Gap Junction Protein Connexin 43 as a Target Is Internalized in Astrocyte Neurotoxicity Caused by Di-(2-ethylhexyl) Phthalate

Abstract

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.

IL-6/STAT3/Foxo1 axis as a target of lycopene ameliorates the atrazine-induced thymic mitophagy and pyroptosis cross-talk

“…Additionally, Lyc, a natural bioactive component, is helpful in ameliorating some human diseases. 14 This study unveiled that supplementation of Lyc could mitigate ATZ-induced pyroptosis and mitophagy by blocking the IL-6/STAT3/Foxo1 axis.…”

“…Fruits and vegetables, containing ascorbic acid, carotenoids, and other antioxidative phytochemicals, are helpful for ameliorating human diseases. 14 Lycopene (Lyc), a natural bioactive component, is mainly synthesized by tomatoes and other fruits. Lyc possesses the highest ability as an antioxidant among carotenoids and several antioxidant agents.…”

“…Lyc possesses the highest ability as an antioxidant among carotenoids and several antioxidant agents. 14 Thus, Lyc has attracted attention in clinical trials and research for its application in human disorders. 15,16 Lyc cannot be produced in humans.…”

“…17 The previous studies reported that Lyc played a protective role in cancer and cardiovascular and neurodegenerative diseases. 14 Additionally, numerous studies have revealed the novel role of Lyc in decreasing the toxic effect of environmental risk factors. [18][19][20] Previous studies indicated that Lyc consumption protected the spleen, heart and kidney from ATZ exposure due to its antioxidant properties.…”

Role of Toll-like Receptor/MyD88 Signaling in Lycopene Alleviated Di-2-ethylhexyl Phthalate (DEHP)-Induced Inflammatory Response

“…DEHP is not covalently combined with plastic products; it is continuously released from plastic products and directly penetrates food, water, and air, which can pose a public health threat via dermal absorption, inhalation, and the food chain. , Hence, DEHP has attracted much attention due to its potentially harmful effects. In recent years, studies determined the toxic effects of DEHP in a variety of tissues, such as the liver, kidney, and lungs. − DEHP exposure could cause abnormal expression and dysfunction of the inflammatory response . The spleen is the important organ sensitive to DEHP exposure, and DEHP has been shown to induce damage to the spleen. − Nevertheless, the molecular mechanisms of the effects of long-term low-dose DEHP exposure on the splenic immune and inflammatory response have not been clearly identified.…”