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Effects of Roxadustat on Erythropoietin Production in the Rat Body

Anemia is a major complication of chronic renal failure. To treat this anemia, prolylhydroxylase domain enzyme (PHD) inhibitors as well as erythropoiesis-stimulating agents (ESAs) have been used. Although PHD inhibitors rapidly stimulate erythropoietin (Epo) production, the precise sites of Epo prod...

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Autores principales: Yasuoka, Yukiko, Izumi, Yuichiro, Fukuyama, Takashi, Omiya, Haruki, Pham, Truyen D., Inoue, Hideki, Oshima, Tomomi, Yamazaki, Taiga, Uematsu, Takayuki, Kobayashi, Noritada, Shimada, Yoshitaka, Nagaba, Yasushi, Yamashita, Tetsuro, Mukoyama, Masashi, Sato, Yuichi, Wall, Susan M., Sands, Jeff M., Takahashi, Noriko, Kawahara, Katsumasa, Nonoguchi, Hiroshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8838165/
https://www.ncbi.nlm.nih.gov/pubmed/35164384
http://dx.doi.org/10.3390/molecules27031119
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author Yasuoka, Yukiko
Izumi, Yuichiro
Fukuyama, Takashi
Omiya, Haruki
Pham, Truyen D.
Inoue, Hideki
Oshima, Tomomi
Yamazaki, Taiga
Uematsu, Takayuki
Kobayashi, Noritada
Shimada, Yoshitaka
Nagaba, Yasushi
Yamashita, Tetsuro
Mukoyama, Masashi
Sato, Yuichi
Wall, Susan M.
Sands, Jeff M.
Takahashi, Noriko
Kawahara, Katsumasa
Nonoguchi, Hiroshi
author_facet Yasuoka, Yukiko
Izumi, Yuichiro
Fukuyama, Takashi
Omiya, Haruki
Pham, Truyen D.
Inoue, Hideki
Oshima, Tomomi
Yamazaki, Taiga
Uematsu, Takayuki
Kobayashi, Noritada
Shimada, Yoshitaka
Nagaba, Yasushi
Yamashita, Tetsuro
Mukoyama, Masashi
Sato, Yuichi
Wall, Susan M.
Sands, Jeff M.
Takahashi, Noriko
Kawahara, Katsumasa
Nonoguchi, Hiroshi
author_sort Yasuoka, Yukiko
collection PubMed
description Anemia is a major complication of chronic renal failure. To treat this anemia, prolylhydroxylase domain enzyme (PHD) inhibitors as well as erythropoiesis-stimulating agents (ESAs) have been used. Although PHD inhibitors rapidly stimulate erythropoietin (Epo) production, the precise sites of Epo production following the administration of these drugs have not been identified. We developed a novel method for the detection of the Epo protein that employs deglycosylation-coupled Western blotting. With protein deglycosylation, tissue Epo contents can be quantified over an extremely wide range. Using this method, we examined the effects of the PHD inhibitor, Roxadustat (ROX), and severe hypoxia on Epo production in various tissues in rats. We observed that ROX increased Epo mRNA expression in both the kidneys and liver. However, Epo protein was detected in the kidneys but not in the liver. Epo protein was also detected in the salivary glands, spleen, epididymis and ovaries. However, both PHD inhibitors (ROX) and severe hypoxia increased the Epo protein abundance only in the kidneys. These data show that, while Epo is produced in many tissues, PHD inhibitors as well as severe hypoxia regulate Epo production only in the kidneys.
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spelling pubmed-88381652022-02-13 Effects of Roxadustat on Erythropoietin Production in the Rat Body Yasuoka, Yukiko Izumi, Yuichiro Fukuyama, Takashi Omiya, Haruki Pham, Truyen D. Inoue, Hideki Oshima, Tomomi Yamazaki, Taiga Uematsu, Takayuki Kobayashi, Noritada Shimada, Yoshitaka Nagaba, Yasushi Yamashita, Tetsuro Mukoyama, Masashi Sato, Yuichi Wall, Susan M. Sands, Jeff M. Takahashi, Noriko Kawahara, Katsumasa Nonoguchi, Hiroshi Molecules Article Anemia is a major complication of chronic renal failure. To treat this anemia, prolylhydroxylase domain enzyme (PHD) inhibitors as well as erythropoiesis-stimulating agents (ESAs) have been used. Although PHD inhibitors rapidly stimulate erythropoietin (Epo) production, the precise sites of Epo production following the administration of these drugs have not been identified. We developed a novel method for the detection of the Epo protein that employs deglycosylation-coupled Western blotting. With protein deglycosylation, tissue Epo contents can be quantified over an extremely wide range. Using this method, we examined the effects of the PHD inhibitor, Roxadustat (ROX), and severe hypoxia on Epo production in various tissues in rats. We observed that ROX increased Epo mRNA expression in both the kidneys and liver. However, Epo protein was detected in the kidneys but not in the liver. Epo protein was also detected in the salivary glands, spleen, epididymis and ovaries. However, both PHD inhibitors (ROX) and severe hypoxia increased the Epo protein abundance only in the kidneys. These data show that, while Epo is produced in many tissues, PHD inhibitors as well as severe hypoxia regulate Epo production only in the kidneys. MDPI 2022-02-08 /pmc/articles/PMC8838165/ /pubmed/35164384 http://dx.doi.org/10.3390/molecules27031119 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yasuoka, Yukiko
Izumi, Yuichiro
Fukuyama, Takashi
Omiya, Haruki
Pham, Truyen D.
Inoue, Hideki
Oshima, Tomomi
Yamazaki, Taiga
Uematsu, Takayuki
Kobayashi, Noritada
Shimada, Yoshitaka
Nagaba, Yasushi
Yamashita, Tetsuro
Mukoyama, Masashi
Sato, Yuichi
Wall, Susan M.
Sands, Jeff M.
Takahashi, Noriko
Kawahara, Katsumasa
Nonoguchi, Hiroshi
Effects of Roxadustat on Erythropoietin Production in the Rat Body
title Effects of Roxadustat on Erythropoietin Production in the Rat Body
title_full Effects of Roxadustat on Erythropoietin Production in the Rat Body
title_fullStr Effects of Roxadustat on Erythropoietin Production in the Rat Body
title_full_unstemmed Effects of Roxadustat on Erythropoietin Production in the Rat Body
title_short Effects of Roxadustat on Erythropoietin Production in the Rat Body
title_sort effects of roxadustat on erythropoietin production in the rat body
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8838165/
https://www.ncbi.nlm.nih.gov/pubmed/35164384
http://dx.doi.org/10.3390/molecules27031119
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