Itaconic Acid as A Differential Transcription Regulator of Apoptosis and Autophagy Pathways Genes: A Rat Adipose Mesenchymal Stem Cells Model
Objective: Itaconate, a novel regulatory immunometabolite, is synthesized by inflammatory macrophage. It acts as an anti-inflammatory mediator and regulates several metabolic and signaling pathways particularly Nrf2 pathway. The immunometabolites can affect the stemness potency, differentiation abil...
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| Format: | Article |
| Language: | English |
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Royan Institute (ACECR), Tehran
2022-10-01
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| Series: | Cell Journal |
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| Online Access: | https://www.celljournal.org/article_253354_2369075124c30da638b9f966909fc86c.pdf |
| _version_ | 1828104014910193664 |
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| author | Mohammad Reza Tabandeh fatemeh soroush dian dayer |
| author_facet | Mohammad Reza Tabandeh fatemeh soroush dian dayer |
| author_sort | Mohammad Reza Tabandeh |
| collection | DOAJ |
| description | Objective: Itaconate, a novel regulatory immunometabolite, is synthesized by inflammatory macrophage. It acts as an anti-inflammatory mediator and regulates several metabolic and signaling pathways particularly Nrf2 pathway. The immunometabolites can affect the stemness potency, differentiation ability and viability of stem cells, but little is known about the critical function of Itaconate on the stem cell fate. The objective of the present study was to determine the regulatory effects of Itaconic acid on the cell viability and transcription of apoptosis and autophagy pathways genes in the rat adipose derived mesenchymal stem cells (ADMSCs).Materials and Methods: In this experimental study, the ADMSCs were incubated with 125 μM and 250 μM dimethylitaconate (DMI) for 24 hours or 48 hours. The expression of apoptosis pathway genes (Bax, Bcl2, Caspase 3, Fas, Fadd and Caspase 8) and autophagy pathway genes (Atg12, Atg5, Beclin, Lc3b and P62) were determined using real time polymerase chain reaction (PCR) assay. Using the ELISA method, cellular level of phospho-NRF2 protein was measured.Results: The results indicated that DMI increased the expression of NRF2 protein, altered the expression of someapoptosis genes (Fadd, Bax and Bcl2), and changed the expression of some autophagy related genes (Lc3b, Becline and P62) in ADMSCs. DMI had no obvious effect on the transcription of caspases enzymes.Conclusion: Because autophagy activation and apoptosis suppression can protect stem cells against environmental stress, it seems Itaconate can affect the functions and viability of ADMSCs via converse regulation of these pathways. |
| first_indexed | 2024-04-11T09:35:47Z |
| format | Article |
| id | doaj.art-83872ce47e22415c84e50265b1c65084 |
| institution | Directory Open Access Journal |
| issn | 2228-5806 2228-5814 |
| language | English |
| last_indexed | 2024-04-11T09:35:47Z |
| publishDate | 2022-10-01 |
| publisher | Royan Institute (ACECR), Tehran |
| record_format | Article |
| series | Cell Journal |
| spelling | doaj.art-83872ce47e22415c84e50265b1c650842022-12-22T04:31:44ZengRoyan Institute (ACECR), TehranCell Journal2228-58062228-58142022-10-01241058659510.22074/cellj.2022.8320253354Itaconic Acid as A Differential Transcription Regulator of Apoptosis and Autophagy Pathways Genes: A Rat Adipose Mesenchymal Stem Cells ModelMohammad Reza Tabandeh0fatemeh soroush1dian dayer2Department of Basic Sciences, Division of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, IranDepartment of Basic Sciences, Division of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, IranCellular and Molecular Research Center, Medical Basic Sciences Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranObjective: Itaconate, a novel regulatory immunometabolite, is synthesized by inflammatory macrophage. It acts as an anti-inflammatory mediator and regulates several metabolic and signaling pathways particularly Nrf2 pathway. The immunometabolites can affect the stemness potency, differentiation ability and viability of stem cells, but little is known about the critical function of Itaconate on the stem cell fate. The objective of the present study was to determine the regulatory effects of Itaconic acid on the cell viability and transcription of apoptosis and autophagy pathways genes in the rat adipose derived mesenchymal stem cells (ADMSCs).Materials and Methods: In this experimental study, the ADMSCs were incubated with 125 μM and 250 μM dimethylitaconate (DMI) for 24 hours or 48 hours. The expression of apoptosis pathway genes (Bax, Bcl2, Caspase 3, Fas, Fadd and Caspase 8) and autophagy pathway genes (Atg12, Atg5, Beclin, Lc3b and P62) were determined using real time polymerase chain reaction (PCR) assay. Using the ELISA method, cellular level of phospho-NRF2 protein was measured.Results: The results indicated that DMI increased the expression of NRF2 protein, altered the expression of someapoptosis genes (Fadd, Bax and Bcl2), and changed the expression of some autophagy related genes (Lc3b, Becline and P62) in ADMSCs. DMI had no obvious effect on the transcription of caspases enzymes.Conclusion: Because autophagy activation and apoptosis suppression can protect stem cells against environmental stress, it seems Itaconate can affect the functions and viability of ADMSCs via converse regulation of these pathways.https://www.celljournal.org/article_253354_2369075124c30da638b9f966909fc86c.pdfadipose derived mesenchymal stem cellsitaconateautophagyapoptosis |
| spellingShingle | Mohammad Reza Tabandeh fatemeh soroush dian dayer Itaconic Acid as A Differential Transcription Regulator of Apoptosis and Autophagy Pathways Genes: A Rat Adipose Mesenchymal Stem Cells Model Cell Journal adipose derived mesenchymal stem cells itaconate autophagy apoptosis |
| title | Itaconic Acid as A Differential Transcription Regulator of Apoptosis and Autophagy Pathways Genes: A Rat Adipose Mesenchymal Stem Cells Model |
| title_full | Itaconic Acid as A Differential Transcription Regulator of Apoptosis and Autophagy Pathways Genes: A Rat Adipose Mesenchymal Stem Cells Model |
| title_fullStr | Itaconic Acid as A Differential Transcription Regulator of Apoptosis and Autophagy Pathways Genes: A Rat Adipose Mesenchymal Stem Cells Model |
| title_full_unstemmed | Itaconic Acid as A Differential Transcription Regulator of Apoptosis and Autophagy Pathways Genes: A Rat Adipose Mesenchymal Stem Cells Model |
| title_short | Itaconic Acid as A Differential Transcription Regulator of Apoptosis and Autophagy Pathways Genes: A Rat Adipose Mesenchymal Stem Cells Model |
| title_sort | itaconic acid as a differential transcription regulator of apoptosis and autophagy pathways genes a rat adipose mesenchymal stem cells model |
| topic | adipose derived mesenchymal stem cells itaconate autophagy apoptosis |
| url | https://www.celljournal.org/article_253354_2369075124c30da638b9f966909fc86c.pdf |
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