The phosphorylation of Smad3 by CaMKIIγ leads to the hepatocyte pyroptosis under perfluorooctane sulfonate exposure
Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant and accumulated in the liver of mammals. PFOS exposure is closely associated with the development of pyroptosis. Nevertheless, the underlying mechanism is unclear. We found here that PFOS induced pyroptosis in the mice liver and L-02...
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Elsevier
2024-10-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324010005 |
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| author | Siyu Ren Peiyao Liang Ruzhen Feng Wei Yang Tianming Qiu Jingyuan Zhang Qiujuan Li Guang Yang Xiance Sun Xiaofeng Yao |
| author_facet | Siyu Ren Peiyao Liang Ruzhen Feng Wei Yang Tianming Qiu Jingyuan Zhang Qiujuan Li Guang Yang Xiance Sun Xiaofeng Yao |
| author_sort | Siyu Ren |
| collection | DOAJ |
| description | Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant and accumulated in the liver of mammals. PFOS exposure is closely associated with the development of pyroptosis. Nevertheless, the underlying mechanism is unclear. We found here that PFOS induced pyroptosis in the mice liver and L-02 cells as demonstrated by activation of the NOD-like receptor protein 3 inflammasome, gasdermin D cleavage and increased release of interleukin-1β and interleukin-18. The level of cytoplasmic calcium was accelerated in hepatocytes upon exposure to PFOS. The phosphorylated/activated form of calcium/calmodulin-dependent protein kinase II (CaMKII) was augmented by PFOS in vivo and in vitro. PFOS-induced pyroptosis was relieved by CaMKII inhibitor. Among various CaMKII subtypes, we identified that CaMKIIγ was activated specifically by PFOS. CaMKIIγ interacted with Smad family member 3 (Smad3) under PFOS exposure. PFOS increased the phosphorylation of Smad3, and CaMKII inhibitor or CaMKIIγ siRNA alleviated PFOS-caused phosphorylation of Smad3. Inhibiting Smad3 activity was found to alleviate PFOS-induced hepatocyte pyroptosis. This study puts forward that CaMKIIγ-Smad3 is the linkage between calcium homeostasis disturbance and pyroptosis, providing a mechanistic explanation for PFOS-induced pyroptosis. |
| format | Article |
| id | doaj-art-6beb476e515d46ad9be020f718fd2f02 |
| institution | OA Journals |
| issn | 0147-6513 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-6beb476e515d46ad9be020f718fd2f022025-08-20T01:54:44ZengElsevierEcotoxicology and Environmental Safety0147-65132024-10-0128411692410.1016/j.ecoenv.2024.116924The phosphorylation of Smad3 by CaMKIIγ leads to the hepatocyte pyroptosis under perfluorooctane sulfonate exposureSiyu Ren0Peiyao Liang1Ruzhen Feng2Wei Yang3Tianming Qiu4Jingyuan Zhang5Qiujuan Li6Guang Yang7Xiance Sun8Xiaofeng Yao9Department of Occupation and Environment Health, Dalian Medical University, 9 Lvshun South Road, Dalian, ChinaDepartment of Occupation and Environment Health, Dalian Medical University, 9 Lvshun South Road, Dalian, ChinaDepartment of Occupation and Environment Health, Dalian Medical University, 9 Lvshun South Road, Dalian, ChinaDepartment of Occupation and Environment Health, Dalian Medical University, 9 Lvshun South Road, Dalian, ChinaDepartment of Occupation and Environment Health, Dalian Medical University, 9 Lvshun South Road, Dalian, China; Corresponding authors.Department of Occupation and Environment Health, Dalian Medical University, 9 Lvshun South Road, Dalian, ChinaDepartment of Nutrition, Dalian Medical University, 9 Lvshun South Road, Dalian, ChinaDepartment of Nutrition, Dalian Medical University, 9 Lvshun South Road, Dalian, ChinaDepartment of Occupation and Environment Health, Dalian Medical University, 9 Lvshun South Road, Dalian, ChinaDepartment of Occupation and Environment Health, Dalian Medical University, 9 Lvshun South Road, Dalian, China; Corresponding authors.Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant and accumulated in the liver of mammals. PFOS exposure is closely associated with the development of pyroptosis. Nevertheless, the underlying mechanism is unclear. We found here that PFOS induced pyroptosis in the mice liver and L-02 cells as demonstrated by activation of the NOD-like receptor protein 3 inflammasome, gasdermin D cleavage and increased release of interleukin-1β and interleukin-18. The level of cytoplasmic calcium was accelerated in hepatocytes upon exposure to PFOS. The phosphorylated/activated form of calcium/calmodulin-dependent protein kinase II (CaMKII) was augmented by PFOS in vivo and in vitro. PFOS-induced pyroptosis was relieved by CaMKII inhibitor. Among various CaMKII subtypes, we identified that CaMKIIγ was activated specifically by PFOS. CaMKIIγ interacted with Smad family member 3 (Smad3) under PFOS exposure. PFOS increased the phosphorylation of Smad3, and CaMKII inhibitor or CaMKIIγ siRNA alleviated PFOS-caused phosphorylation of Smad3. Inhibiting Smad3 activity was found to alleviate PFOS-induced hepatocyte pyroptosis. This study puts forward that CaMKIIγ-Smad3 is the linkage between calcium homeostasis disturbance and pyroptosis, providing a mechanistic explanation for PFOS-induced pyroptosis.http://www.sciencedirect.com/science/article/pii/S0147651324010005Perfluorooctane sulfonatePyroptosisCytoplasmic calciumCalcium/calmodulin-dependent protein kinase II γSmad family member 3 |
| spellingShingle | Siyu Ren Peiyao Liang Ruzhen Feng Wei Yang Tianming Qiu Jingyuan Zhang Qiujuan Li Guang Yang Xiance Sun Xiaofeng Yao The phosphorylation of Smad3 by CaMKIIγ leads to the hepatocyte pyroptosis under perfluorooctane sulfonate exposure Ecotoxicology and Environmental Safety Perfluorooctane sulfonate Pyroptosis Cytoplasmic calcium Calcium/calmodulin-dependent protein kinase II γ Smad family member 3 |
| title | The phosphorylation of Smad3 by CaMKIIγ leads to the hepatocyte pyroptosis under perfluorooctane sulfonate exposure |
| title_full | The phosphorylation of Smad3 by CaMKIIγ leads to the hepatocyte pyroptosis under perfluorooctane sulfonate exposure |
| title_fullStr | The phosphorylation of Smad3 by CaMKIIγ leads to the hepatocyte pyroptosis under perfluorooctane sulfonate exposure |
| title_full_unstemmed | The phosphorylation of Smad3 by CaMKIIγ leads to the hepatocyte pyroptosis under perfluorooctane sulfonate exposure |
| title_short | The phosphorylation of Smad3 by CaMKIIγ leads to the hepatocyte pyroptosis under perfluorooctane sulfonate exposure |
| title_sort | phosphorylation of smad3 by camkiiγ leads to the hepatocyte pyroptosis under perfluorooctane sulfonate exposure |
| topic | Perfluorooctane sulfonate Pyroptosis Cytoplasmic calcium Calcium/calmodulin-dependent protein kinase II γ Smad family member 3 |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324010005 |
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