Role of 3-Mercaptopyruvate Sulfurtransferase in the Regulation of Proliferation and Cellular Bioenergetics in Human Down Syndrome Fibroblasts
Down syndrome (trisomy of human chromosome 21) is a common genetic disorder. Overproduction of the gaseous mediator hydrogen sulfide (H<sub>2</sub>S) has been implicated in the pathogenesis of neurological and metabolic deficits associated with Down syndrome. Several lines of data indica...
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| Format: | Article |
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MDPI AG
2020-04-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/4/653 |
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| author | Theodora Panagaki Elisa B. Randi Csaba Szabo |
| author_facet | Theodora Panagaki Elisa B. Randi Csaba Szabo |
| author_sort | Theodora Panagaki |
| collection | DOAJ |
| description | Down syndrome (trisomy of human chromosome 21) is a common genetic disorder. Overproduction of the gaseous mediator hydrogen sulfide (H<sub>2</sub>S) has been implicated in the pathogenesis of neurological and metabolic deficits associated with Down syndrome. Several lines of data indicate that an important enzyme responsible for H<sub>2</sub>S overproduction in Down syndrome is cystathionine-β-synthase (CBS), an enzyme localized on chromosome 21. The current study explored the possibility that a second H<sub>2</sub>S-producing enzyme, 3-mercaptopyruvate sulfurtransferase (3-MST), may also contribute to the development of functional deficits of Down syndrome cells. Western blotting analysis demonstrated a significantly higher level of 3-MST protein expression in human Down syndrome fibroblasts compared to cells from healthy control individuals; the excess 3-MST was mainly localized to the mitochondrial compartment. Pharmacological inhibition of 3-MST activity improved mitochondrial electron transport and oxidative phosphorylation parameters (but did not affect the suppressed glycolytic parameters) and enhanced cell proliferation in Down syndrome cells (but not in healthy control cells). The findings presented in the current report suggest that in addition to the indisputable role of CBS, H<sub>2</sub>S produced from 3-MST may also contribute to the development of mitochondrial metabolic and functional impairments in Down syndrome cells. |
| first_indexed | 2024-03-10T20:16:24Z |
| format | Article |
| id | doaj.art-6f7887b832884918ac9178a593ac87fb |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T20:16:24Z |
| publishDate | 2020-04-01 |
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| series | Biomolecules |
| spelling | doaj.art-6f7887b832884918ac9178a593ac87fb2023-11-19T22:31:21ZengMDPI AGBiomolecules2218-273X2020-04-0110465310.3390/biom10040653Role of 3-Mercaptopyruvate Sulfurtransferase in the Regulation of Proliferation and Cellular Bioenergetics in Human Down Syndrome FibroblastsTheodora Panagaki0Elisa B. Randi1Csaba Szabo2Chair of Pharmacology, Section of Medicine, University of Fribourg, 1700 Fribourg, SwitzerlandChair of Pharmacology, Section of Medicine, University of Fribourg, 1700 Fribourg, SwitzerlandChair of Pharmacology, Section of Medicine, University of Fribourg, 1700 Fribourg, SwitzerlandDown syndrome (trisomy of human chromosome 21) is a common genetic disorder. Overproduction of the gaseous mediator hydrogen sulfide (H<sub>2</sub>S) has been implicated in the pathogenesis of neurological and metabolic deficits associated with Down syndrome. Several lines of data indicate that an important enzyme responsible for H<sub>2</sub>S overproduction in Down syndrome is cystathionine-β-synthase (CBS), an enzyme localized on chromosome 21. The current study explored the possibility that a second H<sub>2</sub>S-producing enzyme, 3-mercaptopyruvate sulfurtransferase (3-MST), may also contribute to the development of functional deficits of Down syndrome cells. Western blotting analysis demonstrated a significantly higher level of 3-MST protein expression in human Down syndrome fibroblasts compared to cells from healthy control individuals; the excess 3-MST was mainly localized to the mitochondrial compartment. Pharmacological inhibition of 3-MST activity improved mitochondrial electron transport and oxidative phosphorylation parameters (but did not affect the suppressed glycolytic parameters) and enhanced cell proliferation in Down syndrome cells (but not in healthy control cells). The findings presented in the current report suggest that in addition to the indisputable role of CBS, H<sub>2</sub>S produced from 3-MST may also contribute to the development of mitochondrial metabolic and functional impairments in Down syndrome cells.https://www.mdpi.com/2218-273X/10/4/653trisomyhydrogen sulfidemitochondriaATP |
| spellingShingle | Theodora Panagaki Elisa B. Randi Csaba Szabo Role of 3-Mercaptopyruvate Sulfurtransferase in the Regulation of Proliferation and Cellular Bioenergetics in Human Down Syndrome Fibroblasts Biomolecules trisomy hydrogen sulfide mitochondria ATP |
| title | Role of 3-Mercaptopyruvate Sulfurtransferase in the Regulation of Proliferation and Cellular Bioenergetics in Human Down Syndrome Fibroblasts |
| title_full | Role of 3-Mercaptopyruvate Sulfurtransferase in the Regulation of Proliferation and Cellular Bioenergetics in Human Down Syndrome Fibroblasts |
| title_fullStr | Role of 3-Mercaptopyruvate Sulfurtransferase in the Regulation of Proliferation and Cellular Bioenergetics in Human Down Syndrome Fibroblasts |
| title_full_unstemmed | Role of 3-Mercaptopyruvate Sulfurtransferase in the Regulation of Proliferation and Cellular Bioenergetics in Human Down Syndrome Fibroblasts |
| title_short | Role of 3-Mercaptopyruvate Sulfurtransferase in the Regulation of Proliferation and Cellular Bioenergetics in Human Down Syndrome Fibroblasts |
| title_sort | role of 3 mercaptopyruvate sulfurtransferase in the regulation of proliferation and cellular bioenergetics in human down syndrome fibroblasts |
| topic | trisomy hydrogen sulfide mitochondria ATP |
| url | https://www.mdpi.com/2218-273X/10/4/653 |
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