Cyp2c23-KO Mouse

Cyp2c23, a member of the cytochrome P450 2C subfamily, is constitutively expressed in rat liver and kidney. It functions as an arachidonic acid epoxygenase, efficiently producing epoxyeicosatrienoic acids (EETs) such as 8,9-EET, 11,12-EET, and 14,15-EET in the kidney [2]. These EETs are involved in regulating renal vascular tone, salt excretion, and have anti-inflammatory properties. The gene is also important in the context of various physiological and pathological processes in rats [3,4,5].

In rats, low Na intake downregulates the activity and expression of Cyp2c23 in the thick ascending limb and collecting duct of the kidney, attenuating the inhibitory effect of arachidonic acid on epithelial Na channels and Na transport [1]. A peroxisome proliferator-activated receptor-α activator, fenofibrate, can induce renal Cyp2c23 protein and AA-epoxygenase activity, protecting against angiotensin II-induced renal injury [3]. In a rodent model of septic shock, increased Cyp2c23 expression is associated with the protective effect of 5,14-HEDGE against hypotension, tachycardia, inflammation, and mortality [4]. Also, in salt-sensitive hypertension, tumor necrosis factor alpha blockade increases renal Cyp2c23 expression and slows the progression of renal damage [5].

In conclusion, Cyp2c23 plays crucial roles in renal function, blood pressure regulation, and inflammation-related processes in rats. These functions are revealed through in-vivo studies in rats, which are important research models. Understanding Cyp2c23's functions provides insights into the mechanisms underlying diseases related to renal function and blood pressure regulation, potentially guiding the development of new therapeutic strategies.

References:

1. Sun, Peng, Lin, Dao-Hong, Wang, Tong, Nasjletti, Alberto, Wang, Wen-Hui. 2006. Low Na intake suppresses expression of CYP2C23 and arachidonic acid-induced inhibition of ENaC. In American journal of physiology. Renal physiology, 291, F1192-200. doi:. https://pubmed.ncbi.nlm.nih.gov/16849695/

2. Imaoka, S, Wedlund, P J, Ogawa, H, Gonzalez, F J, Kim, H Y. . Identification of CYP2C23 expressed in rat kidney as an arachidonic acid epoxygenase. In The Journal of pharmacology and experimental therapeutics, 267, 1012-6. doi:. https://pubmed.ncbi.nlm.nih.gov/8246128/

3. Muller, Dominik N, Theuer, Juergen, Shagdarsuren, Erdenechimeg, Luft, Friedrich C, Schunck, Wolf-Hagen. . A peroxisome proliferator-activated receptor-alpha activator induces renal CYP2C23 activity and protects from angiotensin II-induced renal injury. In The American journal of pathology, 164, 521-32. doi:. https://pubmed.ncbi.nlm.nih.gov/14742258/

4. Tunctan, Bahar, Korkmaz, Belma, Sari, Ayse Nihal, Falck, John R, Malik, Kafait U. 2013. 5,14-HEDGE, a 20-HETE mimetic, reverses hypotension and improves survival in a rodent model of septic shock: contribution of soluble epoxide hydrolase, CYP2C23, MEK1/ERK1/2/IKKβ/IκB-α/NF-κB pathway, and proinflammatory cytokine formation. In Prostaglandins & other lipid mediators, 102-103, 31-41. doi:10.1016/j.prostaglandins.2013.01.005. https://pubmed.ncbi.nlm.nih.gov/23454652/

5. Elmarakby, Ahmed A, Quigley, Jeffrey E, Pollock, David M, Imig, John D. 2006. Tumor necrosis factor alpha blockade increases renal Cyp2c23 expression and slows the progression of renal damage in salt-sensitive hypertension. In Hypertension (Dallas, Tex. : 1979), 47, 557-62. doi:. https://pubmed.ncbi.nlm.nih.gov/16415373/