Ferroptosis is critical for phthalates driving the blood-testis barrier dysfunction via targeting transferrin receptor

Zhao, Yi; Zhang, Hao; Cui, Jia-Gen; Wang, Jiaxin; Chen, Ming-Shan; Wang, Haoran; Li, Xue-Nan; Li, Jinlong

doi:10.1016/j.redox.2022.102584

Cited by 81 publications

(27 citation statements)

References 78 publications

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“…22 Numerous studies have shown that DEHP and its metabolites can cause testicular injury and spermatogenic impairment through the induction of apoptosis, iron death and oxidative stress. 20,29,[44][45][46] Melatonin has multiple biological activities, such as antioxidant, anti-inflammatory, and anti-apoptotic activities. 36 It has been reported that Melatonin alleviated testicular damage in mice caused by DEHP exposure.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of melatonin on DEHP‐induced apoptosis and oxidative stress in prepubertal testes via the PI3K/AKT pathway

Chen,

Zhao,

Zheng

et al. 2023

Environmental Toxicology

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Di(2‐ethylhexyl) phthalate (DEHP), an environmental endocrine disruptor, is one of the most common plasticizers and is widely used in various plastic products. DEHP induces apoptosis and oxidative stress and has been shown to have androgenic toxicity. However, the methods to combat DEHP‐induced testicular damage and the mechanisms involved remain to be elucidated. In the present study, we used melatonin, which has strong antioxidant properties, to intervene in prepubertal mice and mouse Leydig cells (TM3) treated with DEHP or its metabolite mono(2‐ethylhexyl) phthalate (MEHP). The results showed that melatonin protected against DEHP‐induced testicular damage in prepubertal mice, mainly by protecting against DEHP‐induced structural destruction of the germinal tubules and by attenuating the DEHP‐induced decrease in testicular organ coefficients and testosterone levels. Transcriptomic analysis found that melatonin may attenuate DEHP‐induced oxidative stress and apoptosis in prepubertal testes. In vitro studies further revealed that MEHP induces oxidative stress injury and increases apoptosis in TM3 cells, while melatonin reversed this damage. In vitro studies also found that MEHP exposure inhibited the expression levels of molecules related to the PI3K/AKT signaling pathway, and melatonin reversed this change. In conclusion, these findings suggest that melatonin protects against DEHP‐induced prepubertal testicular injury via the PI3K/AKT signaling pathway, and provide a theoretical basis and experimental rationale for combating male reproductive dysfunction.

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Section: Discussionmentioning

confidence: 99%

Protective effects of melatonin on DEHP‐induced apoptosis and oxidative stress in prepubertal testes via the PI3K/AKT pathway

Chen,

Zhao,

Zheng

et al. 2023

Environmental Toxicology

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“…For histopathological analysis, tissue sections were processed for paraffin. Then, tissue sections were stained with hematoxylin and eosin (H&E) and 0.75% toluidine blue as previously described. − Optical microscopes were used to examine all sections. Using a semiquantitative blind method, six brains from each group were randomly selected and the number of neurons in the striatum was counted.…”

Section: Methodsmentioning

confidence: 99%

Cadmium Transforms Astrocytes into the A1 Subtype via Inducing Gap Junction Protein Connexin 43 into the Nucleus

Zhao

Tang

et al. 2023

J. Agric. Food Chem.

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Cadmium is highly toxic and present in the environment and can be accumulated among various levels of the food chain. Both humans and animals are at risk from toxicity associated with cadmium. However, the neurological endpoint caused by cadmium has not been revealed. The aim of our research is to explore the potential target of cadmium attack when causing neurotoxicity. 80 male chickens (one day old, weighing 36.49 ± 2.88 g) were randomly divided into four groups and independently treated with 0, 35, 70, or 140 mg/kg CdCl 2 in diet for 90 days. The result showed that the striatum was damaged due to a high dose of cadmium in the brain, which was characterized by degeneration of neurons and astrocyte dysfunction. Transcriptome analysis demonstrated that striatal astrocytes were transformed into the A1 state under cadmium exposure. Deeper investigation revealed that the internalization of gap junction protein connexin 43 was responsible for this transformation. Eventually, we can conclude that the internalized gap junction protein connexin 43 of astrocytes is the target of cadmium anchoring, and this process was accompanied by the transformation of astrocytes into the A1 subtype. This study provides a new direction for exploring the effects of cadmium on the nervous system and the treatment of subsequent nervous system diseases.

