Protective effect of myokine IL-15 against H2O2-mediated oxidative stress in skeletal muscle cells

Abstract

The production of reactive oxygen species (ROS) during oxidative stress may cause cellular injury. Interleukin-15 (IL-15) is one of the skeletal muscle secreted myokines, and there is no information that reported its anti-oxidative capability in skeletal muscle. The aim of this study therefore is to investigate the protective effects of myokine IL-15 against H2O2-mediated oxidative stress in C2C12 myoblasts. The results showed that IL-15 pre-incubation reduced the intracellular creatine kinase and lactate dehydrogenase activities, decreased the ROS overload, and protect the mitochondrial network via up-regulated mRNA expression levels of IL-15 and uncoupling protein 3. It also down-regulated the levels of IL-6 and p21 of the myoblasts compared to the cells treated only with H2O2. Meanwhile, apurinic/aprimidinic endonuclease 1 expression and the Akt signaling pathway were stimulated. These effects could contribute to the resumption of cell viability and act as protective mechanism. In conclusion, myokine IL-15 could be a novel endogenous regulator to control intracellular ROS production and attenuate oxidative stress in skeletal muscle cells.

Protective Effect of Edaravone Against Oxidative Stress in C2C12 Myoblast and Impairment of Skeletal Muscle Regeneration Exposed to Ischemic Injury in Ob/ob Mice

“…Oxidative stress was induced by exposure to 250 µM H 2 O 2 for 4 h, which is one of the most widely used ROS to induce oxidative stress in cellular models (Li et al, 2014). Cells were also pretreated with or without 100 µM edaravone for 1 h. Edaravone was purchased from MedChemExpress LLC (South Brunswick Township, NJ, United States).…”

“…H 2 O 2 has been widely used for induction of the oxidative stress in in vitro studies, because previous studies showed that H 2 O 2 was sufficient and essential to induce oxidative stress on C2C12 mice skeletal myoblasts (Scherz-Shouval and Elazar, 2007;Li et al, 2014). As result, various antioxidants, including adiponectin and interleukin-15, were shown to have protective effects against H 2 O 2 -mediated oxidative stress in C2C12 mice skeletal myoblasts (Li et al, 2014;Ren et al, 2017). Clinical use of antioxidants has been expected to improve atrophy of the skeletal muscles due to oxidative stress, although clinically effective treatment has not been established.…”

Myokines in skeletal muscle physiology and metabolism: Recent advances and future perspectives

“…72,73 Acute IL-15 treatment of L6 myotubes mimicking circulating (1-10 pg/ml) and muscle interstitial (100 pg/ml-20ng/ml) IL-15 expression levels, enhances muscle glucose uptake and mitochondrial oxidative functions in association with activation of the AMPK pathway, a nutrient and exercise related pathway. 75,76 While the acute role of IL-15 seems beneficial, further investigations on the effects of IL-15 should be performed to understand if sustained elevation of IL-15 levels results in adverse effects, such as generating additional systemic inflammation. 74 It was also shown that IL-15 exerts protective effects against H 2 O 2 -mediated oxidative stress and enhances mitochondrial activity through a PPARδ-dependent mechanism in skeletal muscle cells.…”

“…74 It was also shown that IL-15 exerts protective effects against H 2 O 2 -mediated oxidative stress and enhances mitochondrial activity through a PPARδ-dependent mechanism in skeletal muscle cells. 75,76 While the acute role of IL-15 seems beneficial, further investigations on the effects of IL-15 should be performed to understand if sustained elevation of IL-15 levels results in adverse effects, such as generating additional systemic inflammation. A similar U-shaped profile of activity has been demonstrated with IL-6; IL-6 expression is increased within an acute timeframe after exercise which is beneficial, while chronic elevations of IL-6 are most likely detrimental.…”

Ex-Vivo Model for Muscle Exposure to Tumor Cell Conditioned Media

“…With regards to measuring ROS induced carbonylation using IL-15TG, overexpressing IL-15 mice it is important to note that IL-15 has been previously investigated as a potential protective mechanism against ROS activity. Li et al [66] found that pre-incubation with IL-15 reduced the activities of intracellular creatine kinase and lactate dehydrogenase, enzymes involved in various metabolic pathways in C2C12 myoblasts exposed to H 2 O 2 mediated oxidative stress. We can build on the work done by Li et al [66] using our model as we can potentially test ROS activity by exposing the muscle as a functional unit to H 2 O 2 mediated oxidative stress.…”