Table 1.
Organophosphorus compounds induced several diseases mediated by Mitogen-activated protein kinase (MAPK) signaling.
| References | OPC(s)/Dose | Experimental Model | Findings |
|---|---|---|---|
| [30] | Monocrotophos; 10, 100, and 1000 μM | Human Cord Blood Mesenchymal Stem Cells | Increased ROS production through the activation of the ERK/AP-1 pathway |
| [32] | Chlorpyrifos; 0.75 ppm (diluted in 1% sucrose solution) | Drosophila flies | Increased the phosphorylation of p38 and JNK; no changes in the content of total forms of p38 and JNK |
| [34] | Chlorpyrifos; 0–200 μM; 0–24 h | SH-SY5Y cells | Induced cell apoptosis via activation of p38, JNK, and ERK |
| [36] | Phoxim; 4 mg/L added to the diet | Silkworms | Upregulated MAPK and PI3K/Akt signaling pathway genes |
| [37] | Diethyldithiophosphate; 1–50 μM | Human CD4+ T lymphocytes | Stimulated the activation of ERK, JNK, and p38 and NFAT nuclear translocation, leading to a decrease in cell proliferation |
| [38] | Chlorpyrifos; 0, 25, 50, 100, and 200 μM | PC12 cells | Induced apoptosis via activating the p38, JNK, and ERK; activated caspase-3 and cleavage of PARP |
| [39] | Chlorpyrifos; 25, 50, or 100 µM | SH-SY5Y cells | Induced generation of ROS and activation of MAPKs via expression of phospho-Drp1 |
| [5] | Chlorpyrifos; 100 µM | SH-SY5Y cells | Induced apoptosis by producing ROS and upregulating COX-2 mediated by JNK and p38 pathways, independent of the activation of ERK1/2 signaling |
| [40] | Chlorpyrifos; 10 µM | Rat hippocampal neurons | Phosphorylation of ERK1/2 during 96 h exposure; withdrawal after 48 h exposure caused inhibition of ERK1/2 activation, leading to the delayed cytotoxicity in primary rat hippocampal neurons |
| [41] | Chlorpyrifos; 0–80 µM | Primary cortical neurons from embryonic day 17 or neonates rats | Activation of the ERK1/2- and JNK-induced apoptosis; activation of the p38-MAPK prevented apoptosis |
| [42] | Chlorpyrifos; 5 mg/kg, daily | Substantia nigra (SN) in young adults at PND 11–14 | Induced dopaminergic neuronal damage in SN following the inflammatory response activation through NF-kB p65 and p38- MAPK pathways in the nigrostriatal system |
| [43] | Sarin; 80 μg/kg | Wistar rats | In the first 6 h after exposure, fast elevation in the activity of ERK1/2 with no change in JNK that temporarily inhibited apoptosis |
| [44] | Sarin and Soman-like agents; 4.0 mg/kg body weight; Intravenous injection | Wistar rats | Neurotoxicity via activation of JNK following tyrosine kinase phosphorylation |
| [45] | Soman; intramuscular administration; 60 μg kg−1 | Wistar rat cerebellum | Elevated the expression of activated p38-MAPK and c-myc at 14 days after poisoning; c-jun and elk-1 expressions did not change at 14 days after poisoning |
| [46] | Soman; intramuscular administration; 60 μg kg−1 | Rat cerebellar Purkinje cells | Elevated the expression of phosphorylated p38-MAPK and c-myc at 14 days after poisoning; both activated elk-1 and c-jun expressions were not changed at 14 days after poisoning |
| [47] [48] |
Mevinphos, bilateral injection, of 10 nmol | Rostral ventrolateral medulla (RVLM) of rats | No effect on ERK1/2 and the total amount of JNK, p38-MAPK, MAP2K4, and MAP2K6. Increased the phosphorylation of ERK1/2 in Thr202 and Tyr204 and JNK in Thr183 and Tyr185, of p38-MAPK in Thr180 and Tyr182, of MAP2K4 in Ser257 and Thr261, and of MAP2K6 in Ser207 and Thr211 in RVLM and also ATF-2 in Thr71 and of c-Jun in Ser73 death |
| [49] | Mevinphos; 10 nmol; injected bilaterally | Rostral ventrolateral medulla (RVLM) of rats during brain stem death | Stimulated the phosphorylation of ERK1/2 at Thr202 and Tyr204 |
| [50] | Bis(pinacolyl methyl phosphonate); 600 µM | Cultured rat astrocytes | Induced ERK signaling cascade for the induction of mitochondrial vacuolation |
| [51] | Phenyl saligenin phosphate; 0–200 µM | Mitotic and differentiated H9c2 cardiomyoblasts | Induced cytotoxicity by activating JNK1/2 but not ERK1/2 |