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“…With the method of Zhao et al 27 and Liu et al 28 , total RNA was obtained from duck renal tubular epithelial cells utilizing TransZol Up (TransGen Biotech, Beijing, China). RNA was reverse transcribed using HiScript ® III RT SuperMix for qPCR (Vazyme, China).…”

Section: Real-time Quantitative Pcr (Rt-qpcr) Assaymentioning

confidence: 99%

Role of PLC/IP₃/IP₃R axis in excess molybdenum exposure induced apoptosis in duck renal tubular epithelial cells

Guo,

Zhang,

et al. 2023

Environmental Toxicology

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Excess molybdenum (Mo) is harmful to animals, but its nephrotoxicity has not been comprehensively explained. To appraise the influences of excess Mo on Ca homeostasis and apoptosis via PLC/IP3/IP3R axis, primary duck renal tubular epithelial cells were exposed to 480 μM and 960 μM Mo, and joint of 960 μM Mo and 10 μM 2‐APB or 0.125 μM U‐73122 for 12 h (U‐73122 pretreated for 1 h), respectively. The data revealed that the increment of [Ca2+]c induced by Mo mainly originated from intracellular Ca storage. Mo exposure reduced [Ca2+]ER, elevated [Ca2+]mit, [Ca2+]c, and the expression of Ca homeostasis‐related factors (Calpain, CaN, CRT, GRP94, GRP78 and CaMKII). 2‐APB could effectively reverse subcellular Ca2+ redistribution by inhibiting IP3R, which confirmed that [Ca2+]c overload induced by Mo originated from ER. Additionally, PLC inhibitor U‐73122 remarkably mitigated the change, and dramatically reduced the number of apoptotic cells, the expression of Bak‐1, Bax, cleaved‐Caspase‐3/Caspase‐3, and notably increased the expression of Bcl‐xL, Bcl‐2, and Bcl‐2/Bax ratio. Overall, the results confirmed that the Ca2+ liberation of ER via PLC/IP3/IP3R axis was the main cause of [Ca2+]c overload, and then stimulated apoptosis in duck renal tubular epithelial cells.

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Ferroptosis is critical for phthalates driving the blood-testis barrier dysfunction via targeting transferrin receptor

Cited by 81 publications

References 78 publications

Protective effects of melatonin on DEHP‐induced apoptosis and oxidative stress in prepubertal testes via the PI3K/AKT pathway

Protective effects of melatonin on DEHP‐induced apoptosis and oxidative stress in prepubertal testes via the PI3K/AKT pathway

Cadmium Transforms Astrocytes into the A1 Subtype via Inducing Gap Junction Protein Connexin 43 into the Nucleus

Role of PLC/IP₃/IP₃R axis in excess molybdenum exposure induced apoptosis in duck renal tubular epithelial cells

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Ferroptosis is critical for phthalates driving the blood-testis barrier dysfunction via targeting transferrin receptor

Cited by 81 publications

References 78 publications

Protective effects of melatonin on DEHP‐induced apoptosis and oxidative stress in prepubertal testes via the PI3K/AKT pathway

Protective effects of melatonin on DEHP‐induced apoptosis and oxidative stress in prepubertal testes via the PI3K/AKT pathway

Cadmium Transforms Astrocytes into the A1 Subtype via Inducing Gap Junction Protein Connexin 43 into the Nucleus

Role of PLC/IP3/IP3R axis in excess molybdenum exposure induced apoptosis in duck renal tubular epithelial cells

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Role of PLC/IP₃/IP₃R axis in excess molybdenum exposure induced apoptosis in duck renal tubular epithelial cells