ABSTRACT
Di-(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer in plastic products, consumer products, and packaging materials. It is of great health concern in both animals and humans as it released into the environment and entered into the body from plastic products over time, thereby resulting in neurotoxicity. As a pivotal regulator of the central nervous system (CNS), astrocytes, are crucial for maintaining brain homeostasis. Nevertheless, the underlying reason for astrocyte neurotoxicity due to DEHP exposure remains incompletely understood. Here, using an in vivo model of neurotoxicity in quail, this study summarizes that Cx43 is internalized by phosphorylation and translocated to the nucleus as a consequence of DEHP exposure in astrocytes. This study further demonstrated that astrocytes transformed to pro-inflammatory status and induced the formation of autophagosomes. Of note, integrated immunofluorescent codetection approaches revealed an overexpression of the glial fibrillary acidic protein (GFAP) and down-expression of Cx43 in astrocytes. Therefore, in terms of neurotoxicity, this experiment in vivo models directly linked Cx43 internalization to autophagy and neuroinflammation and ultimately locked these changes to the astrocytes of the brain. These findings unveil a potential approach targeting Cx43 internalization for the treatment of neurodegeneration caused by DEHP exposure in astrocytes.
Subject(s)
Diethylhexyl Phthalate , Neurotoxicity Syndromes , Animals , Astrocytes/metabolism , Connexin 43/genetics , Connexin 43/metabolism , Connexins/metabolism , Diethylhexyl Phthalate/metabolism , Diethylhexyl Phthalate/toxicity , Neurotoxicity Syndromes/genetics , Neurotoxicity Syndromes/metabolism , Phthalic Acids , Plastics/metabolismABSTRACT
ObjectiveTo investigate the effect of heart-regulating and mind-calming acupuncture on the expression of gap junction protein connexin43 (Cx43) in myocardial cells in a rabbit model of ventricular arrhythmia.MethodA rabbit model of ventricular arrhythmia was made by injecting barium chloride into the marginal ear vein. Forty New Zealand rabbits were randomized into control, model, acupuncture and medication groups. The acupuncture group received heart-regulating and mind-calming acupuncture[at Lingtai(GV10), Shendao(GV11), bilateral Neiguan(PC6)and Baihui(GV20)]and the medication group, oral gavage of propafenone. Rabbit left ventricle was taken after the completion of the experiment. Cx43 expressions were compared and analyzed usingan immunohistochemical staining technique and a computer image processing system.ResultCx43 expression decreased significantly in the model group compared with the control group (P0.05).Conclusion Adjusting Cx43 expression in myocardial cells may be one of the target points for this acupuncture treatment of arrhythmia.
