Glo1-KO Mouse

Glo1, also known as glyoxalase I, is a cytosolic protein expressed in all mammalian cells. Its primary function is the detoxification of methylglyoxal (MG), a potent precursor of advanced glycation end-products (AGEs), which is involved in the cellular glycolysis pathway. This detoxification process is crucial for maintaining normal cellular function and redox homeostasis [3,6].

Research has shown that modulation of Glo1 activity can regulate anxiety-like behavior and seizure-susceptibility in mice, likely through the regulation of MG, as MG acts as a competitive partial agonist at GABA(A) receptors. This suggests Glo1 as a novel target for neuropsychiatric and anti-epileptic drug development [1]. In hepatocellular carcinoma (HCC), Glo1 is overexpressed, activates the cell cycle pathway, and promotes cell proliferation and migration, making it a potential therapeutic target [2]. In glioma, high Glo1 expression is correlated with poor prognosis, and its overexpression in glioma cell lines enhances tumor cell proliferation, migration, and invasion [4]. Glo1 also contributes to the drug resistance of Escherichia coli by inducing PER-type of extended-spectrum β-lactamases [5]. In human skeletal muscle, loss of NAMPT and SIRT2 attenuates Glo1 expression and activity, while SIRT1 has no such effect [6]. In melanoma, genomic Glo1 deletion modulates TXNIP expression, glucose metabolism, and redox homeostasis, accelerating tumor growth [7]. In bladder cancer, miR-205-3p suppresses cancer progression via Glo1-mediated P38/ERK activation [8]. In HCC, Glo1 genetic amplification is associated with cell proliferation and survival, and interfering with Glo1 expression can inhibit tumor growth [9]. In a Chinese population, Glo1 SNPs are associated with gestational diabetes mellitus susceptibility [10].

In conclusion, Glo1 plays essential roles in multiple biological processes and disease conditions. Through various in vivo and in vitro functional studies, including gene knockout-related research, it has been revealed as a potential therapeutic target in many diseases, such as neuropsychiatric disorders, different types of cancers, bacterial drug-resistance, and gestational diabetes mellitus. Understanding Glo1's functions provides new insights into disease mechanisms and potential treatment strategies.

References:

1. McMurray, Katherine M J, Distler, Margaret G, Sidhu, Preetpal S, Palmer, Abraham A, Plant, Leigh D. . Glo1 inhibitors for neuropsychiatric and anti-epileptic drug development. In Biochemical Society transactions, 42, 461-7. doi:10.1042/BST20140027. https://pubmed.ncbi.nlm.nih.gov/24646261/

2. Zhang, Yao, Tang, Xiaolong, Liu, Lin, Yao, Lei, Du, Fukuan. 2024. GLO1 regulates hepatocellular carcinoma proliferation and migration through the cell cycle pathway. In BMC cancer, 24, 1297. doi:10.1186/s12885-024-12927-x. https://pubmed.ncbi.nlm.nih.gov/39434012/

3. Wortmann, Markus, Peters, Andreas S, Hakimi, Maani, Böckler, Dittmar, Dihlmann, Susanne. . Glyoxalase I (Glo1) and its metabolites in vascular disease. In Biochemical Society transactions, 42, 528-33. doi:10.1042/BST20140003. https://pubmed.ncbi.nlm.nih.gov/24646273/

4. Tian, Xiaomin, Wang, Yu, Ding, Xue, Cheng, Wei. 2019. High expression of GLO1 indicates unfavorable clinical outcomes in glioma patients. In Journal of neurosurgical sciences, 66, 228-233. doi:10.23736/S0390-5616.19.04805-7. https://pubmed.ncbi.nlm.nih.gov/31738028/

5. Ma, He, Lai, Bingjie, Zan, Chunfang, Zhu, Xinran, Wang, Ke. 2022. GLO1 Contributes to the Drug Resistance of Escherichia coli Through Inducing PER Type of Extended-Spectrum β-Lactamases. In Infection and drug resistance, 15, 1573-1586. doi:10.2147/IDR.S358578. https://pubmed.ncbi.nlm.nih.gov/35414749/

6. Miranda, Edwin R, Varshney, Pallavi, Mazo, Corey E, Ludlow, Andrew T, Haus, Jacob M. 2024. Loss of NAMPT and SIRT2 but not SIRT1 attenuate GLO1 expression and activity in human skeletal muscle. In Redox biology, 75, 103300. doi:10.1016/j.redox.2024.103300. https://pubmed.ncbi.nlm.nih.gov/39142179/

7. Jandova, Jana, Wondrak, Georg T. 2020. Genomic GLO1 deletion modulates TXNIP expression, glucose metabolism, and redox homeostasis while accelerating human A375 malignant melanoma tumor growth. In Redox biology, 39, 101838. doi:10.1016/j.redox.2020.101838. https://pubmed.ncbi.nlm.nih.gov/33360689/

8. Zhenhai, Zou, Qi, Cheng, Shuchao, Zhang, Beibei, Liu, Yuanyuan, Guo. 2023. MiR-205-3p suppresses bladder cancer progression via GLO1 mediated P38/ERK activation. In BMC cancer, 23, 956. doi:10.1186/s12885-023-11175-9. https://pubmed.ncbi.nlm.nih.gov/37814205/

9. Zhang, Shirong, Liang, Xiaodong, Zheng, Xiaoliang, Wang, Bing, Ma, Shenglin. 2014. Glo1 genetic amplification as a potential therapeutic target in hepatocellular carcinoma. In International journal of clinical and experimental pathology, 7, 2079-90. doi:. https://pubmed.ncbi.nlm.nih.gov/24966916/

10. Zeng, Qiaoli, Yang, Taili, Wei, Wenfeng, Huang, Jinzhi, Guo, Runmin. 2023. Association between GLO1 variants and gestational diabetes mellitus susceptibility in a Chinese population: a preliminary study. In Frontiers in endocrinology, 14, 1235581. doi:10.3389/fendo.2023.1235581. https://pubmed.ncbi.nlm.nih.gov/38027126/