The misbehaving attitude of Ca signaling pathways could be the probable reason in many muscular disorders such as myopathies, systemic disorders like hypoxia, sepsis, cachexia, sarcopenia, heart failure, and dystrophy. The present review throws light upon the calcium flux regulating signaling channels like ryanodine receptor complex (RyR1), SERCA (Sarco-endoplasmic Reticulum Calcium ATPase), DHPR (Dihydropyridine Receptor) or Cav1.1 and Na+/Ca exchange pump in detail and how remodelling of these channels contribute towards disturbed calcium homeostasis. Understanding these pathways will further provide an insight for establishing new therapeutic approaches for the prevention and treatment of muscle atrophy under stress conditions, targeting calcium ion channels and associated regulatory proteins.
While numerous maladies are associated with hypobaric hypoxia, muscle protein loss is an important under studied topic. Hence, the present study was designed to investigate the mechanism of muscle protein loss at HH. SD rats were divided into normoxic rats, while remaining rats were exposed to simulated hypoxia equivalent to 282-torr pressure (equal to an altitude of 7620 m, 8% oxygen), at 25 °C for 6, 12, and 24 h. Post-exposure rats were sacrificed and analysis was performed. Ergo, muscle loss-related changes were observed at 12 and 24 h post-HH exposure. An increased reactive oxygen species production and decreased thiol content was observed in HH-exposed rats. This disturbance caused substantial protein oxidative modification in the form of protein carbonyl content and advanced oxidation protein products. The analysis showed increase levels of bityrosine, oxidized tryptophan, lysine conjugate, lysine conjugate with MDA, protein hydroperoxide, and protein-MDA product. These changes were also in agreement with increase in lipid hydroperoxides and MDA content. HSP-70 and HSP-60 were upregulated significantly, and this finding is corroborated with increase in ER stress biomarker, GRP-78. Overloading of cells with misfolded proteins further activated degradative machinery. Consequently, pro-apoptotic signaling cascade, caspase-3, and C/EBP homologous protein were also activated in 24-h HH exposure. Release of tryptophan and tyrosine was also increased with 24-h HH exposure, indicated protein degradation. Elevation in resting intracellular calcium ion, [Ca]i, was also observed at 12- and 24-h HH exposure. The present study provides a detailed mechanistic representation of muscle protein loss during HH exposure.
In the present study, we aimed to elucidate the antioxidant property and anti-inflammatory activity of the aqueous extract of the Indian species of Ophiocordyceps sinensis (AECS), which demonstrates medicinal activity against numerous diseases. The chemical composition of AECS was quantified using a colorimeteric technique to determine the total phenolic and flavonoid contents. Antioxidant activity was determined by assays for 2,2'-azinobis(3-ethylbenzothiazoline-6-sulphonic acid)diammonium salt (ABTS); 2,2-diphenyl-1-picryl-hydrazyl (DPPH); and ferric reducing antioxidant power (FRAP). Adenosine nucleoside and nitrogenous bases (adenine and uracil) were also quantified by high-performance thin layer chromatography (HPTLC). Furthermore, the aqueous extract was also analyzed for anti-inflammatory activity in vitro using THP1 cells. THP1 cells were treated with and without lipopolysaccharide (LPS) and AECS (at 25 µg/mL, 50 µg/mL and 100 µg/mL, respectively) for 24 h. After 24 h, supernatants were harvested and kept at -80°C until the cytokine assays were performed. Furthermore, nitric oxide (NO) content was also estimated in treated and untreated murine peritoneal macrophages using Griess reagent. AECS significantly suppressed LPS-induced release of TNF-α and IL-1β in THP1 cells and significantly suppressed NO release in macrophage cells without exerting any toxic effect. These results indicate the anti-inflammatory activity of AECS. Additionally, this extract also has an antioxidant property, as high contents of phenols and flavonoids are present in the extract with considerable reducing power. The results of this study clearly demonstrate the potent antioxidant property and anti-inflammatory activity of AECS. Therefore, consumption of AECS may be clinically useful to protect against inflammatory diseases.
Hypobaric hypoxic stress leads to oxidative stress, inflammation, and disturbance in protein turnover rate. Aggregately, this imbalance in redox homeostasis is responsible for skeletal muscle protein loss and a decline in physical performance. Hence, an urgent medical need is required to ameliorate skeletal muscle protein loss. The present study investigated the efficacy of ursolic acid (UA), a pentacyclic triterpene acid to ameliorate hypobaric hypoxia (HH)induced muscle protein loss. UA is a naturally occurring pentacyclic triterpene acid present in several edible herbs and fruits such as apples. It contains skeletal muscle hypertrophy activity; still its potential against HH-induced muscle protein loss is unexplored. To address this issue, an in vivo study was planned to examine the beneficial effect of UA supplementation on HH-induced skeletal muscle loss. Male Sprague Dawley rats were exposed to HH with and without UA supplementation (20 mg/kg; oral) for 3 continuous days. The results described the beneficial role of UA as supplementation of UA with HH exposure attenuated reactive oxygen species production and oxidative protein damage, which indicate the potent antioxidant activity. Furthermore, UA supplementation enhanced Akt, pAkt, and p70S6kinase activity (Akt pathway) and lowered the pro-inflammatory cytokines in HH exposed rats. UA has potent antioxidant and anti-inflammatory activity, and it enhanced the protein content via upregulation of Akt pathway-related proteins against HH exposure. These three biological activities of UA make it a novel candidate for amelioration of HH-induced skeletal muscle damage and protein loss.
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