Non‑toxic sulfur enhances growth hormone signaling through the JAK2/STAT5b/IGF‑1 pathway in C2C12 cells

Abstract

Insulin-like growth factor-1 (IGF-1) regulates cell growth, glucose uptake and protein metabolism, and is required for growth hormone (GH) signaling-mediated insulin production and secretion. IGF1 expression is associated with STAT5, which binds to a region (TTcNNNGAA) of the gene. Although sulfur is used in various fields, the toxicity of this element is a significant disadvantage as it causes indigestion, vomiting, diarrhea, pain and migraine. Therefore, it is difficult to conduct in vitro experiments to directly determine the effects of dietary sulfur. Additionally, it is difficult to dissolve non-toxic sulfur (NTS). The present study aimed to identify the role of NTS in GH signaling as a Jak2/STAT5b/IGF-1 pathway regulator. MTT assay was used to identify an optimum NTS concentration for c2c12 mouse muscle cells. Western blotting, RT-PcR, chromatin immunoprecipitation, overexpression and small interfering RNA analyses were performed. NTS was dissolved in 1 mg/ml dMSO and could be used in vitro. Therefore, the present study determined whether NTS induced mouse muscle cell growth via GH signaling. NTS notably increased STAT5b binding to the Igf1 promoter. NTS also promoted GH signaling by upregulating GH receptor expression, similar to GH treatment. NTS enhanced GH signaling by regulating Jak2/STAT5b/IGF-1 signaling pathway factor expression in C2C12 mouse muscle cells. Thus, NTS may be used as a GH-enhancing growth stimulator.

Natural Sulfurs Inhibit LPS-Induced Inflammatory Responses through NF-κB Signaling in CCD-986Sk Skin Fibroblasts

“…NTS is a form of non-toxic mineral sulfur. Studies have shown the ability of NTS to enhance growth hormone signaling via the JAK2/STAT5b/IGF-1 axis and to produce anti-inflammatory effects against hyperglycemia in human monocytes [22,35]. MSM is another sulfur-containing natural compound with…”

“…NTS is a form of non-toxic mineral sulfur. Studies have shown the ability of NTS to enhance growth hormone signaling via the JAK2/STAT5b/IGF-1 axis and to produce anti-inflammatory effects against hyperglycemia in human monocytes [ 22 , 35 ]. MSM is another sulfur-containing natural compound with various anti-inflammatory activities [ 38 ] and exercise-induced stress in racing horse muscle cells via p53-mediated SDHA/HPRT1 expression [ 39 ].…”

“…Non-toxic sulfur (NTS) has been used in livestock feed to enhance immunity and meat quality, and studies have shown that oral administration of NTS in rats does not induce cell death [ 33 , 34 ]. NTS exhibits anti-inflammatory activity against human THP-1 cells [ 22 ] and enhances growth hormone signaling in mouse C2C12 cells [ 35 ].…”

Non-toxic sulfur inhibits LPS-induced inflammation by regulating TLR-4 and JAK2/STAT3 through IL-6 signaling

“…It has been reported that repeated oral administration of NTS in rats did not induce cell death ( 23 , 24 ). In addition, it has been demonstrated that NTS can enhance growth hormone signaling by regulating the JAK2/STAT5b/IGF-1 axis ( 25 ). The present study hypothesized that NTS exhibits anti-inflammatory activity against LPS-induced inflammation by regulating JAK2/STAT3/IL-6 signaling.…”

Sulfur Compounds Inhibit High Glucose-Induced Inflammation by Regulating NF-κB Signaling in Human Monocytes

“…Many countries, including the USA, use a non-toxic form of dietary sulfur or natural sulfur for the treatment of many diseases, including inflammatory diseases [31]. A recent study demonstrated that non-toxic sulfur (NTS) extracted and processed from mineral sulfur enhances growth hormone signaling in mouse muscle cells [32]. Methylsulfonylmethane (MSM) is also a natural organic sulfur-containing compound present in food and beverages [33].…”