Seminar & Symposium/Entrance Exam info

2022-12-21

Cutting edge Seminar

 

 

Speaker:  Yukio Kato  (Professor, Laboratory of Molecular Pharmacotherapeutics, Faculty of Pharmacy, Kanazawa University)

Title:  Food-derived neurotrophic amino acid ergothioneine and its transporter SLC22A4

 

 

 Date&Time:  21 Dec.  (Wed.) 2022, 12:00- 13:00

※This seminar can also be attended through ZOOM. Please check the URL on “HIGO Cutting-Edge Seminar” at Moodle.

https://md.kumamoto-u.ac.jp/course/view.php?id=95315

 

 

Abstract:

Solute carrier SLC22A4 was originally identified as a transporter that is involved in the uptake of various organic cations in vitro and thus named carnitine/organic cation transporter 1 (OCTN1). We have constructed octn1 gene knockout mice (octn1-/-) and performed metabolome analysis using the mice to clarify its endogenous substrates in vivo, revealing that ergothioneine (ERGO) is present in blood and all organs of wild-type mice at µM to mM levels whereas octn1-/- does not have it in the body. ERGO is synthesized in fungi and mycobacteria, but not in mammals which ingest ERGO from dietary food. Thus, ERGO has its specific uptake transporter OCTN1 in the body, implying the important roles of this combination of transporter and substrate. So far, octn1-/- have been demonstrated to exhibit severe phenotypes compared with wild-type in disease models including liver fibrosis, chronic kidney disease, and intestinal inflammation, and expression of OCTN1 protein is up-regulated in those diseased organs, suggesting that this transporter and possibly its substrate may play protective roles in organ disease conditions. We also noticed that a highly water-soluble ERGO permeates the blood-brain barrier and is taken up by neurons and neural stem cells by OCTN1. ERGO induces expression of brain-derived neurotrophic factor (BDNF) and neurotrophin 5 (NT5) through amino acid signaling in the brain, promoting their receptor TrkB phosphorylation and differentiation of neural stem cells into neurons. Oral administration of ERGO for 2 weeks improved learning and memory ability in mice. Notably, this effect was observed at systemic ERGO concentration relevant to that in humans, promoting the clinical application of this compound. So far, at least two human studies have been performed to show that ingestion of food-derived and pure ERGO improves verbal memory and sleep difficulties in healthy volunteers. Oral administration of ERGO also prevented cognitive decline at least partially via the promotion of neurogenesis in Alzheimer’s disease mice. Thus, ERGO may be not only be applicable to healthy foods, but also to the prevention of neurodegenerative disease.

 

References:

Katsube M., et al. J Functional Foods. 95: 105165 (2022)

Nakamichi N., et al. Curr Mol Pharmacol. 14(2): 220-233 (2021)

渡邉憲和他. 薬理と治療 48(4): 685-697 (2020)

Ishimoto T et al. Cell Signal. 53: 269-280 (2019)

Ishimoto T., et al. Neurochem Res. 43(1): 107-119 (2018)

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