Gstm4, a member of the glutathione S-transferases (GSTs) superfamily, is an enzyme that uses glutathione as a cofactor for antioxidant and detoxification processes [2,6]. GSTs play a role in protecting cells from oxidative stress and electrophilic compounds, which are involved in various cellular processes and disease-related pathways.

In a study on diet-induced obesity and dyslipidemia, hepatic deletion of Gstm4 in mice did not lead to changes in body weight, serum lipid profile, or liver fat content under chow or high-fat high-cholesterol diet feeding. However, it was found that the protein level of Npc1l1, a key protein for cholesterol uptake, was upregulated, suggesting a potential link between Gstm4 and lipid metabolic diseases in certain contexts [2]. In Ewing's sarcoma, reduction of GSTM4 levels caused a loss of oncogenic transformation and increased sensitivity to chemotherapeutic agents. High GSTM4 expression in tumors was associated with poor patient outcomes, indicating its role in cancer cell behavior and drug resistance [3,4]. In endometriosis, GSTM4 expression was significantly increased, and its suppression by NBDHEX inhibited cell growth, migration, and invasion, and affected oxidative stress-induced apoptosis [5].

In conclusion, Gstm4 is essential in antioxidant and detoxification functions. Studies using gene-knockout mouse models have revealed its potential involvement in lipid metabolism, cancer development, and endometriosis. These findings contribute to understanding the role of Gstm4 in disease processes and suggest its potential as a therapeutic target in conditions such as migraine, Ewing's sarcoma, and endometriosis [1,3,4,5].

References:

1. Sun, Xinyue, Chen, Bohong, Qi, Yi, Lei, Xiangyu, Luo, Guogang. 2024. Multi-omics Mendelian randomization integrating GWAS, eQTL and pQTL data revealed GSTM4 as a potential drug target for migraine. In The journal of headache and pain, 25, 117. doi:10.1186/s10194-024-01828-w. https://pubmed.ncbi.nlm.nih.gov/39039470/

2. Hu, Liwei, Yuan, Delong, Zhu, Qihan, Yang, Yunzhi, He, Anyuan. 2024. Evaluation of the role of hepatic Gstm4 in diet-induced obesity and dyslipidemia. In Biochemical and biophysical research communications, 737, 150920. doi:10.1016/j.bbrc.2024.150920. https://pubmed.ncbi.nlm.nih.gov/39481188/

3. Luo, W, Gangwal, K, Sankar, S, Thomas, D, Lessnick, S L. 2009. GSTM4 is a microsatellite-containing EWS/FLI target involved in Ewing's sarcoma oncogenesis and therapeutic resistance. In Oncogene, 28, 4126-32. doi:10.1038/onc.2009.262. https://pubmed.ncbi.nlm.nih.gov/19718047/

4. Zhuo, Rupeng, Kosak, Kenneth M, Sankar, Savita, Lessnick, Stephen L, Luo, Wen. 2014. Targeting Glutathione S-transferase M4 in Ewing sarcoma. In Frontiers in pediatrics, 2, 83. doi:10.3389/fped.2014.00083. https://pubmed.ncbi.nlm.nih.gov/25147782/

5. Liu, Wei, Cheng, Lei, Du, Yanbo, Ma, Jinlong, Yan, Lei. 2023. 6-(7-Nitro-2,1,3-benzoxadiazol-4-ylthio) Hexanol Inhibits Proliferation and Induces Apoptosis of Endometriosis by Regulating Glutathione S-Transferase Mu Class 4. In Reproductive sciences (Thousand Oaks, Calif.), 30, 2945-2961. doi:10.1007/s43032-023-01207-x. https://pubmed.ncbi.nlm.nih.gov/36928896/

6. Comstock, K E, Johnson, K J, Rifenbery, D, Henner, W D. . Isolation and analysis of the gene and cDNA for a human Mu class glutathione S-transferase, GSTM4. In The Journal of biological chemistry, 268, 16958-65. doi:. https://pubmed.ncbi.nlm.nih.gov/8349586/