Anserine and Carnosine Induce HSP70-Dependent H<sub>2</sub>S Formation in Endothelial Cells and Murine Kidney
Anserine and carnosine have nephroprotective actions; hydrogen sulfide (H<sub>2</sub>S) protects from ischemic tissue damage, and the underlying mechanisms are debated. In view of their common interaction with HSP70, we studied possible interactions of both dipeptides with H<sub>2&...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/1/66 |
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| author | Charlotte Wetzel Tilman Pfeffer Ruben Bulkescher Johanna Zemva Sergio Modafferi Alessandra Polimeni Angela Trovato Salinaro Vittorio Calabrese Claus Peter Schmitt Verena Peters |
| author_facet | Charlotte Wetzel Tilman Pfeffer Ruben Bulkescher Johanna Zemva Sergio Modafferi Alessandra Polimeni Angela Trovato Salinaro Vittorio Calabrese Claus Peter Schmitt Verena Peters |
| author_sort | Charlotte Wetzel |
| collection | DOAJ |
| description | Anserine and carnosine have nephroprotective actions; hydrogen sulfide (H<sub>2</sub>S) protects from ischemic tissue damage, and the underlying mechanisms are debated. In view of their common interaction with HSP70, we studied possible interactions of both dipeptides with H<sub>2</sub>S. H<sub>2</sub>S formation was measured in human proximal tubular epithelial cells (HK-2); three endothelial cell lines (HUVEC, HUAEC, MCEC); and in renal murine tissue of wild-type (WT), carnosinase-1 knockout <i>(Cndp1</i>-KO) and <i>Hsp70</i>-KO mice. Diabetes was induced by streptozocin. Incubation with carnosine increased H<sub>2</sub>S synthesis capacity in tubular cells, as well as with anserine in all three endothelial cell lines. H<sub>2</sub>S dose-dependently reduced anserine/carnosine degradation rate by serum and recombinant carnosinase-1 (CN1). Endothelial <i>Hsp70</i>-KO reduced H<sub>2</sub>S formation and abolished the stimulation by anserine and could be restored by <i>Hsp70</i> transfection. In female <i>Hsp70</i>-KO mice, kidney H<sub>2</sub>S formation was halved. In <i>Cndp1</i>-KO mice, kidney anserine concentrations were several-fold and sex-specifically increased. Kidney H<sub>2</sub>S formation capacity was increased 2–3-fold in female mice and correlated with anserine and carnosine concentrations. In diabetic <i>Cndp1</i>-KO mice, renal anserine and carnosine concentrations as well as H<sub>2</sub>S formation capacity were markedly reduced compared to non-diabetic <i>Cndp1</i>-KO littermates. Anserine and carnosine induce H<sub>2</sub>S formation in a cell-type and Hsp70-specific manner within a positive feedback loop with CN1. |
| first_indexed | 2024-03-09T13:47:31Z |
| format | Article |
| id | doaj.art-cbf7c018f8434f9390ef6096ec516f5d |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T13:47:31Z |
| publishDate | 2022-12-01 |
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| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-cbf7c018f8434f9390ef6096ec516f5d2023-11-30T20:57:51ZengMDPI AGAntioxidants2076-39212022-12-011216610.3390/antiox12010066Anserine and Carnosine Induce HSP70-Dependent H<sub>2</sub>S Formation in Endothelial Cells and Murine KidneyCharlotte Wetzel0Tilman Pfeffer1Ruben Bulkescher2Johanna Zemva3Sergio Modafferi4Alessandra Polimeni5Angela Trovato Salinaro6Vittorio Calabrese7Claus Peter Schmitt8Verena Peters9Centre for Pediatric and Adolescent Medicine, University Hospital Heidelberg, 69120 Heidelberg, GermanyCentre for Pediatric and Adolescent Medicine, University Hospital Heidelberg, 69120 Heidelberg, GermanyDepartment of Medicine I and Clinical Chemistry, Heidelberg University Hospital, 69120 Heidelberg, GermanyDepartment of Medicine I and Clinical