Tags

Type your tag names separated by a space and hit enter

Impairment of the carnitine/organic cation transporter 1-ergothioneine axis is mediated by intestinal transporter dysfunction in chronic kidney disease.
Kidney Int. 2017 12; 92(6):1356-1369.KI

Abstract

Carnitine/organic cation transporter 1 (OCTN1) is a specific transporter of the food-derived antioxidant ergothioneine. Ergothioneine is absorbed by intestinal OCTN1, distributed through the bloodstream, and incorporated into each organ by OCTN1. OCTN1 expression is upregulated in injured tissues, and promotes ergothioneine uptake to reduce further damage caused by oxidative stress. However, the role of the OCTN1-ergothioneine axis in kidney-intestine cross-talk and chronic kidney disease (CKD) progression remains unclear. Here we assessed ergothioneine uptake via intestinal OCTN1 and confirmed the expression of OCTN1. The ability of OCTN1 to absorb ergothioneine was diminished in mice with CKD. In combination with OCTN1 dysfunction, OCTN1 localization on the intestinal apical cellular membrane was disturbed in mice with CKD. Proteomic analysis, RT-PCR, Western blotting, and immunohistochemistry revealed that PDZ (PSD95, Dlg, and ZO1), a PDZK1 domain-containing protein that regulates the localization of transporters, was decreased in mice with CKD. Decreased intestinal ergothioneine uptake from food decreased ergothioneine levels in the blood of mice with CKD. Despite increased OCTN1 expression and ergothioneine uptake into the kidneys of mice with CKD, ergothioneine levels did not increase. To identify the role of the OCTN1-ergothioneine axis in CKD, we evaluated kidney damage and oxidative stress in OCTN1-knockout mice with CKD and found that kidney fibrosis worsened. Oxidative stress indicators were increased in OCTN1-knockout mice. Moreover, ergothioneine levels in the blood of patients with CKD decreased, which were restored after kidney transplantation. Thus, a novel inter-organ interaction mediated by transporters is associated with CKD progression.

Authors+Show Affiliations

Division of Nephrology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan.Division of Nephrology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan. Electronic address: kfuruichi@m-kanazawa.jp.Division of Nephrology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan.Division of Nephrology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan.Division of Nephrology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan; Department of Environmental and Preventive Medicine, Kanazawa University, Kanazawa, Ishikawa, Japan.Division of Nephrology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan.Division of Nephrology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan.Division of Nephrology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan.Department of System Biology, Kanazawa University, Kanazawa, Ishikawa, Japan.Department of Bio-System Pharmacology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.Department of Bio-System Pharmacology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.Department of Bio-System Pharmacology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Science, Kanazawa University, Kanazawa, Ishikawa, Japan.Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Science, Kanazawa University, Kanazawa, Ishikawa, Japan.Division of Nephrology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan; Department of Nephrology and Laboratory Medicine, Kanazawa, Ishikawa, Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28754554

Citation

Shinozaki, Yasuyuki, et al. "Impairment of the Carnitine/organic Cation Transporter 1-ergothioneine Axis Is Mediated By Intestinal Transporter Dysfunction in Chronic Kidney Disease." Kidney International, vol. 92, no. 6, 2017, pp. 1356-1369.
Shinozaki Y, Furuichi K, Toyama T, et al. Impairment of the carnitine/organic cation transporter 1-ergothioneine axis is mediated by intestinal transporter dysfunction in chronic kidney disease. Kidney Int. 2017;92(6):1356-1369.
Shinozaki, Y., Furuichi, K., Toyama, T., Kitajima, S., Hara, A., Iwata, Y., Sakai, N., Shimizu, M., Kaneko, S., Isozumi, N., Nagamori, S., Kanai, Y., Sugiura, T., Kato, Y., & Wada, T. (2017). Impairment of the carnitine/organic cation transporter 1-ergothioneine axis is mediated by intestinal transporter dysfunction in chronic kidney disease. Kidney International, 92(6), 1356-1369. https://doi.org/10.1016/j.kint.2017.04.032
Shinozaki Y, et al. Impairment of the Carnitine/organic Cation Transporter 1-ergothioneine Axis Is Mediated By Intestinal Transporter Dysfunction in Chronic Kidney Disease. Kidney Int. 2017;92(6):1356-1369. PubMed PMID: 28754554.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impairment of the carnitine/organic cation transporter 1-ergothioneine axis is mediated by intestinal transporter dysfunction in chronic kidney disease. AU - Shinozaki,Yasuyuki, AU - Furuichi,Kengo, AU - Toyama,Tadashi, AU - Kitajima,Shinji, AU - Hara,Akinori, AU - Iwata,Yasunori, AU - Sakai,Norihiko, AU - Shimizu,Miho, AU - Kaneko,Shuichi, AU - Isozumi,Noriyoshi, AU - Nagamori,Shushi, AU - Kanai,Yoshikatsu, AU - Sugiura,Tomoko, AU - Kato,Yukio, AU - Wada,Takashi, Y1 - 2017/07/26/ PY - 2016/10/08/received PY - 2017/04/03/revised PY - 2017/04/18/accepted PY - 2017/7/30/pubmed PY - 2018/7/6/medline PY - 2017/7/30/entrez KW - chronic kidney disease KW - fibrosis KW - oxidative stress SP - 1356 EP - 1369 JF - Kidney international JO - Kidney Int VL - 92 IS - 6 N2 - Carnitine/organic cation transporter 1 (OCTN1) is a specific transporter of the food-derived antioxidant ergothioneine. Ergothioneine is absorbed by intestinal OCTN1, distributed through the bloodstream, and incorporated into each organ by OCTN1. OCTN1 expression is upregulated in injured tissues, and promotes ergothioneine uptake to reduce further damage caused by oxidative stress. However, the role of the OCTN1-ergothioneine axis in kidney-intestine cross-talk and chronic kidney disease (CKD) progression remains unclear. Here we assessed ergothioneine uptake via intestinal OCTN1 and confirmed the expression of OCTN1. The ability of OCTN1 to absorb ergothioneine was diminished in mice with CKD. In combination with OCTN1 dysfunction, OCTN1 localization on the intestinal apical cellular membrane was disturbed in mice with CKD. Proteomic analysis, RT-PCR, Western blotting, and immunohistochemistry revealed that PDZ (PSD95, Dlg, and ZO1), a PDZK1 domain-containing protein that regulates the localization of transporters, was decreased in mice with CKD. Decreased intestinal ergothioneine uptake from food decreased ergothioneine levels in the blood of mice with CKD. Despite increased OCTN1 expression and ergothioneine uptake into the kidneys of mice with CKD, ergothioneine levels did not increase. To identify the role of the OCTN1-ergothioneine axis in CKD, we evaluated kidney damage and oxidative stress in OCTN1-knockout mice with CKD and found that kidney fibrosis worsened. Oxidative stress indicators were increased in OCTN1-knockout mice. Moreover, ergothioneine levels in the blood of patients with CKD decreased, which were restored after kidney transplantation. Thus, a novel inter-organ interaction mediated by transporters is associated with CKD progression. SN - 1523-1755 UR - https://www.unboundmedicine.com/medline/citation/28754554/Impairment_of_the_carnitine/organic_cation_transporter_1_ergothioneine_axis_is_mediated_by_intestinal_transporter_dysfunction_in_chronic_kidney_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0085-2538(17)30332-0 DB - PRIME DP - Unbound Medicine ER -