Plant Polyphenol Gossypol Induced Cell Death and Its Association with Gene Expression in Mouse Macrophages
Gossypol is a complex plant polyphenol reported to be cytotoxic and anti-inflammatory, but little is known about its effect on gene expression in macrophages. The objective of this study was to explore gossypol’s toxicity and its effect on gene expression involved in the inflammatory response, gluco...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-03-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/13/4/624 |
| _version_ | 1797606220074319872 |
|---|---|
| author | Heping Cao Kandan Sethumadhavan |
| author_facet | Heping Cao Kandan Sethumadhavan |
| author_sort | Heping Cao |
| collection | DOAJ |
| description | Gossypol is a complex plant polyphenol reported to be cytotoxic and anti-inflammatory, but little is known about its effect on gene expression in macrophages. The objective of this study was to explore gossypol’s toxicity and its effect on gene expression involved in the inflammatory response, glucose transport and insulin signaling pathways in mouse macrophages. Mouse RAW264.7 macrophages were treated with multiple concentrations of gossypol for 2–24 h. Gossypol toxicity was estimated by MTT assay and soluble protein content. qPCR analyzed the expression of anti-inflammatory tristetraprolin family (TTP/ZFP36), proinflammatory cytokine, glucose transporter (GLUT) and insulin signaling genes. Cell viability was greatly reduced by gossypol, accompanied with a dramatic reduction in soluble protein content in the cells. Gossypol treatment resulted in an increase in TTP mRNA level by 6–20-fold and increased ZFP36L1, ZFP36L2 and ZFP36L3 mRNA levels by 26–69-fold. Gossypol increased proinflammatory cytokine TNF, COX2, GM-CSF, INFγ and IL12b mRNA levels up to 39–458-fold. Gossypol treatment upregulated mRNA levels of GLUT1, GLUT3 and GLUT4 genes as well as INSR, AKT1, PIK3R1 and LEPR, but not APP genes. This study demonstrated that gossypol induced macrophage death and reduced soluble protein content, which was accompanied with the massive stimulation of anti-inflammatory TTP family and proinflammatory cytokine gene expression, as well as the elevation of gene expression involved in glucose transport and the insulin signaling pathway in mouse macrophages. |
| first_indexed | 2024-03-11T05:12:05Z |
| format | Article |
| id | doaj.art-8183825b4e93478bb04125f2190e590e |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T05:12:05Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-8183825b4e93478bb04125f2190e590e2023-11-17T18:29:04ZengMDPI AGBiomolecules2218-273X2023-03-0113462410.3390/biom13040624Plant Polyphenol Gossypol Induced Cell Death and Its Association with Gene Expression in Mouse MacrophagesHeping Cao0Kandan Sethumadhavan1United States Department of Agriculture, Agricultural Research Service, Southern Regional Research Center, New Orleans, LA 70124, USAUnited States Department of Agriculture, Agricultural Research Service, Southern Regional Research Center, New Orleans, LA 70124, USAGossypol is a complex plant polyphenol reported to be cytotoxic and anti-inflammatory, but little is known about its effect on gene expression in macrophages. The objective of this study was to explore gossypol’s toxicity and its effect on gene expression involved in the inflammatory response, glucose transport and insulin signaling pathways in mouse macrophages. Mouse RAW264.7 macrophages were treated with multiple concentrations of gossypol for 2–24 h. Gossypol toxicity was estimated by MTT assay and soluble protein content. qPCR analyzed the expression of anti-inflammatory tristetraprolin family (TTP/ZFP36), proinflammatory cytokine, glucose transporter (GLUT) and insulin signaling genes. Cell viability was greatly reduced by gossypol, accompanied with a dramatic reduction in soluble protein content in the cells. Gossypol treatment resulted in an increase in TTP mRNA level by 6–20-fold and increased ZFP36L1, ZFP36L2 and ZFP36L3 mRNA levels by 26–69-fold. Gossypol increased proinflammatory cytokine TNF, COX2, GM-CSF, INFγ and IL12b mRNA levels up to 39–458-fold. Gossypol treatment upregulated mRNA levels of GLUT1, GLUT3 and GLUT4 genes as well as INSR, AKT1, PIK3R1 and LEPR, but not APP genes. This study demonstrated that gossypol induced macrophage death and reduced soluble protein content, which was accompanied with the massive stimulation of anti-inflammatory TTP family and proinflammatory cytokine gene expression, as well as the elevation of gene expression involved in glucose transport and the insulin signaling pathway in mouse macrophages.https://www.mdpi.com/2218-273X/13/4/624cytokinegene expressionglucose transportgossypolinflammationinsulin signaling |
| spellingShingle | Heping Cao Kandan Sethumadhavan Plant Polyphenol Gossypol Induced Cell Death and Its Association with Gene Expression in Mouse Macrophages Biomolecules cytokine gene expression glucose transport gossypol inflammation insulin signaling |
| title | Plant Polyphenol Gossypol Induced Cell Death and Its Association with Gene Expression in Mouse Macrophages |
| title_full | Plant Polyphenol Gossypol Induced Cell Death and Its Association with Gene Expression in Mouse Macrophages |
| title_fullStr | Plant Polyphenol Gossypol Induced Cell Death and Its Association with Gene Expression in Mouse Macrophages |
| title_full_unstemmed | Plant Polyphenol Gossypol Induced Cell Death and Its Association with Gene Expression in Mouse Macrophages |
| title_short | Plant Polyphenol Gossypol Induced Cell Death and Its Association with Gene Expression in Mouse Macrophages |
| title_sort | plant polyphenol gossypol induced cell death and its association with gene expression in mouse macrophages |
| topic | cytokine gene expression glucose transport gossypol inflammation insulin signaling |
| url | https://www.mdpi.com/2218-273X/13/4/624 |
| work_keys_str_mv | AT hepingcao plantpolyphenolgossypolinducedcelldeathanditsassociationwithgeneexpressioninmousemacrophages AT kandansethumadhavan plantpolyphenolgossypolinducedcelldeathanditsassociationwithgeneexpressioninmousemacrophages |