| [52] | Chlorpyrifos and dimethoate; 0–1000 µM | Human dendritic cells | Decreased the phosphorylation of Akt 1, Akt 2, Akt, and ERK 2 and caused pulmonary complications.; no effect on the p38 or the JNK |
| [53] | Enantiomers of isocarbophos; 0–40 µM | Human hepatoma cells | (−)-ICP caused modification in Bax/Bcl-2 ratio and hepatotoxicity via sustained activation of the JNK |
| [54] | Tributylphosphate and tris (2-butoxy ethyl) phosphate; 50, 100, and 200 μM | Human hepatoma cells | Induced mitochondrial and p53-mediated apoptosis via activated JNK and TBP also affected ERK1/2 |
| [55] | Tris-(2-chloroethyl)-phosphate; 0.01 and 1 mg/L−1 | Primary cultured renal proximal tubule cells | Elevated the phosphorylation of JNK |
| [56] | Chlorpyrifos; 3–250 µM for 24, 48, and 72 h | Human placental choriocarcinoma (JAR) cells | Activated the p38-MAPK signaling pathway protected against cytotoxicity |
| [57] | Chlorpyrifon-oxon; 50 µM for 40 min | Wild-type (CHOK1) and human muscarinic receptor-expressing Chinese hamster ovary cells (CHO-M2) | Activated the ERK 44/42 signaling through P13-K, PKC, and MEK |
| [58] | Chlorpyrifos-oxon; 0–100 µM | Chinese hamster ovary (CHOK1) | Increased the effect of diacylglycerol on ERK 44/42 activation in dose and time dependent manner |
| [59] | Trichlorfon; 100 µM | Porcine trophectoderm (pTr) and uterine luminal epithelial (pLE) cells | Temporarily activated JNK and p38-MAPK; inhibition of JNK, p38-MAPK, and ERK1/2 decreased the proliferation in pTr cells |
| [60] | Chlorpyrifos; 5–100 µM | Colorectal adenocarcinoma H508 cells | Caused colorectal adenocarcinoma H508 cell growth via involvement of EGFR/ERK1/2 signaling pathway |
| [61] | Chlorpyrifos; 50 µM | MDA-MB-231 and MCF-7 human breast cancer cell lines | Caused cell death through ERK1/2 phosphorylation-mediated |
| [62] | Chlorpyrifos; 0, 25, 50, and 100 µM | SH-SY5Y cells | Caused protein kinase 1 stabilization on the outer mitochondrial membrane; resulted in an elevation in Parkin recruitment from the cytoplasm to the abnormal mitochondria; PINK1 stabilization was modulated by ROS-mediated activation of JNK and ERK1/2 signaling. |
| [63] | Diazinon; 10−4 to 10−5 M | NT2 cells | Reduced the phosphorylated ERK-2 dose-dependently; phosphorylation of Raf-1 did not affect |
| [64] | Paraoxon: 100 µM; Phenyl saligenin phosphate: 0.01, 0.1, and 1.0 µM | SH-SY5Y cells | Paraoxon elevated the activity of the MAPK pathway; Phenyl saligenin phosphate inhibited the activation of the MAPK pathway |
| [65] | Omethoate; 0.5, 1, and 2 mg/kg, PO, 60 days | ICR male mice | At high doses, increased the expression levels of both NF-кB and p38 MAPK; at medium doses, increased the expression of p38-MAPK |
| [66] | Omethoate; 1.5, 3, and 6 mg/kg body through gastric for 2 months | Wistar rats | Increased the levels of MDA, TNF-α, and IL-6 and decreased the activities of SOD and GPx through activation of JNK, p38 MAPK, and NF-κB, leading to insulin resistance. |
| [67] | Chlorpyrifos and cyfluthrin; 0, 25, 50, and 100 µM | Primary human fetal astrocytes | Increased the levels of activated ERK1/2; increased inflammatory markers IL-6 and GFAP |
| [68] | Diazinon; 15 mg/kg, PO | Liver of rats | Induced hyperlipemia and increased levels of LDLr transcription through inhibition of ERK pathway |
Abbrivations: Akt: Protein kinase B, AP-1: Activator protein 1, COX-2: Cyclooxygenase-2, Elk-1: ETS Like-1, ERK: Extracellular signal-regulated protein kinase, GFAP: Glial fibrillary acidic protein, GPx: Glutathione peroxidase, ICP: Isocarbophos, iNOS: inducible nitric oxide synthase JNK: c-Jun NH2-terminal kinase, LDLr: Lipoprotein receptor, MAPKs: Mitogen-activated protein kinases, MEK: Mitogen-activated protein kinase kinase, NF-Κβ: Nuclear transcription factor kappa-β, NO: Nitric oxide, PARP: Poly (ADP-ribose) polymerase, PI3Ks: Phosphoinositide 3-kinases, PKC: Protein kinase C, PKG: Protein Kinase G, PO: Per Os, PTr: Porcine trophectoderm, RVLM: Rostral ventrolateral medulla, Ser73: Phospho-c-Jun, SN: Substantia nigra, SOD: Superoxide dismutase, Thr180/Tyr182: Phospho-p38 MAPK, Thr261: Phospho-SEK1/MKK.