46-OR: A Novel Interaction between AT1 Receptor and Cytochrome-p450 Lipid Metabolites in Diabetic Retinopathy

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 46-OR
Author(s):  
MOHAMED AL-SHABRAWEY ◽  
AHMED IBRAHIM ◽  
AMANY M. TAWFIK ◽  
MONG HENG HENG WANG
Keyword(s):  
Diabetic Retinopathy ◽  
Cytochrome P450 ◽  
At1 Receptor ◽  
Lipid Metabolites

scholarly journals Cytochrome P450 monooxygenase lipid metabolites are significant second messengers in the resolution of choroidal neovascularization

2017 ◽  
Vol 114 (36) ◽  
pp. E7545-E7553 ◽  
Author(s):  
Eiichi Hasegawa ◽  
Saori Inafuku ◽  
Lama Mulki ◽  
Yoko Okunuki ◽  
Ryoji Yanai ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Choroidal Neovascularization ◽  
Vascular Function ◽  
Vision Loss ◽  
Second Messengers ◽  
Age Related Macular Degeneration ◽  
P450 Monooxygenase ◽  
Genetic Ablation ◽  
Age Related ◽  
Lipid Metabolites

Age-related macular degeneration (AMD) is the most common cause of blindness for individuals age 50 and above in the developed world. Abnormal growth of choroidal blood vessels, or choroidal neovascularization (CNV), is a hallmark of the neovascular (wet) form of advanced AMD and leads to significant vision loss. A growing body of evidence supports a strong link between neovascular disease and inflammation. Metabolites of long-chain polyunsaturated fatty acids derived from the cytochrome P450 (CYP) monooxygenase pathway serve as vital second messengers that regulate a number of hormones and growth factors involved in inflammation and vascular function. Using transgenic mice with altered CYP lipid biosynthetic pathways in a mouse model of laser-induced CNV, we characterized the role of these lipid metabolites in regulating neovascular disease. We discovered that the CYP-derived lipid metabolites epoxydocosapentaenoic acids (EDPs) and epoxyeicosatetraenoic acids (EEQs) are vital in dampening CNV severity. Specifically, overexpression of the monooxygenase CYP2C8 or genetic ablation or inhibition of the soluble epoxide hydrolase (sEH) enzyme led to increased levels of EDP and EEQ with attenuated CNV development. In contrast, when we promoted the degradation of these CYP-derived metabolites by transgenic overexpression of sEH, the protective effect against CNV was lost. We found that these molecules work in part through their ability to regulate the expression of key leukocyte adhesion molecules, on both leukocytes and endothelial cells, thereby mediating leukocyte recruitment. These results suggest that CYP lipid signaling molecules and their regulators are potential therapeutic targets in neovascular diseases.

Sex differences in the effect of cytochrome P450 2C19 polymorphisms on the risk of diabetic retinopathy

2013 ◽  
Vol 23 (12) ◽  
pp. 717-720 ◽  
Author(s):  
Ayami Kajiwara ◽  
Junji Saruwatari ◽  
Ayana Kita ◽  
Ryoko Kamihashi ◽  
Haruna Miyagawa ◽  
...  
Keyword(s):  
Sex Differences ◽  
Diabetic Retinopathy ◽  
Cytochrome P450 ◽  
Cytochrome P450 2C19

scholarly journals Identification of key lipid metabolites during metabolic dysregulation in the diabetic retinopathy disease mouse model and efficacy of Keluoxin capsule using an UHPLC-MS-based non-targeted lipidomics approach

RSC Advances ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 5491-5505
Author(s):  
Nan Ge ◽  
Ling Kong ◽  
Ai-hua Zhang ◽  
Ye Sun ◽  
Man-qian Zhao ◽  
...  
Keyword(s):  
Young Adults ◽  
Diabetic Retinopathy ◽  
Mouse Model ◽  
Metabolic Dysregulation ◽  
Important Complication ◽  
The World ◽  
Lipid Metabolites

Diabetic retinopathy (DR) is an important complication of diabetes, and is currently the main cause of blindness among young adults in the world.

Regulation of Cerebral Blood Flow: Response to Cytochrome P450 Lipid Metabolites

2018 ◽  
pp. 801-821 ◽  
Author(s):  
David R. Harder ◽  
Kevin R. Rarick ◽  
Debebe Gebremedhin ◽  
Susan S. Cohen
Keyword(s):  
Blood Flow ◽  
Cytochrome P450 ◽  
Cerebral Blood Flow ◽  
Blood Flow Response ◽  
Flow Response ◽  
Lipid Metabolites

Molecular evolution of a cytochrome P450 for the synthesis of potential antidepressant (2R,6R)-hydroxynorketamine

2021 ◽  
Author(s):  
Ansgar Bokel ◽  
Michael C. Hutter ◽  
Vlada B. Urlacher
Keyword(s):  
Cytochrome P450 ◽  
Molecular Evolution ◽  
Cytochrome P450 Monooxygenase ◽  
P450 Monooxygenase ◽  
Effective Synthesis

Engineered cytochrome P450 monooxygenase CYP154E1 enables the effective synthesis of the potential antidepressant (2R,6R)-hydroxynorketamine via N-demethylation and regio- and stereoselective hydroxylation of (R)-ketamine.

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