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

Kang,Dong  Young; Sp,Nipin; Jo,Eun  Seong; Kim,Hyoung  Do; Kim,Il  Ho; Bae,Se  Won; Jang,Kyoung‑Jin; Yang,Young  Mok

doi:10.3892/ijmm.2019.4451

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

Authors:
- Dong Young Kang
- Nipin Sp
- Eun Seong Jo
- Hyoung Do Kim
- Il Ho Kim
- Se Won Bae
- Kyoung‑Jin Jang
- Young Mok Yang
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Affiliations: Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Konkuk University, Chungju, North Chungcheong 27478, Republic of Korea, Nara Bio Co., Ltd., Jeonju, North Jeolla 54852, Republic of Korea, Green Chemistry and Materials Group, Korea Institute of Industrial Technology, Cheonan, South Chungcheong 31056, Republic of Korea
Published online on: December 31, 2019 https://doi.org/10.3892/ijmm.2019.4451
Pages: 931-938

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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.

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