A natural antioxidant pine bark extract, Oligopin®, regulates the stress chaperone HSPB1 in human skeletal muscle cells: a proteomics approach.

The gradual loss of muscle mass affecting all the elderly (sarcopenia) is most likely due to a decreased number and/or function of satellite cells. Accumulation of reactive oxygen species (ROS) has been clearly correlated to sarcopenia and could contribute to the impairment of satellite cell function. In this study, we analyzed the protective mechanism of action of a natural pine bark extract (Oligopin®) in human muscle satellite cells exposed to oxidative stress (H2O2). This polyphenol belongs to the flavonoid family and was able to abolish the H2 O2-induced apoptotic cell death. A large-scale proteomic strategy allowed us to identify several proteins that may function as early regulators of ROS-mediated events in muscle cells. Interestingly, we identified the stress chaperone heat shock protein beta-1, a main protector of muscle necrosis, as a target of Oligopin® and showed that this polyphenol was able to modulate its stress induced phosphorylation.

Investigation of peroxiredoxin IV as a calpain-regulated pathway in cancer.

Peroxiredoxin IV (Prx IV), a member of the peroxiredoxin family, has been shown to be involved in cell protection against radiation. Peroxiredoxins are also overexpressed and involved in the progression of several tumours. Calpains have been shown to be over-activated in alveolar rhabdomyosarcoma (ARMS). The present study focused on the possible cross-regulations between Prx IV and calpains in ARMS cells. Prx IV abundance was quantified by Western blot analysis in ARMS cells and compared with non-malignant LHCN-M2 cells. Its abundance is quantified in ARMS cells treated or untreated with calpain inhibitors moreover its mRNA expression is also quantified by real-time RT-PCR in these cells. The study showed that Prx IV is overexpressed by five times in ARMS cells when compared to non-malignant myoblasts. Moreover, the inhibition of calpains using chemical inhibitors led to a decrease in Prx IV abundance (64.32 ± 8.25 and 76.79 ± 4.60 for the precursor and secretable forms, respectively, with calpain inhibitor III treatment). It is the first time that a Prx IV calpain-dependent up-regulation is revealed. In summary, calpains may be implied in the tumour phenotype of ARMS cells especially through Prx IV regulation and may, thus, represent a potential therapeutic target to stop progression of ARMS tumour.