Pathophysiological Concepts in Multiple Sclerosis and the Therapeutic Effects of Hydrogen Sulfide
Introduction: Multiple sclerosis (MS) is generally known as a manageable but not yet curable autoimmune disease affecting central nervous system. A potential therapeutic approach should possess several properties: Prevent immune system from damaging the brain and spinal cord,&n...
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| Format: | Article |
| Language: | English |
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Iran University of Medical Sciences
2016-04-01
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| Series: | Basic and Clinical Neuroscience |
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| Online Access: | http://bcn.iums.ac.ir/browse.php?a_code=A-10-782-1&slc_lang=en&sid=1 |
| _version_ | 1827334507361992704 |
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| author | Fatemeh Talaei |
| author_facet | Fatemeh Talaei |
| author_sort | Fatemeh Talaei |
| collection | DOAJ |
| description | Introduction: Multiple sclerosis (MS) is generally known as a manageable but not yet curable autoimmune disease affecting central nervous system. A potential therapeutic approach should possess several properties: Prevent immune system from damaging the brain and spinal cord, promote differentiation of oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes to produce myelin, prevent the formation of fibronectin aggregates by astrocytes to inhibit scar formation, and enhance function of healthy endothelial cells (ECs).
Methods: To determine if an increase in sulfur contents through H2S, a potent antioxidant known to induce protective autophagy in cells, could provide the above desired outcomes, peripheral blood mononuclear cells (PBMNCs), OCPs, astrocytes, and ECs were treated with NaHS (50 μM) in vitro.
Results: Transmigration assay using EC monolayer showed that serotonin increased migration of PBMNC while pretreatment of EC with NaHS inhibited the migration induced by serotonin treatment. NaHS upregulated proteins involved in immune system response and downregulated PBMNCs- and EC-related adhesion molecules (LFA-1 and VCAM-1). Furthermore, it had a cell expansion inducing effect, altering EC morphology. The effects of NaHS on OPCs and astrocytes were studied compared to mTOR inhibitor rapamycin. In NaHS treated astrocytes the induced fibronectin production was partially inhibited while rapamycin almost fully inhibited fibronectin production. NaHS slowed but did not inhibit the differentiation of OCPs or the production of myelin compared to rapamycin.
Conclusion: The in vitro results point to the potential therapeutic application of hydrogen sulfide releasing molecules or health-promoting sulfur compounds in MS. |
| first_indexed | 2024-03-07T17:55:39Z |
| format | Article |
| id | doaj.art-3ba7f9ca76d9474589d2dfd16f51cd41 |
| institution | Directory Open Access Journal |
| issn | 2008-126X 2228-7442 |
| language | English |
| last_indexed | 2024-03-07T17:55:39Z |
| publishDate | 2016-04-01 |
| publisher | Iran University of Medical Sciences |
| record_format | Article |
| series | Basic and Clinical Neuroscience |
| spelling | doaj.art-3ba7f9ca76d9474589d2dfd16f51cd412024-03-02T12:15:54ZengIran University of Medical SciencesBasic and Clinical Neuroscience2008-126X2228-74422016-04-0172121136Pathophysiological Concepts in Multiple Sclerosis and the Therapeutic Effects of Hydrogen SulfideFatemeh Talaei0 Novel Drug Delivery Systems Lab, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Introduction: Multiple sclerosis (MS) is generally known as a manageable but not yet curable autoimmune disease affecting central nervous system. A potential therapeutic approach should possess several properties: Prevent immune system from damaging the brain and spinal cord, promote differentiation of oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes to produce myelin, prevent the formation of fibronectin aggregates by astrocytes to inhibit scar formation, and enhance function of healthy endothelial cells (ECs). Methods: To determine if an increase in sulfur contents through H2S, a potent antioxidant known to induce protective autophagy in cells, could provide the above desired outcomes, peripheral blood mononuclear cells (PBMNCs), OCPs, astrocytes, and ECs were treated with NaHS (50 μM) in vitro. Results: Transmigration assay using EC monolayer showed that serotonin increased migration of PBMNC while pretreatment of EC with NaHS inhibited the migration induced by serotonin treatment. NaHS upregulated proteins involved in immune system response and downregulated PBMNCs- and EC-related adhesion molecules (LFA-1 and VCAM-1). Furthermore, it had a cell expansion inducing effect, altering EC morphology. The effects of NaHS on OPCs and astrocytes were studied compared to mTOR inhibitor rapamycin. In NaHS treated astrocytes the induced fibronectin production was partially inhibited while rapamycin almost fully inhibited fibronectin production. NaHS slowed but did not inhibit the differentiation of OCPs or the production of myelin compared to rapamycin. Conclusion: The in vitro results point to the potential therapeutic application of hydrogen sulfide releasing molecules or health-promoting sulfur compounds in MS.http://bcn.iums.ac.ir/browse.php?a_code=A-10-782-1&slc_lang=en&sid=1NaHS Fibronectin Myelin Astrocytes Oligodendrocytes HUVEC Peripheral Blood Mononuclear Cells |
| spellingShingle | Fatemeh Talaei Pathophysiological Concepts in Multiple Sclerosis and the Therapeutic Effects of Hydrogen Sulfide Basic and Clinical Neuroscience NaHS Fibronectin Myelin Astrocytes Oligodendrocytes HUVEC Peripheral Blood Mononuclear Cells |
| title | Pathophysiological Concepts in Multiple Sclerosis and the Therapeutic Effects of Hydrogen Sulfide |
| title_full | Pathophysiological Concepts in Multiple Sclerosis and the Therapeutic Effects of Hydrogen Sulfide |
| title_fullStr | Pathophysiological Concepts in Multiple Sclerosis and the Therapeutic Effects of Hydrogen Sulfide |
| title_full_unstemmed | Pathophysiological Concepts in Multiple Sclerosis and the Therapeutic Effects of Hydrogen Sulfide |
| title_short | Pathophysiological Concepts in Multiple Sclerosis and the Therapeutic Effects of Hydrogen Sulfide |
| title_sort | pathophysiological concepts in multiple sclerosis and the therapeutic effects of hydrogen sulfide |
| topic | NaHS Fibronectin Myelin Astrocytes Oligodendrocytes HUVEC Peripheral Blood Mononuclear Cells |
| url | http://bcn.iums.ac.ir/browse.php?a_code=A-10-782-1&slc_lang=en&sid=1 |
| work_keys_str_mv | AT fatemehtalaei pathophysiologicalconceptsinmultiplesclerosisandthetherapeuticeffectsofhydrogensulfide |