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The immunity-related GTPase Irgm3 relieves endoplasmic reticulum stress response during coxsackievirus B3 infection via a PI3K/Akt dependent pathway.

ABSTRACT: The IRG protein Irgm3 preserves cell survival during coxsackievirus B3 (CVB3) infection. However, the molecular mechanisms are not clear. Here, we examined the effect of Irgm3 expression on ER stress triggered by pharmacological agents or CVB3 infection. In Tet-On/Irgm3 HeLa cells, Irgm3 expression suppressed either chemical- or CVB3-induced upregulation of glucose-regulated protein 78. Further, Irgm3 strongly inhibited the activation of both the PERK and ATF6 pathways of ER stress responses, which further led to the diminished phosphorylation of eIF2?, reduced cleavage/activation of transcription factor SREBP1 and attenuated induction of proapoptotic genes CHOP and GADD34. These data were further supported by experiments using Irgm3 knockout mouse embryonic fibroblasts, in which the ER stress induced by CVB3 was not relieved due to the lack of Irgm3 expression. In addition, the tunicamycin-triggered ER stress promoted the subsequent CVB3 infection. The effect of Irgm3 on ER stress and CVB3 infection was diminished by the PI3K inhibitor, LY294002, while inhibitors of ERK, JNK and p38 had no effect. These data were further corroborated by transfection of cells with a dominant negative Akt. Taken together, these data suggest that Irgm3 relieves the ER stress response via a PI3K/Akt dependent mechanism, which contributes to host defence against CVB3 infection.

SUBMITTER: Liu Z

PROVIDER: S-EPMC3691006 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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The immunity-related GTPase Irgm3 relieves endoplasmic reticulum stress response during coxsackievirus B3 infection via a PI3K/Akt dependent pathway.

Liu Zhen Z Zhang Huifang M HM Yuan Ji J Ye Xin X Taylor Gregory A GA Yang Decheng D

Cellular microbiology 20111110 1

The IRG protein Irgm3 preserves cell survival during coxsackievirus B3 (CVB3) infection. However, the molecular mechanisms are not clear. Here, we examined the effect of Irgm3 expression on ER stress triggered by pharmacological agents or CVB3 infection. In Tet-On/Irgm3 HeLa cells, Irgm3 expression suppressed either chemical- or CVB3-induced upregulation of glucose-regulated protein 78. Further, Irgm3 strongly inhibited the activation of both the PERK and ATF6 pathways of ER stress responses, wh ...[more]

PMID: 21981022

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Project description:Background:Diabetic cardiomyopathy (DCM), which is associated with many pathological processes, commonly occurs when advanced glycation end products (AGEs) are present. ?-carotene (BC) is a well-known vitamin A precursor that is found in many fruits and vegetables. BC can reduce the risk of cancer and cardiovascular disease. This study aimed to investigate the effect of BC on AGE-induced myocardial injury in vitro. Methods:Cell viability test was used to select 40 µM concentrations of BC to treat AGE-induced H2c9 cells. The cell apoptosis was detected by flow cytometry. Western blotting was used to measure the protein expression levels of Bcl-2-associated X protein (Bax), B-cell lymphoma-2 (Bcl-2), cleaved caspase-3, activating transcription factor 4 (ATF4), glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), beclin 1, p62,microtubule-associated protein 1 light chain 3 (LC3), phosphorylated PI3K (p-PI3K), phosphorylated Akt (p-AKT), and phosphorylated mTOR (p-mTOR). Enzyme-linked immunosorbent assay (ELISA) was performed to measure the levels of lactate dehydrogenase (LDH) and cardiac troponin-1 (cTn-I). Reactive oxygen species (ROS) was detected by flow cytometry. The levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) were used to determine MDA kits, SOD assay kit and GSH-Px kit, respectively. Results:BC significantly inhibited AGE-induced cell death and apoptosis in H9c2 cells. BC had a suppressive effect on intracellular ROS production and antioxidative enzyme reduction. Moreover, BC decreased hyperactive endoplasmic reticulum (ER) stress and autophagy in H9c2 cells. Furthermore, BC exerted a cardioprotective effect in AGE-induced H9c2 cells via the activation of the PI3K/Akt/mTOR signaling pathway. Conclusions:BC exhibited a cardioprotective effect AGE-induced apoptosis. Our study provides a foundation for further study into the potential value of BC for treating DCM or other heart diseases.

Dataset Information

The immunity-related GTPase Irgm3 relieves endoplasmic reticulum stress response during coxsackievirus B3 infection via a PI3K/Akt dependent pathway.

Publications

The immunity-related GTPase Irgm3 relieves endoplasmic reticulum stress response during coxsackievirus B3 infection via a PI3K/Akt dependent pathway.

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