Dataset Information

ALV-J inhibits autophagy through the GADD45?/MEKK4/P38MAPK signaling pathway and mediates apoptosis following autophagy.

ABSTRACT: Autophagy and apoptosis, which are important processes for host immunity, are commonly exploited by viruses to facilitate their survival. However, to the best of our knowledge, very few studies have researched the mechanisms of action of the autophagic and apoptotic signaling pathways following viral infection. Thus, the present study aimed to investigate the mechanisms of action of growth arrest and DNA-damage-inducible ? (GADD45?), an important resistance gene involved in the host resistance to ALV-J. Both ALV-J infection and the overexpression of GADD45? inhibited autophagy during the early stages, which prevented the autophagosomes from binding to the lysosomes and resulted in an incomplete autophagic flux. Notably, GADD45? was discovered to interact with MEKK4 in DF-1 cells. The genetic knockdown of GADD45? and MEKK4 using small interfering RNA-affected ALV-J infection, which suggested that ALV-J may promote the binding of GADD45? to MEKK4 to activate the p38MAPK signaling pathway, which subsequently inhibits autophagy. Furthermore, ALV-J was revealed to affect the autophagic pathway prior to affecting the apoptotic pathway. In conclusion, to the best of our knowledge, the present study was the first to investigate the combined effects of ALV-J infection on autophagy and apoptosis, and to suggest that ALV-J inhibits autophagy via the GADD45?/MEKK4/p38MAPK signaling pathway.

SUBMITTER: Liao Z

PROVIDER: S-EPMC7442830 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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ALV-J inhibits autophagy through the GADD45β/MEKK4/P38MAPK signaling pathway and mediates apoptosis following autophagy.

Liao Zhihong Z Zhang Xinheng X Song Cailiang C Lin Wencheng W Cheng Yuzhen Y Xie Zi Z Chen Sheng S Nie Yu Y Li Aijun A Zhang Huanmin H Li Hongxin H Li Haiyun H Xie Qingmei Q

Cell death & disease 20200812 8

Autophagy and apoptosis, which are important processes for host immunity, are commonly exploited by viruses to facilitate their survival. However, to the best of our knowledge, very few studies have researched the mechanisms of action of the autophagic and apoptotic signaling pathways following viral infection. Thus, the present study aimed to investigate the mechanisms of action of growth arrest and DNA-damage-inducible β (GADD45β), an important resistance gene involved in the host resistance t ...[more]

PMID: 32826872

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Project description:CONTEXTThe effects of the anticancer drug paclitaxel on learning and memory are rarely studied.OBJECTIVEThis study investigated changes in GABAB receptor expression during paclitaxel-induced apoptosis of hippocampal neurons and the role of the p38MAPK/NF-?B pathway in this process.MATERIALS AND METHODSHippocampal neurons isolated from neonatal Sprague-Dawley rats were divided into six groups: Control (C), SB (10?µL of 10-µmol/L SB203580), SN (53?µg/mL SN50), N (1?µmol/L paclitaxel), SB?+?N (10?µmol/L SB203580?+?1?µmol/L paclitaxel) and SN?+?N (53?µg/mL SN50?+?1?µmol/L paclitaxel). Cells in different groups were treated with corresponding agents for 24?h at 37?°C. The apoptosis rate and protein levels of GABAB1 receptors and NF-?B p65 were evaluated. Rat models of neuropathic pain was induced by paclitaxel and were divided into four groups such as N, B?+?N, SN?+?N and SN?+?B?+?N groups. Rats in the N group received intrathecal injections of normal saline solution. Rats in the B?+?N group received intrathecal injections of 10??L baclofen (0.05??g/?L). Rats in the SN?+?N and SN?+?B?+?N groups received intrathecal injections of SN50 and SN50 plus baclofen, respectively. Spatial learning and memory were evaluated in rat models based on the escape latency and the number of crossings over the platform and protein levels of GABAB1 receptors, NF-?B, IL-1? and TNF? were measured by immunohistochemistry assay and western blot.RESULTSThe neuronal apoptosis rate was significantly increased in N (49.16?±?3.12)%, SB?+?N (31.18?±?3.02)% and SN?+?N (28.47?±?3.75)% groups, accompanied by increased levels of GABAB1 receptors and NF-?B p65 (p?<?0.05). The paclitaxel-treated rats demonstrated significantly increased latency (24.32?±?2.94)s and decreased the crossings number (3.14?±?0.63) after 15?d in the Morris water maze (p?<?0.05). Immunohistochemistry assay showed that compared with the N group (GABAB1:9.0?±?1.6, NF-?B p65:29.6?±?2.4, IL-1?: 30.4?±?3.4, TNF?: 31.0?±?3.4), B?+?N, SN?+?N and SN?+?B?+?N groups evidently increased levels of GABAB1 receptor (B?+?N:SN?+?N:SN?+?B?+?N?=?19.4?±?2.1:20.8?±?1.9:28.0?±?1.9) but significantly decreased levels of NF-?B p65 (B?+?N:SN?+?N:SN?+?B?+?N?=?21.2?±?1.5:18.6?±?2.1:12.6?±?1.5), IL-1? (B?+?N:SN?+?N:SN?+?B?+?N?=?22.0?±?1.0:19.6?±?1.8:14.6?±?1.5) and TNF ? (B?+?N:SN?+?N:SN?+?B?+?N?=?23.0?±?1.6:22.2?±?0.8:16.6?±?1.7). Similar findings were found in western blot analysis.DISCUSSIONS AND CONCLUSIONSPaclitaxel may reduce cognitive function in rats through the p38MAPK/NF-?B pathway and GABAB1 receptors.

Dataset Information

ALV-J inhibits autophagy through the GADD45?/MEKK4/P38MAPK signaling pathway and mediates apoptosis following autophagy.

Publications

ALV-J inhibits autophagy through the GADD45β/MEKK4/P38MAPK signaling pathway and mediates apoptosis following autophagy.

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