Cyp2j9-KO Mouse

Cyp2j9, a member of the cytochrome P450 CYP2J subfamily, is a mouse arachidonic acid omega-1 hydroxylase [2]. It metabolizes arachidonic acid to 19-hydroxyeicosatetraenoic acid (19-HETE) [2]. Involved in the arachidonic acid metabolism pathway, its products may play important functional roles in the body, especially in the brain where it is highly expressed [2]. Genetic models can be valuable to further explore its functions.

In lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice, the mRNA expression of Cyp2j9 decreased, along with Cyp2j6 and Cyp2j5. These genes metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs) [1]. The dysregulation of CYPs/COX-2 metabolism of arachidonic acid, including the change in Cyp2j9 expression, contributed to the uncontrolled inflammatory response in ALI [1]. In C57BL/6 mice, arsenic trioxide (ATO) induced Cyp2j9, which led to an increase in certain hydroxyeicosatetraenoic acids (HETEs) and might be related to ATO-induced hepatotoxicity [3]. In murine atrial HL-1 cells, Cyp2j9 was expressed at a similar level to that in mouse hearts, and 3-methylcholanthrene induced its mRNA level [4]. The CYP2J hemoproteins, including Cyp2j9, were detected in the mouse ductus arteriosus by immunofluorescence microscopy [5].

In conclusion, Cyp2j9 is crucial in arachidonic acid metabolism, especially in the brain. Its dysregulation in models like LPS-induced ALI and ATO-treated mice reveals its potential role in inflammatory and toxicological processes. These model-based studies help understand the functions of Cyp2j9 in disease-related conditions such as ALI and hepatotoxicity.

References:

1. Yang, Hui-Hui, Duan, Jia-Xi, Liu, Shao-Kun, Zhou, Yong, Guan, Cha-Xiang. 2020. A COX-2/sEH dual inhibitor PTUPB alleviates lipopolysaccharide-induced acute lung injury in mice by inhibiting NLRP3 inflammasome activation. In Theranostics, 10, 4749-4761. doi:10.7150/thno.43108. https://pubmed.ncbi.nlm.nih.gov/32308747/

2. Qu, W, Bradbury, J A, Tsao, C C, Rosenberg, R L, Zeldin, D C. 2001. Cytochrome P450 CYP2J9, a new mouse arachidonic acid omega-1 hydroxylase predominantly expressed in brain. In The Journal of biological chemistry, 276, 25467-79. doi:. https://pubmed.ncbi.nlm.nih.gov/11328810/

3. El-Ghiaty, Mahmoud A, Alqahtani, Mohammed A, El-Mahrouk, Sara R, Alammari, Ahmad H, El-Kadi, Ayman O S. 2024. Alteration of Hepatic Cytochrome P450 Expression and Arachidonic Acid Metabolism by Arsenic Trioxide (ATO) in C57BL/6 Mice. In Biological trace element research, 203, 1000-1015. doi:10.1007/s12011-024-04225-1. https://pubmed.ncbi.nlm.nih.gov/38758479/

4. Elshenawy, Osama H, Anwar-Mohamed, Anwar, Abdelhamid, Ghada, El-Kadi, Ayman O S. 2012. Murine atrial HL-1 cell line is a reliable model to study drug metabolizing enzymes in the heart. In Vascular pharmacology, 58, 326-33. doi:10.1016/j.vph.2012.12.002. https://pubmed.ncbi.nlm.nih.gov/23268359/

5. Baragatti, Barbara, Schwartzman, Michal Laniado, Angeloni, Debora, Luin, Stefano, Coceani, Flavio. 2009. EDHF function in the ductus arteriosus: evidence against involvement of epoxyeicosatrienoic acids and 12S-hydroxyeicosatetraenoic acid. In American journal of physiology. Heart and circulatory physiology, 297, H2161-8. doi:10.1152/ajpheart.00576.2009. https://pubmed.ncbi.nlm.nih.gov/19801493/