Organophosphorus Compounds and MAPK Signaling Pathways

Farkhondeh, Tahereh; Buhrmann, Constanze; Pourbagher‐Shahri, Ali Mohammad; Shakibaei, Mehdi; Samarghandian, Saeed

doi:10.3390/ijms21124258

Cited by 64 publications

(28 citation statements)

References 65 publications

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“…Several studies (31)(32)(33) have reported that JNK translocates to the nucleus after its activation and is involved in cellular functions via the phosphorylation of transcription factors in the nucleus. However, some studies (11,(34)(35)(36) have suggested that JNK not only serves a role in the nucleus, but also in the localization and regulation in other parts of the cells by binding to a specific protein, such as Sab (11).…”

Section: Discussionmentioning

confidence: 99%

Selective inhibition of JNK mitochondrial location is protective against seawater inhalation‑induced ALI/ARDS

Liu

et al. 2021

Mol Med Rep

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Localization of phosphorylated (p)-JNK to the mitochondria can lead to functional mitochondrial disorder, resulting in a decrease in energy supply and membrane potential, as well as an increase in reactive oxygen species production and apoptosis. JNK is involved in the occurrence of acute lung injury (ALI), and activation of the JNK pathway is one of the crucial factors resulting in injury. The aim of the present study was to investigate whether the JNK-mitochondria (mitoJNK) location participated in the occurrence of ALI and acute respiratory distress syndrome (ALI/ARDS). The present study examined the activation of the JNK pathway, the content of JNK located on the mitochondria and the treatment effects of a cell-permeable peptide Tat-Sab KIM1 , which can selectively inhibit the location of JNK on mitochondria. The expression levels of proteins were detected by western blot analysis. Lung injuries were evaluated by histological examination, wet-to-dry weight ratios, and H 2 O 2 and malondialdehyde concentrations in the lung tissues. Lung cells apoptosis was evaluated using TUNEL assay. The results demonstrated that JNK was phosphorylated and activated during seawater inhalation-induced ALI/ARDS, not only in the routine JNK pathway but also in the mitoJNK pathway. It was also found that Tat-Sab KIM1 could specifically inhibit JNK localization to mitochondria and the activation of mitoJNK signaling. Furthermore, Tat-Sab KIM1 could inhibit Bcl-2-regulated autophagy and mitochondria-mediated apoptosis. In conclusion, mitoJNK localization disrupted the normal physiological functions of the mitochondria during ALI/ARDS, and selective inhibition of JNK and mitochondrial SH3BP5 (also known as Sab) binding with Tat-Sab KIM1 can block deterioration from ALI/ARDS.

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Section: Discussionmentioning

confidence: 99%

Selective inhibition of JNK mitochondrial location is protective against seawater inhalation‑induced ALI/ARDS

Liu

et al. 2021

Mol Med Rep

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“…The MAPK signaling pathway is commonly stimulated by a plethora of stress conditions and inflammatory cytokines, resulting in a cascade of phosphorylation and other signaling events that initiate changes for the appropriate biological response (cellular adaptation for survival or death) [ 53 , 54 ]. Many members of the MAPK family of proteins are implicated in a number of neuroinflammatory diseases [ 55 , 56 ], and previous research has shown that the MAPK signaling pathway is activated by AChEIs [ 56 , 57 ], which drives the neuroinflammatory effects of AChEI exposure. Two of the main families of MAPKs were measured in this study: extracellular signal-regulated kinases (ERKs) and c-Jun N-terminal kinases (JNKs).…”

Section: Discussionmentioning

confidence: 99%

Differential phosphoprotein signaling in the cortex in mouse models of Gulf War Illness using corticosterone and acetylcholinesterase inhibitors

Penatzer

Miller

Prince

et al. 2021

Heliyon

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Veterans from the 1990-91 Gulf War were exposed to acetylcholinesterase inhibitors (AChEIs), and, following service, an estimated one-third began suffering from a medically unexplained, multi-symptom illness termed Gulf War Illness (GWI). Previous research has developed validated rodent models that include exposure to exogenous corticosterone (CORT) and AChEIs to simulate high stress and chemical exposures encountered in theater. This combination of exposures in mice resulted in a marked increase in neuroinflammation, which is a common symptom of veterans suffering from GWI. To further elucidate the mechanisms associated with these mouse models of GWI, an investigation into intracellular responses in the cortex were performed to characterize the early cellular signaling changes associated with this exposure-initiated neuroinflammation.Main methods: Adult male C57BL/6J mice were exposed to CORT in the drinking water (200 μg/mL) for 7 days followed by a single intraperitoneal injection of diisopropyl fluorophosphate (DFP; 4.0 mg/kg) or chlorpyrifos oxon (CPO; 8.0 mg/kg), on day 8 and euthanized 0.5, 2, and 24 h post-injection. Eleven post-translationally modified protein targets were measured using a multiplexed ELISA. Key findings: Phosphoprotein responses were found to be exposure specific following AChEI insult, with and without CORT. Specifically, CORT þ CPO exposure was found to sequentially activate several phosphoproteins involved in mitogen activated protein kinase signaling (p-MEK1/2, p-ERK1/2, and p-JNK). DFP alone similarly increased proteins in this pathway (p-RPS6, and p-JNK), but the addition of CORT ameliorated these affects. Significance: The results of this study provide insight into differentially activated pathways depending on AChEI in these GWI models.

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“…Since the metabolism of astrocytes is an in dissociable link between neuronal health and synaptic functions, it is important to be mindful of how environmental toxicants can impact human health. Furthermore, environmental toxicant exposure can result in glucose dysfunction, including the involvement of the GLUT1 transporter, especially the astrocyte-specific transporter [13] . Within the CNS, there is an overlap between the peripheral and astrocytic mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Effect of Oral Administration of Paraquat Pesticide on the Hippocampus and Substantia Nigra in Wistar Rats' Brains

Zaalan¹,

Qassem²,

Zaalan³

et al. 2021

Journal of Agricultural, Environmental and Veterinary Sciences

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This study aimed to detect the neurohistological damages of chronic exposure to low levels of pesticide (paraquat) in the hippocampus, and substantia nigra in Wistar rats' brains. The neurotoxic effects of acute poisoning are well established but the possibility that low level exposure causes different diseases is controversialIt is important to get a clear answer to this question as more individuals are at risk of low level exposure than acute poisoning. The anatomical and histological of current study to affected brains showed cells display the cytological changes of herbisecticides-lesioned brain tissue, such as a significant decrease in the size of the brain was observed, as most of its external features disappeared. in addition, we detected vacuolization around cells that degenerated because many reasons like apoptosis or necrosis, and the intracellular neurofibrillary tangles were observed at many regions such as the hippocampus and substantia nigra. Moreover extracellular amyloid plaques take fibers form were detected. we also observed degenerated in CA1, CA2 and CA3 regions (molecular layer, polymorphic layer and pyramidal layer) by pigmenting degenerated neurons with silver nitrate with increased astrocytes of glia cells.

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Organophosphorus Compounds and MAPK Signaling Pathways

Cited by 64 publications

References 65 publications

Selective inhibition of JNK mitochondrial location is protective against seawater inhalation‑induced ALI/ARDS

Selective inhibition of JNK mitochondrial location is protective against seawater inhalation‑induced ALI/ARDS

Differential phosphoprotein signaling in the cortex in mouse models of Gulf War Illness using corticosterone and acetylcholinesterase inhibitors

Effect of Oral Administration of Paraquat Pesticide on the Hippocampus and Substantia Nigra in Wistar Rats' Brains

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