Next Article in Journal
Gut Microbial Composition and Function Are Altered in Patients with Early Rheumatoid Arthritis
Previous Article in Journal
Genome-Wide Association between the 2q33.1 Locus and Intracranial Aneurysm Susceptibility: An Updated Meta-Analysis Including 18,019 Individuals
Previous Article in Special Issue
Muscle Involvement in a Large Cohort of Pediatric Patients with Genetic Diagnosis of Mitochondrial Disease
Article Menu
Issue 5 (May) cover image

Export Article

Open AccessArticle

Diverse Action of Selected Statins on Skeletal Muscle Cells—An Attempt to Explain the Protective Effect of Geranylgeraniol (GGOH) in Statin-Associated Myopathy (SAM)

1
Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences—SGGW, Warsaw, 02-787 Mazowieckie, Poland
2
Independent Laboratory of Genetics and Molecular Biology, The General Karol Kaczkowski Military Institute of Hygiene and Epidemiology, Warsaw, 01-163 Mazowieckie, Poland
3
Faculty of Biology and Environmental Protection, University of Łódź, 90-236 Łódzkie, Poland
4
Department of Biomedical and Clinical Sciences “Luigi Sacco”, Università degli Studi di Milano, 20157 Milano, Italy
5
Unit of Clinical Pharmacology, University Hospital “Luigi Sacco”-ASST Fatebenefratelli Sacco, 20157 Milano, Italy
*
Authors to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(5), 694; https://doi.org/10.3390/jcm8050694
Received: 6 March 2019 / Revised: 30 April 2019 / Accepted: 14 May 2019 / Published: 16 May 2019
(This article belongs to the Special Issue Advances in Metabolic Myopathies)
  |  
PDF [2725 KB, uploaded 17 May 2019]
  |  

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. View Full-Text
Keywords: skeletal muscle cell viability; statins; myotoxicity; geranylgeraniol; water-soluble cholesterol; statin-associated myopathy; mitochondrial bioenergetics skeletal muscle cell viability; statins; myotoxicity; geranylgeraniol; water-soluble cholesterol; statin-associated myopathy; mitochondrial bioenergetics
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Jaśkiewicz, A.; Pająk, B.; Łabieniec-Watała, M.; Palma, C.D.; Orzechowski, A. 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. 2019, 8, 694.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
J. Clin. Med. EISSN 2077-0383 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top