Article ; Online: H 2 S- and Redox-State-Mediated PTP1B S-Sulfhydration in Insulin Signaling
International Journal of Molecular Sciences, Vol 24, Iss 2898, p
2023 Volume 2898
Abstract: Because hydrogen sulfide (H 2 S) is classified as a gaseous signaling molecule, protein S ... sulfhydration is known to be one of the mechanisms by which H 2 S signals are conducted. PTP1B, a negative ... However, the level of H 2 S, GSH, and GSSG was only significantly affected by insulin and metformin in HEK293T cells ...
Abstract | Because hydrogen sulfide (H 2 S) is classified as a gaseous signaling molecule, protein S-sulfhydration is known to be one of the mechanisms by which H 2 S signals are conducted. PTP1B, a negative regulator in insulin signaling, has been found to be S-sulfhydrated at Cys215-SH to form Cys215-SSH in response to endoplasmic reticulum (ER) stress. Therefore, we aimed to understand the change in PTP1B S-sulfhydration and cellular redox homeostasis in response to insulin stimulation. We demonstrated a feasible PEG-switch method to determine the levels of PTP1B S-sulfhydration. According to the results obtained from HEK293T and MDA-MB-231 cells, insulin induced a change in PTP1B S-sulfhydration that was similar to the change in Insulin receptor substrate 1 (IRS1) phosphorylation in both cell lines. However, insulin-induced PTP1B S-sulfhydration and IRS1 phosphorylation were only significantly affected by metformin in HEK293T cells. Insulin also induced an increase in reactive oxygen species (ROS) in both cell lines. However, the level of H 2 S, GSH, and GSSG was only significantly affected by insulin and metformin in HEK293T cells. HEK293T cells maintained high levels of H 2 S and cysteine, but low levels of GSSG and GSH in general compared to MDA-MB-231 cells. From these findings, we suggest that PTP1B activity is modulated by H 2 S and redox-regulated S-sulfhydration during insulin signaling. |
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Keywords | H 2 S ; S-sulfhydration ; PEG-switch ; PTP1B ; insulin ; glutathione ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999 |
Subject code | 571 |
Language | English |
Publishing date | 2023-02-01T00:00:00Z |
Publisher | MDPI AG |
Document type | Article ; Online |
Database | BASE - Bielefeld Academic Search Engine (life sciences selection) |
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