Homostachydrine is a Xenobiotic Substrate of OCTN1/SLC22A4 and Potentially Sensitizes Pentylenetetrazole-Induced Seizures in Mice

Nishiyama, Misa; Nakamichi, Noritaka; Yoshimura, Tetsuzo; Masuo, Yusuke; Komori, Tomoe; Ishimoto, Takahiro; Matsuo, Jun‐ichi; Kato, Yukio

doi:10.1007/s11064-020-03118-8

Cited by 10 publications

(13 citation statements)

References 45 publications

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“…Here, the driving force of the Na + gradient is missing. Not surprisingly, homostachydrine was also recently found as a substrate [74]: homostachydrine differs from stachydrine in the ring by only one CH 2 group (Fig. 1).…”

Section: The Point Of This Reviewmentioning

confidence: 71%

The ergothioneine transporter (ETT): substrates and locations, an inventory

2022

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In all vertebrates including mammals, the ergothioneine transporter ETT (obsolete name OCTN1; human gene symbol SLC22A4) is a powerful and highly specific transporter for the uptake of ergothioneine (ET). ETT is not expressed ubiquitously and only cells with high ETT cell‐surface levels can accumulate ET to high concentration. Without ETT, there is no uptake because the plasma membrane is essentially impermeable to this hydrophilic zwitterion. Here, we review the substrate specificity and localization of ETT, which is prominently expressed in neutrophils, monocytes/macrophages, and developing erythrocytes. Most sites of strong expression are conserved across species, but there are also major differences. In particular, we critically analyze the evidence for the expression of ETT in the brain as well as recent data suggesting that the transporter SLC22A15 may also transport ET. We conclude that, to date, ETT remains the only well‐defined biomarker for intracellular ET activity. In humans, the ability to take up, distribute, and retain ET depends principally on this transporter.

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Section: The Point Of This Reviewmentioning

confidence: 71%

The ergothioneine transporter (ETT): substrates and locations, an inventory

2022

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“…It was discovered in 2005 that OCTN1 (encoded by the gene slc22a4 ) is primarily a transporter for ET, with higher transport efficiency than many other related metabolites [ 5 ], and without it (as seen in knockout animal models) there is an absence of ET in cells and tissues [ 8 , 9 ]. From the initial notion that OCTN1 primarily serves as an ET transporter, numerous other studies surfaced declaring that OCTN1 was involved in the transport of compounds such as nucleosides [ 10 ], acetylcholine [ 11 ], tetraethylammonium, spermine, l -carnitine, sulpiride, homostachydrine [ 12 ], cytarabine, gemcitabine, gabapentin, oxaliplatin, and metformin. However, many of these claims used unconventional models that were far from physiological.…”

Section: The Ergothioneine Transportermentioning

confidence: 99%

“…Another neurological condition, epilepsy, characterized by abnormal electrical-mediated activity in the brain leading to recurrent seizures, was found to be exacerbated by OCTN1 uptake of homostachydrine in the brain of mouse models [ 12 ]. However, ET administration to these mice decreased homostachydrine uptake in the brain (presumably through competing transport of ET) leading to decreased seizures and prolonged survival of the animals [ 12 ]. Glutamate receptor-mediated hyperexcitation plays a key role in seizures, but a study demonstrated that ET protected rat retinal neurons against N-methyl- d -aspartate excitotoxicity [ 116 ].…”

Section: A Gerontological Perspectivementioning

confidence: 99%

Ergothioneine, recent developments

2021

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There has been a recent surge of interest in the unique low molecular weight dietary thiol/thione, ergothioneine. This compound can accumulate at high levels in the body from diet and may play important physiological roles in human health and development, and possibly in prevention and treatment of disease. Blood levels of ergothioneine decline with age and onset of various diseases. Here we highlight recent advances in our knowledge of ergothioneine.

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“…An apical intestinal localization has been suggested as well [ 41 ] and PDZ-containing kidney protein (PDZK) interaction would corroborate this localization [ 42 ]. On the basis of relative abundance data, some authors revealed that region specific expression was highest in the proximal jejunum and lowest in the colon [ 43 ]. However, more detailed data would be necessary to unequivocally assess the intestinal OCTN1 sub-localization.…”

Section: Tissue Expression/localization Of Octn1mentioning

confidence: 99%

OCTN1: A Widely Studied but Still Enigmatic Organic Cation Transporter Linked to Human Pathology and Drug Interactions

Pochini

Galluccio

Scalise

et al. 2022

IJMS

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The Novel Organic Cation Transporter, OCTN1, is the first member of the OCTN subfamily; it belongs to the wider Solute Carrier family SLC22, which counts many members including cation and anion organic transporters. The tertiary structure has not been resolved for any cation organic transporter. The functional role of OCNT1 is still not well assessed despite the many functional studies so far conducted. The lack of a definitive identification of OCTN1 function can be attributed to the different experimental systems and methodologies adopted for studying each of the proposed ligands. Apart from the contradictory data, the international scientific community agrees on a role of OCTN1 in protecting cells and tissues from oxidative and/or inflammatory damage. Moreover, the involvement of this transporter in drug interactions and delivery has been well clarified, even though the exact profile of the transported/interacting molecules is still somehow confusing. Therefore, OCTN1 continues to be a hot topic in terms of its functional role and structure. This review focuses on the most recent advances on OCTN1 in terms of functional aspects, physiological roles, substrate specificity, drug interactions, tissue expression, and relationships with pathology.

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Homostachydrine is a Xenobiotic Substrate of OCTN1/SLC22A4 and Potentially Sensitizes Pentylenetetrazole-Induced Seizures in Mice

Cited by 10 publications

References 45 publications

The ergothioneine transporter (ETT): substrates and locations, an inventory

The ergothioneine transporter (ETT): substrates and locations, an inventory

Ergothioneine, recent developments

OCTN1: A Widely Studied but Still Enigmatic Organic Cation Transporter Linked to Human Pathology and Drug Interactions

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