Chemistry, Heidelberg University Hospital, 69120 Heidelberg, GermanyDepartment of Biomedical and Biotechnological Sciences, University of Catania, 95125 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, University of Catania, 95125 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, University of Catania, 95125 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, University of Catania, 95125 Catania, ItalyCentre for Pediatric and Adolescent Medicine, University Hospital Heidelberg, 69120 Heidelberg, GermanyCentre for Pediatric and Adolescent Medicine, University Hospital Heidelberg, 69120 Heidelberg, GermanyAnserine and carnosine have nephroprotective actions; hydrogen sulfide (H<sub>2</sub>S) protects from ischemic tissue damage, and the underlying mechanisms are debated. In view of their common interaction with HSP70, we studied possible interactions of both dipeptides with H<sub>2</sub>S. H<sub>2</sub>S formation was measured in human proximal tubular epithelial cells (HK-2); three endothelial cell lines (HUVEC, HUAEC, MCEC); and in renal murine tissue of wild-type (WT), carnosinase-1 knockout <i>(Cndp1</i>-KO) and <i>Hsp70</i>-KO mice. Diabetes was induced by streptozocin. Incubation with carnosine increased H<sub>2</sub>S synthesis capacity in tubular cells, as well as with anserine in all three endothelial cell lines. H<sub>2</sub>S dose-dependently reduced anserine/carnosine degradation rate by serum and recombinant carnosinase-1 (CN1). Endothelial <i>Hsp70</i>-KO reduced H<sub>2</sub>S formation and abolished the stimulation by anserine and could be restored by <i>Hsp70</i> transfection. In female <i>Hsp70</i>-KO mice, kidney H<sub>2</sub>S formation was halved. In <i>Cndp1</i>-KO mice, kidney anserine concentrations were several-fold and sex-specifically increased. Kidney H<sub>2</sub>S formation capacity was increased 2–3-fold in female mice and correlated with anserine and carnosine concentrations. In diabetic <i>Cndp1</i>-KO mice, renal anserine and carnosine concentrations as well as H<sub>2</sub>S formation capacity were markedly reduced compared to non-diabetic <i>Cndp1</i>-KO littermates. Anserine and carnosine induce H<sub>2</sub>S formation in a cell-type and Hsp70-specific manner within a positive feedback loop with CN1.https://www.mdpi.com/2076-3921/12/1/66anserinecarnosinediabetic nephropathyhydrogen sulfide |
| spellingShingle | Charlotte Wetzel Tilman Pfeffer Ruben Bulkescher Johanna Zemva Sergio Modafferi Alessandra Polimeni Angela Trovato Salinaro Vittorio Calabrese Claus Peter Schmitt Verena Peters Anserine and Carnosine Induce HSP70-Dependent H<sub>2</sub>S Formation in Endothelial Cells and Murine Kidney Antioxidants anserine carnosine diabetic nephropathy hydrogen sulfide |
| title | Anserine and Carnosine Induce HSP70-Dependent H<sub>2</sub>S Formation in Endothelial Cells and Murine Kidney |
| title_full | Anserine and Carnosine Induce HSP70-Dependent H<sub>2</sub>S Formation in Endothelial Cells and Murine Kidney |
| title_fullStr | Anserine and Carnosine Induce HSP70-Dependent H<sub>2</sub>S Formation in Endothelial Cells and Murine Kidney |
| title_full_unstemmed | Anserine and Carnosine Induce HSP70-Dependent H<sub>2</sub>S Formation in Endothelial Cells and Murine Kidney |
| title_short | Anserine and Carnosine Induce HSP70-Dependent H<sub>2</sub>S Formation in Endothelial Cells and Murine Kidney |
| title_sort | anserine and carnosine induce hsp70 dependent h sub 2 sub s formation in endothelial cells and murine kidney |
| topic | anserine carnosine diabetic nephropathy hydrogen sulfide |
| url | https://www.mdpi.com/2076-3921/12/1/66 |
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