec-Watala, C. De Palma, A. Orzechowski. - In: JOURNAL OF CLINICAL MEDICINE. - ISSN 2077-0383. - 8:5(2019 May 16), pp. 694.1-694.22. [10.3390/jcm8050694]
Abstract:
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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
skeletal muscle cell viability; statins; myotoxicity; geranylgeraniol; water-soluble cholesterol; statin-associated myopathy; mitochondrial bioenergetics
Elenco autori:
A. Jaskiewicz, B. Pajak, M. Labieniec-Watala, C. DE PALMA, A. Orzechowski
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