Patulin induces ROS-dependent cardiac cell toxicity by inducing DNA damage and activating endoplasmic reticulum stress apoptotic pathway
Patulin (PAT) is one of the mycotoxins commonly found in agricultural products and fruits, and has obvious toxic effects on animals and humans. PAT has been found to cause myocardial toxicity and oxidative damage, but the mechanism of myocardial toxicity remained to be elucidated. We investigated th...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651323012885 |
| _version_ | 1797401851530838016 |
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| author | Baigang Zhang Chenghui Huang Dongmei Xu Ke Huang Yang Li Lu Jiao Binggang Fu Subing Li Yi Li |
| author_facet | Baigang Zhang Chenghui Huang Dongmei Xu Ke Huang Yang Li Lu Jiao Binggang Fu Subing Li Yi Li |
| author_sort | Baigang Zhang |
| collection | DOAJ |
| description | Patulin (PAT) is one of the mycotoxins commonly found in agricultural products and fruits, and has obvious toxic effects on animals and humans. PAT has been found to cause myocardial toxicity and oxidative damage, but the mechanism of myocardial toxicity remained to be elucidated. We investigated the toxic effects and potential mechanisms of PAT on human cardiomyocytes and explored the effects of reactive oxygen species (ROS) on them. The study showed that treatment with PAT for 24 h decreased cell viability and superoxide dismutase (SOD) activity, and increased ROS and lactate dehydrogenase (LDH) levels. Moreover, in addition to detecting increased γ-H2AX expression and observing nuclear damage, the comet assay also showed increased DNA tail distance in the PAT-treated group, followed by an increase in phosphorylation of the p53 protein and p21 protein expression, and a decrease in CDK1 and Cyclin B1 protein expression, and G2/M phase arrest. In addition, PAT induced endoplasmic reticulum stress (ERS) and induced apoptosis, as evidenced by Ca2+ increase, ER enlargement and swelling, and upregulation of ERS-related genes and proteins expression, and increased expression of three apoptotic pathway proteins under ERS, including CHOP, JNK, and caspase-12. Meanwhile, N-acetylcysteine (NAC, a ROS scavenger) reversed the negative effects of PAT treatment on cells. These results clarify that excessive ROS production by PAT-treated AC16 cells not only causes DNA damage, leading to cell cycle arrest, but also causes ERS, which triggers apoptotic pathways to cause apoptosis. |
| first_indexed | 2024-03-09T02:16:17Z |
| format | Article |
| id | doaj.art-df84ed1c65614949bd8157919bfb4490 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-03-09T02:16:17Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-df84ed1c65614949bd8157919bfb44902023-12-07T05:27:29ZengElsevierEcotoxicology and Environmental Safety0147-65132024-01-01269115784Patulin induces ROS-dependent cardiac cell toxicity by inducing DNA damage and activating endoplasmic reticulum stress apoptotic pathwayBaigang Zhang0Chenghui Huang1Dongmei Xu2Ke Huang3Yang Li4Lu Jiao5Binggang Fu6Subing Li7Yi Li8Life Science and Engineering, Lanzhou University of Technology, Lanzhou, Gansu 730050, ChinaLife Science and Engineering, Lanzhou University of Technology, Lanzhou, Gansu 730050, ChinaLife Science and Engineering, Lanzhou University of Technology, Lanzhou, Gansu 730050, ChinaKey Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Dental Maxillofacial Reconstruction and Biological Intelligence Manufacturing, School of Stomatology, Lanzhou University, Lanzhou 730030, ChinaLife Science and Engineering, Lanzhou University of Technology, Lanzhou, Gansu 730050, ChinaLife Science and Engineering, Lanzhou University of Technology, Lanzhou, Gansu 730050, ChinaLife Science and Engineering, Lanzhou University of Technology, Lanzhou, Gansu 730050, ChinaLife Science and Engineering, Lanzhou University of Technology, Lanzhou, Gansu 730050, ChinaKey Laboratory of Dental Maxillofacial Reconstruction and Biological Intelligence Manufacturing, School of Stomatology, Lanzhou University, Lanzhou 730030, China; Corresponding author.Patulin (PAT) is one of the mycotoxins commonly found in agricultural products and fruits, and has obvious toxic effects on animals and humans. PAT has been found to cause myocardial toxicity and oxidative damage, but the mechanism of myocardial toxicity remained to be elucidated. We investigated the toxic effects and potential mechanisms of PAT on human cardiomyocytes and explored the effects of reactive oxygen species (ROS) on them. The study showed that treatment with PAT for 24 h decreased cell viability and superoxide dismutase (SOD) activity, and increased ROS and lactate dehydrogenase (LDH) levels. Moreover, in addition to detecting increased γ-H2AX expression and observing nuclear damage, the comet assay also showed increased DNA tail distance in the PAT-treated group, followed by an increase in phosphorylation of the p53 protein and p21 protein expression, and a decrease in CDK1 and Cyclin B1 protein expression, and G2/M phase arrest. In addition, PAT induced endoplasmic reticulum stress (ERS) and induced apoptosis, as evidenced by Ca2+ increase, ER enlargement and swelling, and upregulation of ERS-related genes and proteins expression, and increased expression of three apoptotic pathway proteins under ERS, including CHOP, JNK, and caspase-12. Meanwhile, N-acetylcysteine (NAC, a ROS scavenger) reversed the negative effects of PAT treatment on cells. These results clarify that excessive ROS production by PAT-treated AC16 cells not only causes DNA damage, leading to cell cycle arrest, but also causes ERS, which triggers apoptotic pathways to cause apoptosis.http://www.sciencedirect.com/science/article/pii/S0147651323012885PatulinCycle arrestDNA damageEndoplasmic reticulum stressApoptosis |
| spellingShingle | Baigang Zhang Chenghui Huang Dongmei Xu Ke Huang Yang Li Lu Jiao Binggang Fu Subing Li Yi Li Patulin induces ROS-dependent cardiac cell toxicity by inducing DNA damage and activating endoplasmic reticulum stress apoptotic pathway Ecotoxicology and Environmental Safety Patulin Cycle arrest DNA damage Endoplasmic reticulum stress Apoptosis |
| title | Patulin induces ROS-dependent cardiac cell toxicity by inducing DNA damage and activating endoplasmic reticulum stress apoptotic pathway |
| title_full | Patulin induces ROS-dependent cardiac cell toxicity by inducing DNA damage and activating endoplasmic reticulum stress apoptotic pathway |
| title_fullStr | Patulin induces ROS-dependent cardiac cell toxicity by inducing DNA damage and activating endoplasmic reticulum stress apoptotic pathway |
| title_full_unstemmed | Patulin induces ROS-dependent cardiac cell toxicity by inducing DNA damage and activating endoplasmic reticulum stress apoptotic pathway |
| title_short | Patulin induces ROS-dependent cardiac cell toxicity by inducing DNA damage and activating endoplasmic reticulum stress apoptotic pathway |
| title_sort | patulin induces ros dependent cardiac cell toxicity by inducing dna damage and activating endoplasmic reticulum stress apoptotic pathway |
| topic | Patulin Cycle arrest DNA damage Endoplasmic reticulum stress Apoptosis |
| url | http://www.sciencedirect.com/science/article/pii/S0147651323012885 |
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