Urolithins Modulate the Viability, Autophagy, Apoptosis, and Nephrin Turnover in Podocytes Exposed to High Glucose
Urolithins are bioactive compounds generated in human and animal intestines because of the bacterial metabolism of dietary ellagitannins (and their constituent, ellagic acid). Due to their multidirectional effects, including anti-inflammatory, antioxidant, anti-cancer, neuroprotective, and antiglyca...
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MDPI AG
2022-08-01
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| author | Milena Kotewicz Mirosława Krauze-Baranowska Agnieszka Daca Agata Płoska Sylwia Godlewska Leszek Kalinowski Barbara Lewko |
| author_facet | Milena Kotewicz Mirosława Krauze-Baranowska Agnieszka Daca Agata Płoska Sylwia Godlewska Leszek Kalinowski Barbara Lewko |
| author_sort | Milena Kotewicz |
| collection | DOAJ |
| description | Urolithins are bioactive compounds generated in human and animal intestines because of the bacterial metabolism of dietary ellagitannins (and their constituent, ellagic acid). Due to their multidirectional effects, including anti-inflammatory, antioxidant, anti-cancer, neuroprotective, and antiglycative properties, urolithins are potential novel therapeutic agents. In this study, while considering the future possibility of using urolithins to improve podocyte function in diabetes, we assessed the results of exposing mouse podocytes cultured in normal (NG, 5.5 mM) and high (HG, 25 mM) glucose concentrations to urolithin A (UA) and urolithin B (UB). Podocytes metabolized UA to form glucuronides in a time-dependent manner; however, in HG conditions, the metabolism was lower than in NG conditions. In HG milieu, UA improved podocyte viability more efficiently than UB and reduced the reactive oxygen species level. Both types of urolithins showed cytotoxic activity at high (100 µM) concentration. The UA upregulated total and surface nephrin expression, which was paralleled by enhanced nephrin internalization. Regulation of nephrin turnover was independent of ambient glucose concentration. We conclude that UA affects podocytes in different metabolic and functional aspects. With respect to its pro-survival effects in HG-induced toxicity, UA could be considered as a potent therapeutic candidate against diabetic podocytopathy. |
| first_indexed | 2024-03-09T09:59:50Z |
| format | Article |
| id | doaj.art-c1a50570b0a84b4abc0215a6a348ff97 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T09:59:50Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-c1a50570b0a84b4abc0215a6a348ff972023-12-01T23:33:12ZengMDPI AGCells2073-44092022-08-011116247110.3390/cells11162471Urolithins Modulate the Viability, Autophagy, Apoptosis, and Nephrin Turnover in Podocytes Exposed to High GlucoseMilena Kotewicz0Mirosława Krauze-Baranowska1Agnieszka Daca2Agata Płoska3Sylwia Godlewska4Leszek Kalinowski5Barbara Lewko6Department of Pharmaceutical Pathophysiology, Faculty of Pharmacy, Medical University of Gdansk, 80-210 Gdansk, PolandDepartment of Pharmacognosy, Faculty of Pharmacy, Medical University of Gdansk, 80-210 Gdansk, PolandDepartment of Pathology and Experimental Rheumatology, Faculty of Medicine, Medical University of Gdansk, 80-210 Gdansk, PolandDepartment of Medical Laboratory Diagnostics-Fahrenheit Biobank BBMRI, Faculty of Pharmacy, Medical University of Gdansk, 80-210 Gdansk, PolandDepartment of Pharmacognosy, Faculty of Pharmacy, Medical University of Gdansk, 80-210 Gdansk, PolandDepartment of Medical Laboratory Diagnostics-Fahrenheit Biobank BBMRI, Faculty of Pharmacy, Medical University of Gdansk, 80-210 Gdansk, PolandDepartment of Pharmaceutical Pathophysiology, Faculty of Pharmacy, Medical University of Gdansk, 80-210 Gdansk, PolandUrolithins are bioactive compounds generated in human and animal intestines because of the bacterial metabolism of dietary ellagitannins (and their constituent, ellagic acid). Due to their multidirectional effects, including anti-inflammatory, antioxidant, anti-cancer, neuroprotective, and antiglycative properties, urolithins are potential novel therapeutic agents. In this study, while considering the future possibility of using urolithins to improve podocyte function in diabetes, we assessed the results of exposing mouse podocytes cultured in normal (NG, 5.5 mM) and high (HG, 25 mM) glucose concentrations to urolithin A (UA) and urolithin B (UB). Podocytes metabolized UA to form glucuronides in a time-dependent manner; however, in HG conditions, the metabolism was lower than in NG conditions. In HG milieu, UA improved podocyte viability more efficiently than UB and reduced the reactive oxygen species level. Both types of urolithins showed cytotoxic activity at high (100 µM) concentration. The UA upregulated total and surface nephrin expression, which was paralleled by enhanced nephrin internalization. Regulation of nephrin turnover was independent of ambient glucose concentration. We conclude that UA affects podocytes in different metabolic and functional aspects. With respect to its pro-survival effects in HG-induced toxicity, UA could be considered as a potent therapeutic candidate against diabetic podocytopathy.https://www.mdpi.com/2073-4409/11/16/2471podocytesurolithinsurolithin Ahigh glucosenephrindiabetic nephropathy |
| spellingShingle | Milena Kotewicz Mirosława Krauze-Baranowska Agnieszka Daca Agata Płoska Sylwia Godlewska Leszek Kalinowski Barbara Lewko Urolithins Modulate the Viability, Autophagy, Apoptosis, and Nephrin Turnover in Podocytes Exposed to High Glucose Cells podocytes urolithins urolithin A high glucose nephrin diabetic nephropathy |
| title | Urolithins Modulate the Viability, Autophagy, Apoptosis, and Nephrin Turnover in Podocytes Exposed to High Glucose |
| title_full | Urolithins Modulate the Viability, Autophagy, Apoptosis, and Nephrin Turnover in Podocytes Exposed to High Glucose |
| title_fullStr | Urolithins Modulate the Viability, Autophagy, Apoptosis, and Nephrin Turnover in Podocytes Exposed to High Glucose |
| title_full_unstemmed | Urolithins Modulate the Viability, Autophagy, Apoptosis, and Nephrin Turnover in Podocytes Exposed to High Glucose |
| title_short | Urolithins Modulate the Viability, Autophagy, Apoptosis, and Nephrin Turnover in Podocytes Exposed to High Glucose |
| title_sort | urolithins modulate the viability autophagy apoptosis and nephrin turnover in podocytes exposed to high glucose |
| topic | podocytes urolithins urolithin A high glucose nephrin diabetic nephropathy |
| url | https://www.mdpi.com/2073-4409/11/16/2471 |
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