Session information

Symposium

[S34] Impact of catechol-O-methyltransferase (COMT) defficiency on metabolic syndrome-related diseases and renal-heart-vascular dysfunction

Sat. Mar 30, 2024 9:45 AM - 11:45 AM [Room 419] Conference Center 419 (4F)

Organizer: Hiroshi Iijima (Nihon Univ. Sch. Pharm.), Keizo Kanasaki (Shimane Univ. Faculty. Med.)

Reduced catechol-O-methyltransferase (COMT) activity is deemed involved in many diseases, including metabolic syndrome, diabetics, hypertension, chronic kidney disease, arteriosclerosis, intracerebral hemorrhage, and ischemic myocardial infarction.
COMT is recognized as an enzyme that deactivates and removes catecholamines, such as dopamine and noradrenaline. Nevertheless, COMT functions as the pivotal enzyme responsible for transforming 2-hydroxyestradiol into its active form, 2-methoxyestradiol (2-ME) which plays a crucial role in vascular homeostasis by suppressing the signaling of the hypoxia-inducible factor-1 alpha (HIF-1α).
Several animal experiments, involving knockout mice and COMT low-activity mice, have revealed that COMT deficiency is linked to conditions such as preeclampsia and diabetes. Moreover, the administration of 2-ME was able to alleviate the associated symptoms. Despite these findings, the connection between COMT and these diseases is not yet widely studied.
Against this backdrop, this symposium would provide a comprehensive overview on the correlation between COMT and diseases from the field of medicine, as well as research results on small-molecule COMT enhancers and inhibitors from the field of medicinal chemistry.

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はじめに (9:45 AM - 9:55 AM)

9:55 AM - 10:15 AM

[S34-1] COMT deficiency: the relevant pathophysiology and therapeutic target

○Keizo Kanasaki^1,2 (1. Shimane Univ. Faculty Medicine., 2. Integrated Kidney Research and Advance, Shimane Univ. Faculty. Medicine.)

10:15 AM - 10:35 AM

[S34-2] COMT deficiency and pregnancy complication

○Asako Kumagai¹, Keizo Kanasaki² (1. Juntendo Univ. Dept. Obstetrics and Gynecology., 2. Shimane Univ. Faculty. Medicine.)

10:35 AM - 10:55 AM

[S34-3] Discovery and characterization of enhancer molecules for COMT

○Hiroshi Iijima^1,2, Hiroaki Saito¹, Norio Niwa¹, Hiroko Kobayashi¹, Tomoko Takamiya¹, Tadahiro Yahagi¹, Kei -ichi Matsuzaki¹ (1. Nihon Univ. Sch. Pharmacy., 2. CBI Research Inst.)

10:55 AM - 11:15 AM

[S34-4] Reaction mechanism of COMT and conformational changes induced by enhancer molecules.

○Katsuki Takebe¹, Takao Kuwada-Kusunose², Mamoru Suzuki³, Hiroshi Iijima^4,5 (1. Grad. Sch. Dent., Osaka Univ., 2. Nihon Univ. Sch. Dentistry, Matsudo., 3. Inst. Protein Research, Osaka Univ., 4. Nihon Univ. Sch. Pharmacy., 5. CBI Research Inst.)

11:15 AM - 11:35 AM

[S34-5] COMT-Ligand Molecular Interactions Based on Crystal Structures and Quantum Chemical Calculations

○Kaori Fukuzawa^1,2, Satoko Shirai², Katsuki Takebe³, Daisuke Takaya¹, Hiroshi Iijima^4,5 (1. Grad. Sch. Pharm. Sci., Osaka Univ., 2. Sch. Pharm., Hoshi Univ., 3. Grad. Sch. Dent., Osaka Univ., 4. Nihon Univ. Sch. Pharmacy., 5. CBI Research Inst.)