Protective Cellular Mechanism of Estrogen Against Kidney Stone Formation: A Proteomics Approach and Functional Validation
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Females have less incidence/prevalence of kidney stone disease than males. Estrogen thus may serve as the protective factor but with unclear mechanism. This study explores cellular mechanism underlying such stone preventive mechanism of estroge...
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th-mahidol.500592020-01-27T14:37:46Z Protective Cellular Mechanism of Estrogen Against Kidney Stone Formation: A Proteomics Approach and Functional Validation Paleerath Peerapen Visith Thongboonkerd Faculty of Medicine, Siriraj Hospital, Mahidol University Biochemistry, Genetics and Molecular Biology © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Females have less incidence/prevalence of kidney stone disease than males. Estrogen thus may serve as the protective factor but with unclear mechanism. This study explores cellular mechanism underlying such stone preventive mechanism of estrogen. Madin darby canine kidney (MDCK) renal tubular cells are incubated with or without 20 nm 17β-estradiol for 7 days. Comparative proteomics reveals 58 differentially expressed proteins in estrogen-treated versus control cells that are successfully identified by nanoLC–ESI–Q-TOF-MS/MS. Interestingly, these altered proteins are involved mainly in “binding and receptor,” “metabolic process,” and “migration and healing” networks. Functional investigations demonstrate reduction of calcium oxalate (CaOx) crystal-binding capability of the estrogen-treated cells consistent with the decreased levels of annexin A1 and α-enolase (the known CaOx crystal-binding receptors) on the cell surface. High-calcium and high-oxalate challenge initially enhances surface expression of annexin A1 and α-enolase, respectively, both of which return to their basal levels by estrogen. Additionally, estrogen reduces intracellular ATP level and promotes cell migration and tissue healing. Taken together, estrogen causes changes in cellular proteome of renal tubular cells that lead to decreased surface expression of CaOx crystal receptors, reduced intracellular metabolism, and enhanced cell proliferation and tissue healing, all of which may contribute, at least in part, to stone prevention. 2020-01-27T07:37:46Z 2020-01-27T07:37:46Z 2019-10-01 Article Proteomics. Vol.19, No.19 (2019) 10.1002/pmic.201900095 16159861 16159853 2-s2.0-85072792051 https://repository.li.mahidol.ac.th/handle/123456789/50059 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85072792051&origin=inward |
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Biochemistry, Genetics and Molecular Biology Paleerath Peerapen Visith Thongboonkerd Protective Cellular Mechanism of Estrogen Against Kidney Stone Formation: A Proteomics Approach and Functional Validation |
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© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Females have less incidence/prevalence of kidney stone disease than males. Estrogen thus may serve as the protective factor but with unclear mechanism. This study explores cellular mechanism underlying such stone preventive mechanism of estrogen. Madin darby canine kidney (MDCK) renal tubular cells are incubated with or without 20 nm 17β-estradiol for 7 days. Comparative proteomics reveals 58 differentially expressed proteins in estrogen-treated versus control cells that are successfully identified by nanoLC–ESI–Q-TOF-MS/MS. Interestingly, these altered proteins are involved mainly in “binding and receptor,” “metabolic process,” and “migration and healing” networks. Functional investigations demonstrate reduction of calcium oxalate (CaOx) crystal-binding capability of the estrogen-treated cells consistent with the decreased levels of annexin A1 and α-enolase (the known CaOx crystal-binding receptors) on the cell surface. High-calcium and high-oxalate challenge initially enhances surface expression of annexin A1 and α-enolase, respectively, both of which return to their basal levels by estrogen. Additionally, estrogen reduces intracellular ATP level and promotes cell migration and tissue healing. Taken together, estrogen causes changes in cellular proteome of renal tubular cells that lead to decreased surface expression of CaOx crystal receptors, reduced intracellular metabolism, and enhanced cell proliferation and tissue healing, all of which may contribute, at least in part, to stone prevention. |
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Faculty of Medicine, Siriraj Hospital, Mahidol University |
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Faculty of Medicine, Siriraj Hospital, Mahidol University Paleerath Peerapen Visith Thongboonkerd |
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Article |
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Paleerath Peerapen Visith Thongboonkerd |
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Paleerath Peerapen |
title |
Protective Cellular Mechanism of Estrogen Against Kidney Stone Formation: A Proteomics Approach and Functional Validation |
title_short |
Protective Cellular Mechanism of Estrogen Against Kidney Stone Formation: A Proteomics Approach and Functional Validation |
title_full |
Protective Cellular Mechanism of Estrogen Against Kidney Stone Formation: A Proteomics Approach and Functional Validation |
title_fullStr |
Protective Cellular Mechanism of Estrogen Against Kidney Stone Formation: A Proteomics Approach and Functional Validation |
title_full_unstemmed |
Protective Cellular Mechanism of Estrogen Against Kidney Stone Formation: A Proteomics Approach and Functional Validation |
title_sort |
protective cellular mechanism of estrogen against kidney stone formation: a proteomics approach and functional validation |
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2020 |
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https://repository.li.mahidol.ac.th/handle/123456789/50059 |
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1763493200936304640 |