Alox15, also known as 15-lipoxygenase-1 or 12/15-lipoxygenase (12/15-LOX), is an enzyme that oxidizes polyunsaturated fatty acids, especially omega-6 and-3 fatty acids, to produce bioactive lipid metabolites. It is involved in oxidative and inflammatory responses, and plays a role in the formation of key lipid mediators like lipoxins and resolvins to terminate inflammation [2,3].

In a left anterior descending coronary artery ligation mouse model, myocardial-specific knockout of Alox15 alleviated myocardial ischemia-reperfusion (I/R) injury and restored cardiac function. 15-Hydroperoxyeicosatetraenoic acid (15-HpETE), an Alox15-derived metabolite, was identified as a trigger for cardiomyocyte ferroptosis during prolonged I/R injury [1]. In the context of asthma, silencing Alox15 in HDM/LPS-stimulated 16HBE cells decreased ferroptosis, suggesting its role in asthma-related ferroptosis [4]. In cervical cancer, macrophages-derived exosomes containing miRNA-660-5p attenuate Alox15 expression in cancer cells to suppress ferroptosis, and Alox15 expression is positively associated with good prognosis [5].

In conclusion, Alox15 is crucial in processes related to oxidative and inflammatory responses. Studies using gene knockout mouse models, such as in myocardial I/R injury, asthma, and cervical cancer, have revealed its role in ferroptosis regulation. Understanding Alox15 function provides insights into the pathogenesis of these diseases and may offer potential therapeutic targets.

References:

1. Cai, Wenbin, Liu, Le, Shi, Xuelian, Zhu, Yi, Zhang, Xu. 2023. Alox15/15-HpETE Aggravates Myocardial Ischemia-Reperfusion Injury by Promoting Cardiomyocyte Ferroptosis. In Circulation, 147, 1444-1460. doi:10.1161/CIRCULATIONAHA.122.060257. https://pubmed.ncbi.nlm.nih.gov/36987924/

2. Singh, Nikhlesh K, Rao, Gadiparthi N. 2018. Emerging role of 12/15-Lipoxygenase (ALOX15) in human pathologies. In Progress in lipid research, 73, 28-45. doi:10.1016/j.plipres.2018.11.001. https://pubmed.ncbi.nlm.nih.gov/30472260/

3. Tian, Rui, Zuo, Xiangsheng, Jaoude, Jonathan, Colby, Jennifer, Shureiqi, Imad. 2017. ALOX15 as a suppressor of inflammation and cancer: Lost in the link. In Prostaglandins & other lipid mediators, 132, 77-83. doi:10.1016/j.prostaglandins.2017.01.002. https://pubmed.ncbi.nlm.nih.gov/28089732/

4. Zhang, Weizhen, Huang, Fangfang, Ding, Xuexuan, Wang, Wenjian, Luo, Lianxiang. 2024. Identifying ALOX15-initiated lipid peroxidation increases susceptibility to ferroptosis in asthma epithelial cells. In Biochimica et biophysica acta. Molecular basis of disease, 1870, 167176. doi:10.1016/j.bbadis.2024.167176. https://pubmed.ncbi.nlm.nih.gov/38641013/

5. Luo, Yanlin, Chen, Yibing, Jin, Huan, Liu, Quentin, Zou, Zhengzhi. 2023. The suppression of cervical cancer ferroptosis by macrophages: The attenuation of ALOX15 in cancer cells by macrophages-derived exosomes. In Acta pharmaceutica Sinica. B, 13, 2645-2662. doi:10.1016/j.apsb.2023.03.025. https://pubmed.ncbi.nlm.nih.gov/37425043/