2. Academic Validation
  3. Lonp1 and Sig-1R contribute to the counteraction of ursolic acid against ochratoxin A-induced mitochondrial apoptosis

Lonp1 and Sig-1R contribute to the counteraction of ursolic acid against ochratoxin A-induced mitochondrial apoptosis

  • Food Chem Toxicol. 2022 Dec 29;172:113592. doi: 10.1016/j.fct.2022.113592.
Qipeng Zhang 1,  Wenying Chen 2,  Boyang Zhang 3,  Yiwen Zhang 2,  Yuqing Xiao 2,  Yichen An 2,  Lingyun Han 2,  Huiqiong Deng 2,  Song Yao 2,  Hongwei Wang 2,  Xiao Li Shen 4
Affiliations

Affiliations

  • 1 School of Public Health, Zunyi Medical University, Zunyi, 563000, Guizhou, PR China; Depatment of Hospital Infection Control, The Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou, PR China.
  • 2 School of Public Health, Zunyi Medical University, Zunyi, 563000, Guizhou, PR China.
  • 3 Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, 100083, PR China.
  • 4 School of Public Health, Zunyi Medical University, Zunyi, 563000, Guizhou, PR China. Electronic address: [email protected].
PMID: 36587836 DOI: 10.1016/j.fct.2022.113592
Abstract

Ochratoxin A (OTA), a secondary Fungal metabolite with nephrotoxicity, is widespread in numerous kinds of feeds and foodstuffs. Ursolic acid (UA), a water-insoluble pentacyclic triterpene acid, exists in a wide range of food Materials and medicinal Plants. Our earlier researches provided preliminary evidence that mitochondria- and mitochondria-associated endoplasmic reticulum membranes (MAMs)-located stress-responsive Lon protease 1 (Lonp1) had a protective function in OTA-induced nephrotoxicity, and the renoprotective function of UA against OTA partially due to Lonp1. However, whether other MAMs-located protiens, such as endoplasmic reticulum stress (ERS)-responsive Sigma 1-type Opioid Receptor (Sig-1R), contribute to the protection of UA against OTA-induced nephrotoxicity together with Lonp1 needs further investigation. In this study, the cell viability, Reactive Oxygen Species, and protein expressions of human proximal tubule epithelial-originated kidney-2 (HK-2) cells varied with OTA and/or UA/CDDO-me/AVex-73/Sig-1R siRNA treatments were determined. Results indicated that a 24 h-treatment of 5 μM OTA could significantly induce mitochondrial-mediated Apoptosis via repressing Lonp1 and Sig-1R, thereby enhancing the protein expressions of GRP78, p-PERK, p-eIF2α, CHOP, IRE1α, and Bax, and inhibiting the protein expression of Bcl-2 in HK-2 cells, which could be remarkably relieved by a 2 h-pre-treatment of 4 μM UA (P < 0.05). In conclusion, through mutual promotion between Lonp1 and Sig-1R, UA could effectively relieve OTA-induced Apoptosis in vitro and break the vicious cycle between oxidative stress and ERS, which activated the mitochondrial Apoptosis pathway.

Keywords

Apoptosis; Endoplasmic reticulum stress; Mitochondria-associated ER membranes; Mycotoxin; Nephrotoxicity; Pentacyclic triterpenoid.

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