Thiosulfate sulfurtransferase prevents hyperglycemic damage to the zebrafish pronephros in an experimental model for diabetes.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
15 07 2022
Historique:
received: 28 02 2022
accepted: 08 07 2022
entrez: 15 7 2022
pubmed: 16 7 2022
medline: 20 7 2022
Statut: epublish

Résumé

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.

Identifiants

pubmed: 35840638
doi: 10.1038/s41598-022-16320-1
pii: 10.1038/s41598-022-16320-1
pmc: PMC9287301
doi:

Substances chimiques

Thiosulfates 0
Thiosulfate Sulfurtransferase EC 2.8.1.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

12077

Informations de copyright

© 2022. The Author(s).

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Auteurs

Zayana M Al-Dahmani (ZM)

Department of Pharmacy and Drug Design, University of Groningen, Groningen, The Netherlands.

Xiaogang Li (X)

Department of Vascular Biology and Tumor Angiogenesis, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany.

Lucas M Wiggenhauser (LM)

Department of Vascular Biology and Tumor Angiogenesis, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany.
Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, The Netherlands.

Hannes Ott (H)

Department of Vascular Biology and Tumor Angiogenesis, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany.

Paul D Kruithof (PD)

Department of Pharmacy and Drug Design, University of Groningen, Groningen, The Netherlands.

Sergey Lunev (S)

Department of Pharmacy and Drug Design, University of Groningen, Groningen, The Netherlands.

Fernando A Batista (F)

Department of Pharmacy and Drug Design, University of Groningen, Groningen, The Netherlands.

Yang Luo (Y)

Department of Pharmacy, Molecular Pharmacology, University of Groningen, Groningen, The Netherlands.

Amalia M Dolga (AM)

Department of Pharmacy, Molecular Pharmacology, University of Groningen, Groningen, The Netherlands.

Nicholas M Morton (NM)

Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.

Matthew R Groves (MR)

Department of Pharmacy and Drug Design, University of Groningen, Groningen, The Netherlands. m.r.groves@rug.nl.
XB20 Drug Design, Groningen Research Institute of Pharmacy, University of Groningen, 9700 AD, Groningen, The Netherlands. m.r.groves@rug.nl.

Jens Kroll (J)

Department of Vascular Biology and Tumor Angiogenesis, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany.

Harry van Goor (H)

Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, The Netherlands. h.van.goor@umcg.nl.
Department of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, 9700 RB, Groningen, The Netherlands. h.van.goor@umcg.nl.

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