H2S Protects Against Immobilization-Induced Muscle Atrophy via Reducing Oxidative Stress and Inflammation

Abstract

Chronic inflammation and oxidative stress are major triggers of the imbalance between protein synthesis and degradation during the pathogenesis of immobilization-induced muscle atrophy. This study aimed to elucidate the effects of hydrogen sulfide (H2S), a gas transmitter with potent anti-inflammatory and antioxidant properties, on immobilization-induced muscle atrophy. Mice were allocated to control and immobilization (IM) groups, which were treated with slow (GYY4137) or rapid (NaHS) H2S releasing donors for 14 days. The results showed that both GYY4137 and NaHS treatment reduced the IM-induced muscle loss, and increased muscle mass. The IM-induced expressions of Muscle RING finger 1 (MuRF1) and atrogin-1, two muscle-specific E3 ubiquitin ligases, were decreased by administration of GYY4137 or NaHS. Both GYY4137 and NaHS treatments alleviated the IM-induced muscle fibrosis, as evidenced by decreases in collagen deposition and levels of tissue fibrosis biomarkers. Moreover, administration of GYY4137 or NaHS alleviated the IM-induced infiltration of CD45 + leukocytes, meanwhile inhibited the expressions of the pro-inflammatory biomarkers in skeletal muscles. It was found that administration of either GYY4137 or NaHS significantly attenuated immobilization-induced oxidative stress as indicated by decreased H2O2 levels and 8-hydroxy-2′-deoxyguanosine (8-OHdG) immunoreactivity, as well as increased total antioxidant capacity (T-AOC), nuclear factor erythroid-2-related factor 2 (NRF2) and NRF2 downstream anti-oxidant targets levels in skeletal muscles. Collectively, the present study demonstrated that treatment with either slow or rapid H2S releasing donors protected mice against immobilization-induced muscle fibrosis and atrophy. The beneficial effects of H2S on immobilization-induced skeletal muscle atrophy might be due to both the anti-inflammatory and anti-oxidant properties of H2S.

Hypothalamic paraventricular nucleus hydrogen sulfide exerts antihypertensive effects in spontaneously hypertensive rats by attenuating oxidative stress via the Nrf2 pathway

“…H 2 S inhibits ROS-mediated CHOP apoptotic signaling in endoplasmic reticulum stress (Zhu et al, 2022). Administration of GYY4137 or NaHS improved overall antioxidant capacity and raised Nrf2 levels, which together dramatically reduced immobilization-induced oxidative stress (Xu et al, 2022). Additionally, the level of phosphorylated p47 phox was signi cantly reduced after NaHS infusion into RVLM, which would reduce the enzymatic activity of NADPH oxidase.…”

“…In an endotoxic shock model, H 2 S can block the release of TNF-α and IL-1β. Injections of NaHS or GYY4137, according to Xu et al, reduced the in ltration of CD45 + leukocytes brought on by immobilization while reducing the expression of proin ammatory biomarkers in skeletal muscle (Xu et al, 2022). Another study demonstrated that H 2 S inhibits the activation of the NLRP3 in ammasome, which slows the development of diabetesaccelerated atherosclerosis and protects endothelial cells (Zheng et al, 2019).…”

“…Studies (Li et al, 2022;Xu et al, 2022) have demonstrated that endogenous H 2 S has anti-in ammatory properties. H 2 S has been demonstrated to inhibit monocyte chemotaxis and decrease the synthesis of PICs like tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in a variety of in vitro and in vivo investigations.…”

Mechanistics of pH-Dependent Sulfmyoglobin Formation: Spin Control and His64 Proton Relay

“…Although the mechanism to generate the heme ferryl compound II and a thiyl radical, HS • , is diferent from the model proposed by Nicholls [57], the calculated energetic data indeed supported their hypothesis of the reaction between hem-eFe(IV)=O and the HS • to produce sulfheme. Furthermore, contrary to the classical peroxidative reaction of heme proteins with H 2 O 2 [60,61],the absence of the heme Cpd-I radical [Fe(IV)=O +• ] in sulfheme formation through reaction (1a) [53,59] supports the antioxidant role of hydrogen sulfde [18][19][20][21][22][23][24][25].…”

“…Reduced H 2 S levels are also related to Parkinson's, Alzheimer's, and atherosclerosis [14,15]. Furthermore, H 2 S has been correlated with chronic diseases [16,17], infammation [18,19], oxidative stress [20][21][22][23][24][25], oral diseases [26], glaucoma [27], subarachnoid hemorrhage [28], infertile men [29], arterial oxygen saturation [30], and skin diseases [31].…”