Alox8, also known as murine Alox15b, is a lipoxygenase that catalyzes the peroxidation of arachidonic acid at carbon-8. It oxygenates polyunsaturated fatty acids in S-chirality with specific reaction specificity. Alox8 is involved in the arachidonate metabolism pathway and plays a role in regulating cholesterol homeostasis in macrophages [1].

In mouse models, Alox8 deficiency has been associated with reduced atherosclerosis [1]. Chromosome 11B3 deletions or Alox8 loss in mice lead to up-regulation of the cyclooxygenase pathway, increased levels of prostaglandin E2, and contribute to B-cell malignancy [2]. Alox8-deficient mice also show age-dependent impaired recovery from influenza infection [3]. Moreover, intermittent fasting in mice after traumatic brain injury can partly abolish the increase of Alox8 induced by TBI, alleviating ferroptosis-related cellular damage and improving cognitive function [4].

In conclusion, Alox8 is essential in arachidonate metabolism and impacts various biological processes. Mouse models with Alox8 deficiency have revealed its role in diseases such as atherosclerosis, B-cell lymphoma, and influenza recovery, as well as in neuronal ferroptosis after traumatic brain injury. These findings contribute to our understanding of the underlying mechanisms of these diseases and may provide potential therapeutic targets.

References:

1. Palmer, Megan A, Benatzy, Yvonne, Brüne, Bernhard. 2024. Murine Alox8 versus the human ALOX15B ortholog: differences and similarities. In Pflugers Archiv : European journal of physiology, 476, 1817-1832. doi:10.1007/s00424-024-02961-w. https://pubmed.ncbi.nlm.nih.gov/38637408/

2. Qi, Lu, Pan, Xiangyu, Chen, Xuelan, Liu, Yu, Xu, Zhengmin. 2023. COX-2/PGE2 upregulation contributes to the chromosome 17p-deleted lymphoma. In Oncogenesis, 12, 5. doi:10.1038/s41389-023-00451-9. https://pubmed.ncbi.nlm.nih.gov/36750552/

3. Alfardan, Rana, Guo, Changxiong, Toth, Linda A, Nie, Daotai. 2019. Impaired Recovery from Influenza A/X-31(H3N2) Infection in Mice with 8-Lipoxygenase Deficiency. In Medical sciences (Basel, Switzerland), 7, . doi:10.3390/medsci7040060. https://pubmed.ncbi.nlm.nih.gov/31013822/

4. Yang, Qiuyun, Li, Manrui, Liu, Jinyuan, Chen, Xiameng, Liang, Weibo. 2023. Intermittent fasting ameliorates neuronal ferroptosis and cognitive impairment in mice after traumatic brain injury. In Nutrition (Burbank, Los Angeles County, Calif.), 109, 111992. doi:10.1016/j.nut.2023.111992. https://pubmed.ncbi.nlm.nih.gov/36871445/