2. Academic Validation
  3. Triphenyl phosphate (TPP) promotes hepatocyte toxicity via induction of endoplasmic reticulum stress and inhibition of autophagy flux

Triphenyl phosphate (TPP) promotes hepatocyte toxicity via induction of endoplasmic reticulum stress and inhibition of autophagy flux

  • Sci Total Environ. 2022 Sep 20;840:156461. doi: 10.1016/j.scitotenv.2022.156461.
Miaoran Li 1,  Gang Liu 2,  Li-Xia Yuan 3,  Jing Yang 4,  Jing Liu 4,  Zhijie Li 4,  Chuanbin Yang 5,  Jigang Wang 6
Affiliations

Affiliations

  • 1 Department of Rehabilitation Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Department of Geriatric Medicine, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China.
  • 2 Department of Rehabilitation Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • 3 School of Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515, China.
  • 4 Department of Geriatric Medicine, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China.
  • 5 Department of Geriatric Medicine, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China. Electronic address: [email protected].
  • 6 Department of Geriatric Medicine, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China; School of Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515, China; Artemisinin Research Center, Institute of Chinese Materia Medica, Chinese Academy of Chinese Medical Sciences, Beijing 100700, China. Electronic address: [email protected].
PMID: 35660595 DOI: 10.1016/j.scitotenv.2022.156461
Abstract

Triphenyl phosphate (TPP), a commonly used organophosphate flame retardant, is frequently found in environmental and biota samples, indicating widespread human exposure. Recent studies have shown that TPP causes hepatotoxicity, but the underlying cellular mechanisms are not fully elucidated. Here, by using normal hepatocyte AML12 cells as a model, we showed that TPP induced apoptotic cell death. RNA sequencing analyses revealed that differentially expressed genes induced by TPP were related to endoplasmic reticulum (ER) stress and Autophagy. Immunostaining and western blot results further confirmed that TPP activated ER stress. Interestingly, though TPP increased LC3-II, a canonical marker for Autophagy, TPP inhibited Autophagy flux rather than induced Autophagy. Interestingly, TPP-induced ER stress facilitated Autophagy flux inhibition and Apoptosis. Furthermore, inhibition of Autophagy aggravated, and activation of Autophagy attenuated Apoptosis induced by TPP. Collectively, these results uncovered that ER stress and Autophagy flux inhibition were responsible for TPP-induced Apoptosis in mouse hepatocytes. Thus, our foundlings provided novel insight into the potential mechanisms of TPP-induced hepatocyte toxicity.

Keywords

Apoptosis; Autophagy; ER stress; Hepatoxicity; Triphenyl phosphate.

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