Phthalates Induce Neurotoxicity by Disrupting the Mfn2-PERK Axis-Mediated Endoplasmic Reticulum-Mitochondria Interaction.

Di-(2-ethylhexyl) phthalate (DEHP), as the most common phthalate, has been extensively used as a plasticizer to improve the plasticity of agricultural products, which pose severe harm to human health. Mitochondrial dynamics and endoplasmic reticulum (ER) homeostasis are indispensable for maintaining mitochondria-associated ER membrane (MAM) integrity. In this study, we aimed to explore the effect of DEHP on the nervous system and its association with the ER-mitochondria interaction. Here, we showed that DEHP caused morphological changes, motor deficits, cognitive impairments, and blood-brain barrier disruption in the brain. DEHP triggered ER stress, which is mainly mediated by protein kinase R-like endoplasmic reticulum kinase (PERK) signaling. Moreover, DEHP-induced mitofusin-2 (Mfn2) downregulation results in imbalance of the mitochondrial dynamics. Interestingly, DEHP exposure impaired MAMs by inhibiting the Mfn2-PERK interaction. Above all, this study elucidates the disruption of the Mfn2-PERK axis-mediated ER-mitochondria interaction as a phthalate-induced neurotoxicity that could be potentially developed as a novel therapy for neurological diseases.

MAPK/NF-κB signaling mediates atrazine-induced cardiorenal syndrome and antagonism of lycopene.

Atrazine (ATZ) is the most prevalent herbicide that has been widely used in agriculture to control broadleaf weeds and improve crop yield and quality. The heavy use of ATZ has caused serious environmental pollution and toxicity to human health. Lycopene (LYC), is a carotenoid that exhibits numerous health benefits, such as prevention of cardiovascular diseases and nephropathy. However, it remains unclear that whether ATZ causes cardiorenal injury or even cardiorenal syndrome (CRS) and the beneficial role of LYC on it. To test this hypothesis, mice were treated with LYC and/or ATZ for 21 days by oral gavage. This study demonstrated that ATZ exposure caused cardiorenal morphological alterations, and several inflammatory cell infiltrations mediated by activating NF-κB signaling pathways. Interestingly, dysregulation of MAPK signaling pathways and MAPK phosphorylation caused by ATZ have been implicated in cardiorenal diseases. ATZ exposure up-regulated cardiac and renal injury associated biomarkers levels that suggested the occurrence of CRS. However, these all changes were reverted, and the phenomenon of CAR was disappeared by LYC co-treatment. Based on our findings, we postulated a novel mechanism to elucidate pesticide-induced CRS and indicated that LYC can be a preventive and therapeutic agent for treating CRS by targeting MAPK/NF-κB signaling pathways.

Phthalate drives splenic inflammatory response via activating HSP60/TLR4/NLRP3 signaling axis-dependent pyroptosis.

As the most produced phthalate, di-(2-ethylhexyl) phthalate (DEHP) is a widely environmental pollutant primarily used as a plasticizer, which cause the harmful effects on human health. However, the impact of DEHP on spleen and its underlying mechanisms are still unclear. Pyroptosis is a novel form of cell death induced by activating NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes and implicated in pathogenesis of numerous inflammatory diseases. The current study aimed to explore the impact of DEHP on immune inflammatory response in mouse spleen. In this study, the male ICR mice were treated with DEHP (200 mg/kg) for 28 days. Here, DEHP exposure caused abnormal pathohistological and ultrastructural changes, accompanied by inflammatory cells infiltration in mouse spleen. DEHP exposure arouse heat shock response that involves increase of heat shock proteins 60 (HSP60) expression. DEHP also elevated the expressions of toll-like receptor 4 (TLR4) and myeloid differentiation protein 88 (MyD88) proteins, as well as the activation of NF-κB pathway. Moreover, DEHP promoted NLRP3 inflammasome activation and triggered NLRP3 inflammasome-induced pyroptosis. Mechanistically, DEHP drives splenic inflammatory response via activating HSP60/TLR4/NLRP3 signaling axis-dependent pyroptosis. Our findings reveal that targeting HSP60-mediated TLR4/NLRP3 signaling axis may be a promising strategy for inflammatory diseases treatment.

The novel role of the aquaporin water channel in lycopene preventing DEHP-induced renal ionic homeostasis disturbance in mice.

Di-(2-ethylhexyl) phthalate (DEHP), an extensively used plasticizer, can cause environmental pollution and organ injury. Lycopene (LYC) is a natural carotene that has the potential to prevent chronic diseases. To reveal the effect of DEHP and/or LYC on the kidney, male mice were treated with LYC (5 mg/kg) and/or DEHP (500 mg/kg or 1000 mg/kg) by gavage for 28 days. The study indicated that DEHP caused glomerular atrophy, tubular expansion, disappearance of the mitochondrial membrane, and cristae rupture. DEHP exposure can increase the expression of aquaporin (AQP) subunits and the activity of Ca2+-Mg2+-ATPase and decrease the activity of Na+-K+-ATPase, which results in ion disorder. However, LYC can relieve kidney injury by regulating the activity of ATPase, the expression of ATPase subunits, and AQP subunit expression. The results indicated that AQP was a target for LYC in antagonizing the disturbance of DEHP-induced renal damage.

[Effects of simulated acid rain on Quercus glauca seedlings photosynthesis and chlorophyll fluorescence].

Taking the seedlings of Quercus glauca, a dominant evergreen broadleaf tree species in subtropical area, as test materials, this paper studied their photosynthesis, chlorophyll fluorescence, and chlorophyll content under effects of simulated acid rain with pH 2.5, 4.0, and 5.6 (CK). After 2-year acid rain stress, the net photosynthetic rate of Q. glauca increased significantly with decreasing pH of acid rain. The acid rain with pH 2.5 and 4.0 increased the stomatal conductance and transpiration rate, and the effect was more significant under pH 2.5. The intercellular CO2 concentration decreased in the order of pH 2.5 > pH 5.6 > pH 4.0. The maximum photosynthetic rate, light compensation point, light saturation point, and dark respiration rate were significantly higher under pH 2.5 and 4.0 than under pH 5.6, while the apparent quantum yield was not sensitive to acid rain stress. The maximal photochemical efficiency of PS II and the potential activity of PS II under pH 2.5 and 4.0 were significantly higher than those under pH 5.6. The relative chlorophyll content was in the order of pH 2.5 > pH 5.6 > pH 4.0, and there was a significant difference between pH 2.5 and 4.0. All the results suggested that the photosynthesis and chlorophyll fluorescence of Q. glauca increased under the effects of acid rain with pH 2.5 and 4.0, and the acid rain with pH 2.5 had more obvious effects.