Central role of TRAP1 in the ameliorative effect of oleanolic acid on the mitochondrial-mediated and endoplasmic reticulum stress-excitated apoptosis induced by ochratoxin A. (28th February 2021)

• Record Type: Journal Article
• Authors: Zhang, Qipeng; Chen, Wenying; Zhang, Boyang; Li, Chen; Zhang, Xunyao; Wang, Qian; Wang, Yan; Zhou, Qian; Li, Xiaohong; Shen, Xiao Li
• Is Part Of: Toxicology. Volume 450(2021)
• Publication Date: 2021-02-28
• Subjects: Mycotoxin -- Oleanolic acid -- Protein homeostasis -- Tumor necrosis factor receptor-associated protein 1 -- ER-mitochondria crosstalk; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2021.152681
• Languages: English
• ISSNs: 0300-483X

Abstract

Highlights: Ochratoxin A (OTA) induced mitochondrial-mediated and ER stress-excitated apoptosis. Oleanolic acid (OA) could alleviate OTA-induced apoptosis. Tumor necrosis factor receptor-associated protein 1 (TRAP1) could inhibit apoptosis. TRAP1 played a central role in the ameliorative effect of OA on OTA nephrotoxicity. Abstract: Ochratoxin A (OTA) is a nephrotoxic mycotoxin that is widely distributed in foodstuffs and feeds, meanwhile oleanolic acid (OA) is ubiquitous in various fruit skins, food materials, and medicinal herbs. Due to that OA has a nephroprotective effect, it has the poteintial to counteract OTA-induced nephrotoxicity by nutritional intervention of OA. Furthermore, tumor necrosis factor receptor-associated protein 1 (TRAP1) acts as the core of endoplasmic reticulum (ER)-mitochondria crosstalk, becoming our focus in the mechanism investigation. In this study, the cell viability, apoptosis rate, and protein expressions of human proximal tubule epithelial-originated kidney-2 (HK-2) cells in response to OTA and/or OA were determined. Results indicated that a 24 h-treatment of 1-5 μM OTA could notably induce mitochondrial-mediated and ER stress (ERS)-excitated apoptosis via inhibiting TRAP1, thereby activating CypD, Bax, Cyt-C, Cleaved Caspase-9, Cleaved Caspase-3, GRP78, p-PERK, p-eIF2α, ATF4, and CHOP and inhibiting Bcl-2 ( P < 0.05). Results of the RNA interference of TRAP1 further ascertained its anti-apoptotic function via inhibiting CypD, Bax, GRP78, and CHOP and enhancing Bcl-2 ( P < 0.05). The pre-treatment of 2 μM OA for 2 h could remarkably relieve OTA-induced suppression of TRAP1 ( P < 0.05). In conclusion, TRAP1 played a central role in the ameliorative effect of OA on the mitochondrial-mediated and ERS-excitated apoptosis induced by OTA.