Thiosulfate sulfurtransferase prevents hyperglycemic damage to the zebrafish pronephros in an experimental model for diabetes
Abstract Thiosulfate sulfurtransferase (TST, EC 2.8.1.1), also known as Rhodanese, was initially discovered as a cyanide detoxification enzyme. However, it was recently also found to be a genetic predictor of resistance to obesity-related type 2 diabetes. Diabetes type 2 is characterized by progress...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-16320-1 |
| _version_ | 1818510912268533760 |
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| author | Zayana M. Al-Dahmani Xiaogang Li Lucas M. Wiggenhauser Hannes Ott Paul D. Kruithof Sergey Lunev Fernando A. Batista Yang Luo Amalia M. Dolga Nicholas M. Morton Matthew R. Groves Jens Kroll Harry van Goor |
| author_facet | Zayana M. Al-Dahmani Xiaogang Li Lucas M. Wiggenhauser Hannes Ott Paul D. Kruithof Sergey Lunev Fernando A. Batista Yang Luo Amalia M. Dolga Nicholas M. Morton Matthew R. Groves Jens Kroll Harry van Goor |
| author_sort | Zayana M. Al-Dahmani |
| collection | DOAJ |
| description | Abstract Thiosulfate sulfurtransferase (TST, EC 2.8.1.1), also known as Rhodanese, was initially discovered as a cyanide detoxification enzyme. However, it was recently also found to be a genetic predictor of resistance to obesity-related type 2 diabetes. Diabetes type 2 is characterized by progressive loss of adequate β-cell insulin secretion and onset of insulin resistance with increased insulin demand, which contributes to the development of hyperglycemia. Diabetic complications have been replicated in adult hyperglycemic zebrafish, including retinopathy, nephropathy, impaired wound healing, metabolic memory, and sensory axonal degeneration. Pancreatic and duodenal homeobox 1 (Pdx1) is a key component in pancreas development and mature beta cell function and survival. Pdx1 knockdown or knockout in zebrafish induces hyperglycemia and is accompanied by organ alterations similar to clinical diabetic retinopathy and diabetic nephropathy. Here we show that pdx1-knockdown zebrafish embryos and larvae survived after incubation with thiosulfate and no obvious morphological alterations were observed. Importantly, incubation with hTST and thiosulfate rescued the hyperglycemic phenotype in pdx1-knockdown zebrafish pronephros. Activation of the mitochondrial TST pathway might be a promising option for therapeutic intervention in diabetes and its organ complications. |
| first_indexed | 2024-12-10T23:26:32Z |
| format | Article |
| id | doaj.art-a6076927b73a465a973c4cbec05c6ca7 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-10T23:26:32Z |
| publishDate | 2022-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-a6076927b73a465a973c4cbec05c6ca72022-12-22T01:29:35ZengNature PortfolioScientific Reports2045-23222022-07-011211710.1038/s41598-022-16320-1Thiosulfate sulfurtransferase prevents hyperglycemic damage to the zebrafish pronephros in an experimental model for diabetesZayana M. Al-Dahmani0Xiaogang Li1Lucas M. Wiggenhauser2Hannes Ott3Paul D. Kruithof4Sergey Lunev5Fernando A. Batista6Yang Luo7Amalia M. Dolga8Nicholas M. Morton9Matthew R. Groves10Jens Kroll11Harry van Goor12Department of Pharmacy and Drug Design, University of GroningenDepartment of Vascular Biology and Tumor Angiogenesis, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg UniversityDepartment of Vascular Biology and Tumor Angiogenesis, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg UniversityDepartment of Vascular Biology and Tumor Angiogenesis, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg UniversityDepartment of Pharmacy and Drug Design, University of GroningenDepartment of Pharmacy and Drug Design, University of GroningenDepartment of Pharmacy and Drug Design, University of GroningenDepartment of Pharmacy, Molecular Pharmacology, University of GroningenDepartment of Pharmacy, Molecular Pharmacology, University of GroningenCentre for Cardiovascular Science, The Queen’s Medical Research Institute, University of EdinburghDepartment of Pharmacy and Drug Design, University of GroningenDepartment of Vascular Biology and Tumor Angiogenesis, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg UniversityDepartment of Pathology and Medical Biology, University Medical Center GroningenAbstract Thiosulfate sulfurtransferase (TST, EC 2.8.1.1), also known as Rhodanese, was initially discovered as a cyanide detoxification enzyme. However, it was recently also found to be a genetic predictor of resistance to obesity-related type 2 diabetes. Diabetes type 2 is characterized by progressive loss of adequate β-cell insulin secretion and onset of insulin resistance with increased insulin demand, which contributes to the development of hyperglycemia. Diabetic complications have been replicated in adult hyperglycemic zebrafish, including retinopathy, nephropathy, impaired wound healing, metabolic memory, and sensory axonal degeneration. Pancreatic and duodenal homeobox 1 (Pdx1) is a key component in pancreas development and mature beta cell function and survival. Pdx1 knockdown or knockout in zebrafish induces hyperglycemia and is accompanied by organ alterations similar to clinical diabetic retinopathy and diabetic nephropathy. Here we show that pdx1-knockdown zebrafish embryos and larvae survived after incubation with thiosulfate and no obvious morphological alterations were observed. Importantly, incubation with hTST and thiosulfate rescued the hyperglycemic phenotype in pdx1-knockdown zebrafish pronephros. Activation of the mitochondrial TST pathway might be a promising option for therapeutic intervention in diabetes and its organ complications.https://doi.org/10.1038/s41598-022-16320-1 |
| spellingShingle | Zayana M. Al-Dahmani Xiaogang Li Lucas M. Wiggenhauser Hannes Ott Paul D. Kruithof Sergey Lunev Fernando A. Batista Yang Luo Amalia M. Dolga Nicholas M. Morton Matthew R. Groves Jens Kroll Harry van Goor Thiosulfate sulfurtransferase prevents hyperglycemic damage to the zebrafish pronephros in an experimental model for diabetes Scientific Reports |
| title | Thiosulfate sulfurtransferase prevents hyperglycemic damage to the zebrafish pronephros in an experimental model for diabetes |
| title_full | Thiosulfate sulfurtransferase prevents hyperglycemic damage to the zebrafish pronephros in an experimental model for diabetes |
| title_fullStr | Thiosulfate sulfurtransferase prevents hyperglycemic damage to the zebrafish pronephros in an experimental model for diabetes |
| title_full_unstemmed | Thiosulfate sulfurtransferase prevents hyperglycemic damage to the zebrafish pronephros in an experimental model for diabetes |
| title_short | Thiosulfate sulfurtransferase prevents hyperglycemic damage to the zebrafish pronephros in an experimental model for diabetes |
| title_sort | thiosulfate sulfurtransferase prevents hyperglycemic damage to the zebrafish pronephros in an experimental model for diabetes |
| url | https://doi.org/10.1038/s41598-022-16320-1 |
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