دورية أكاديمية
Mitochondrial dysfunction and endoplasmic reticulum stress induced by activation of PPARα leaded testicular to apoptosis in SD rats explored to di-(2-ethylhexyl) phthalate (DEHP)
| العنوان: | Mitochondrial dysfunction and endoplasmic reticulum stress induced by activation of PPARα leaded testicular to apoptosis in SD rats explored to di-(2-ethylhexyl) phthalate (DEHP) |
|---|---|
| المؤلفون: | Haoyang Zhang, Maohuan Ran, Liping Jiang, Xiance Sun, Tianming Qiu, Jing Li, Ningning Wang, Xiaofeng Yao, Cong Zhang, Haoyuan Deng, Shaopeng Wang, Guang Yang |
| المصدر: | Ecotoxicology and Environmental Safety, Vol 268, Iss , Pp 115711- (2023) |
| بيانات النشر: | Elsevier, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Environmental pollution LCC:Environmental sciences |
| مصطلحات موضوعية: | DEHP, Apoptosis, PPARα, Mitochondrial dysfunction, Endoplasmic reticulum stress, Environmental pollution, TD172-193.5, Environmental sciences, GE1-350 |
| الوصف: | Di-2-ethylhexyl phthalate (DEHP), as a common endocrine disrupting chemicals, can induce toxicity to reproductive system. However, the mechanism remains to be explored. In our study, DEHP exposure induced testicular injury in rats. The high throughput transcriptional sequencing was performed to identify differentially expressed genes (DEGs) between the treatment and control groups. KEGG analysis revealed that DEGs were enriched in apoptosis, PPARα, and ER stress pathway. DEHP up-regulated the expression of PPARα, Bax, Bim, caspase-4. GRP78, PERK, p-PERK, eIF2α, p-eIF2α, ATF4 and CHOP. This view has also been confirmed in TM3 and TM4 cells. In vitro, after pre-treatment with GW6471 (an inhibitor of PPARα) or GSK (an inhibitor of PERK), the apoptosis was inhibited and mitochondrial dysfunction was improved. Moreover, the improvement of mitochondrial dysfunction decreased the expression of PERK pathway by using SS-31(a protective agent for mitochondrial function). Interestingly, ER stress promoted the accumulation of ROS by ERO1L (the downstream of CHOP during ER stress), and the ROS further aggravated the ER stress, thus forming a feedback loop during the apoptosis. In this process, a vicious cycle consisting of PERK, eIF2α, ATF4, CHOP, ERO1L, ROS was involved. Taken together, our results suggested that mitochondrial dysfunction and ER stress-ROS feedback loop caused by PPARα activation played a crucial role in DEHP-induced apoptosis. This work provides insight into the mechanism of DEHP-induced reproductive toxicity. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 0147-6513 |
| العلاقة: | http://www.sciencedirect.com/science/article/pii/S0147651323012150Test; https://doaj.org/toc/0147-6513Test |
| DOI: | 10.1016/j.ecoenv.2023.115711 |
| الوصول الحر: | https://doaj.org/article/017247dc12eb463f9a68507e91a4ca14Test |
| رقم الانضمام: | edsdoj.017247dc12eb463f9a68507e91a4ca14 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 01476513 |
|---|---|
| DOI: | 10.1016/j.ecoenv.2023.115711 |