Mannan-binding lectin deficiency augments hepatic endoplasmic reticulum stress through IP3R-controlled calcium release

Chen, Yu; Hu, Mengyao; Deng, Fan; Wang, Ping; Lin, Jingmin; Zheng, Zhuojun; Liu, Yunzhi; Dong, Lijun; Xiao, Lü; Chen, Zhengliang; Zhou, Jia; Zuo, Daming

doi:10.1016/j.ceca.2021.102477

Cited by 7 publications

(3 citation statements)

References 48 publications

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“…Therefore, we further explore whether the calcium is derived from endoplasmic reticulum. Previous studies have shown that the release of endoplasmic reticulum calcium is closely related to IP3R of ER (19). Therefore, after using IP3R-specific inhibitor (Xestospongin C: XSC, 5 µM), we found that the calcium level in mitochondria was significantly reduced (Figure 6F), indicating that calcium entered the cytoplasm from the endoplasmic reticulum, and then transfers into mitochondria.…”

Section: Microplastic Caused Vascular Cell Aging In Vitromentioning

confidence: 66%

Microplastics accelerates the premature aging of blood vessels though ROS-mediated CDK5 signaling pathway

Wang

et al. 2023

Preprint

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Background Microplastic has become a kind of pollutant widely existing in soil, atmosphere, fresh water and marine environment. At present, microplastics have been found in many tissues and organs of organisms. Research shows that as a new environmental pollutant, microplastics has shown a health hazard to human and animal. Aging and aging-related diseases are major social and medical problems facing the world. However, up to now, the effect of microplastic exposure on premature aging of blood vessels has not been evaluated. Therefore, we investigated the health damage of microplastics to blood vessels in vivo and in vitro experiments. Methods ELISA, indirect immunofluorescence, SiRNA, laser confocal microscopy, and Flow cytometry were performed to evaluate the effect of microplastics on premature aging of blood vessels. Results In vitro experiments, we found that microplastics can internalize into vascular cells, and the internalized microplastics cause damage to organelles. Further biochemical experiments showed that microplastics stimulation caused the premature aging of blood vessels by detecting a series of aging markers. Further mechanism research indicates that microplastics could increase ROS level of mitochondria mediated by calcium overload, and then ROS leads to the LaminA degradation by CDK5 mediation, further resulting in genomic instability, thus finally causing the aging of vascular cells/tissues. In vivo model, we found that microplastics induced aging damage on vascular tissue, the expression of aging maker molecules were significantly increased. Furthermore, the level of inflammation and oxidative stress was also significantly increased. Conclusion In summary, in this work, we evaluated the effect of microplastic exposure on premature aging of blood vessels, and we also revealed the molecular mechanism by which microplastics cause premature aging of the cardiovascular system.

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Section: Microplastic Caused Vascular Cell Aging In Vitromentioning

confidence: 66%

Microplastics accelerates the premature aging of blood vessels though ROS-mediated CDK5 signaling pathway

Wang

et al. 2023

Preprint

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“…Other studies have shown that ER stress-induced necroptosis in cardiac IR injury via the Ca 2+ overload pathways [ 35 ]. However, it has also been shown that IP3R-controlled Ca 2+ release could induce hepatic ER stress [ 36 ]. Also, ER Ca 2+ release potentiates the ER stress and cell death in MCF-7 cells caused by oxidative stress [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

IP3R2-mediated Ca2+ release promotes LPS-induced cardiomyocyte pyroptosis via the activation of NLRP3/Caspase-1/GSDMD pathway

Wu,

Yang,

Zhang

et al. 2024

Cell Death Discov.

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Pyroptosis plays a crucial role in sepsis, and the abnormal handling of myocyte calcium (Ca2+) has been associated with cardiomyocyte pyroptosis. Specifically, the inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is a Ca2+ release channel in the endoplasmic reticulum (ER). However, the specific role of IP3R2 in sepsis-induced cardiomyopathy (SIC) has not yet been determined. Thus, this study aimed to investigate the underlying mechanism by which IP3R2 channel-mediated Ca2+ signaling contributes to lipopolysaccharide (LPS)—induced cardiac pyroptosis. The SIC model was established in rats by intraperitoneal injection of LPS (10 mg/kg). Cardiac dysfunction was assessed using echocardiography, and the protein expression of relevant signaling pathways was analyzed using ELISA, RT-qPCR, and western blot. Small interfering RNAs (siRNA) and an inhibitor were used to explore the role of IP3R2 in neonatal rat cardiomyocytes (NRCMs) stimulated by LPS in vitro. LPS-induced NLRP3 overexpression and GSDMD-mediated pyroptosis in the rats’ heart. Treatment with the NLRP3 inhibitor MCC950 alleviated LPS-induced cardiomyocyte pyroptosis. Furthermore, LPS increased ATP-induced intracellular Ca2+ release and IP3R2 expression in NRCMs. Inhibiting IP3R activity with xestospongin C (XeC) or knocking down IP3R2 reversed LPS-induced intracellular Ca2+ release. Additionally, inhibiting IP3R2 reversed LPS-induced pyroptosis by suppressing the NLRP3/Caspase-1/GSDMD pathway. We also found that ER stress and IP3R2-mediated Ca2+ release mutually regulated each other, contributing to cardiomyocyte pyroptosis. IP3R2 promotes NLRP3-mediated pyroptosis by regulating ER Ca2+ release, and the mutual regulation of IP3R2 and ER stress further promotes LPS-induced pyroptosis in cardiomyocytes.

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“…To extract and culture mice HSCs, primary HSCs and hepatocytes were extracted from mice livers by collagenase and purified by Percoll as we previously described. 15 , 64 HSCs and hepatocytes were cultured in Dulbecco's modified Eagle medium supplemented with 10% fetal bovine serum. The activated HSCs were determined by α-SMA expression.…”

Section: Methodsmentioning

confidence: 99%

Mannan-Binding Lectin via Interaction With Cell Surface Calreticulin Promotes Senescence of Activated Hepatic Stellate Cells to Limit Liver Fibrosis Progression

Luo

Chang

et al. 2022

Cellular and Molecular Gastroenterology and Hepatology

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Mannan-binding lectin deficiency augments hepatic endoplasmic reticulum stress through IP3R-controlled calcium release

Cited by 7 publications

References 48 publications

Microplastics accelerates the premature aging of blood vessels though ROS-mediated CDK5 signaling pathway

Microplastics accelerates the premature aging of blood vessels though ROS-mediated CDK5 signaling pathway

IP3R2-mediated Ca2+ release promotes LPS-induced cardiomyocyte pyroptosis via the activation of NLRP3/Caspase-1/GSDMD pathway

Mannan-Binding Lectin via Interaction With Cell Surface Calreticulin Promotes Senescence of Activated Hepatic Stellate Cells to Limit Liver Fibrosis Progression

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