2. Academic Validation
  3. Endoplasmic reticulum stress pathway mediates T-2 toxin-induced chondrocyte apoptosis

Endoplasmic reticulum stress pathway mediates T-2 toxin-induced chondrocyte apoptosis

  • Toxicology. 2021 Dec;464:152989. doi: 10.1016/j.tox.2021.152989.
Yi-Nan Liu 1,  Yu-Dong Mu 2,  Hui Wang 3,  Meng Zhang 4,  Ya-Wen Shi 5,  Ge Mi 6,  Lei-Xuan Peng 7,  Jing-Hong Chen 8
Affiliations

Affiliations

  • 1 School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, No. 76 Yanta West Road, Xi'an, 710061, Shaanxi, People's Republic of China. Electronic address: [email protected].
  • 2 Department of Clinical Laboratory, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China. Electronic address: [email protected].
  • 3 School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, No. 76 Yanta West Road, Xi'an, 710061, Shaanxi, People's Republic of China. Electronic address: [email protected].
  • 4 School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, No. 76 Yanta West Road, Xi'an, 710061, Shaanxi, People's Republic of China. Electronic address: [email protected].
  • 5 School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, No. 76 Yanta West Road, Xi'an, 710061, Shaanxi, People's Republic of China. Electronic address: [email protected].
  • 6 School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, No. 76 Yanta West Road, Xi'an, 710061, Shaanxi, People's Republic of China. Electronic address: [email protected].
  • 7 School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, No. 76 Yanta West Road, Xi'an, 710061, Shaanxi, People's Republic of China. Electronic address: [email protected].
  • 8 School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, No. 76 Yanta West Road, Xi'an, 710061, Shaanxi, People's Republic of China. Electronic address: [email protected].
PMID: 34673134 DOI: 10.1016/j.tox.2021.152989
Abstract

T-2 toxin leads to chondrocyte Apoptosis and excessive extracellular matrix degradation. The aim of this study is to investigate if endoplasmic reticulum stress (ERS) - initiated Apoptosis is involved in the chondrocyte damage induced by T-2 toxin. In vivo, rats were divided into a control group, T-2 toxin 200 ng/g BW/d group, the protein levels of GRP78, CHOP, and caspase-12 were detected using immunohistochemistry in articular cartilage tissues. In vitro, C28/I2 and ATDC5 chondrocytes were treated with various concentrations of T-2 toxin. For the salubrinal protection assay, cells were pretreated with 20 μM salubrinal for 1 h, and treated with and without T-2 toxin for 24 h. The cell viability was determined using the MTT assay; and the cell Apoptosis was determined using the Flow Cytometry Assay; the mRNA and protein levels of the ERS markers and ECM were determined using RT-PCR and western blotting. This study found that the expressions of GRP78, CHOP, and caspase-12 is higher in T-2 toxin group than in control group both in vivo and in vitro, and the T-2 toxin administration promoted chondrocyte Apoptosis, suppressed matrix synthesis, and accelerated cellular catabolism via the ERS signaling pathway. In addition, this study found that salubrinal prevented chondrocyte injury by inhibiting ERS-mediated Apoptosis via the PERK-eIF2α-ATF4-CHOP signaling pathway. Collectively, this study provides a new clue to elucidate the mechanism of T-2 toxin-induced chondrocyte damage, and presents a novel therapeutic possibility of salubrinal for Osteoarthropathy such as osteoarthritis (OA) and Kaschin-Beck disease (KBD).

Keywords

CHOP; Caspase-12; ERS; GRP78; Salubrinal; T-2 toxin.

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