Inhibitors of apoptosis proteins (IAPs) are associated with T-2 toxin-induced decreased collagen II in mouse chondrocytes in vitro. (March 2020)

• Record Type: Journal Article
• Authors: Wang, Wenji; Ji, Yi; Yang, Wenjing; Zhang, Chengzhi; Angwa, Linet; Jin, Baiming; Liu, Juan; Lv, Man; Ma, Wenjing; Yang, Jie; Wang, Kewei
• Is Part Of: Toxicon. Volume 176(2020)
• Page Start: 34
• Page End: 43
• Publication Date: 2020-03
• Subjects: T-2 toxin -- Collagen II -- IAPs -- Chondrocytes -- In vitro; Toxins -- Periodicals; Venom -- Periodicals; 615.9
• DOI: 10.1016/j.toxicon.2020.01.002
• Languages: English
• ISSNs: 0041-0101

Abstract

Abstract: T-2 toxin is considered an unavoidable pollutant, which contaminates food crops and stockpiled cereals, impairing the health of humans and animals due to its multi-organ toxicity. Studies have shown that T-2 toxin can cause articular cartilage damage; however, the underlying molecular mechanism is still unclear. Here, we investigated the possible mechanism of the following inhibitors of apoptosis proteins (IAPs) family members: NAIP, cIAP1, cIAP2, XIAP, and Survivin, and their involvement in T-2 toxin-induced mouse chondrocyte damage. In this study, mouse articular chondrocytes were isolated and cultured in vitro, and the chondrocytes were then treated with 0, 5, 10, and 20 ng/mL T-2 toxin. Firstly, the toxic effect of T-2 toxin on chondrocytes was determined. CCK-8 assay results showed that T-2 toxin induced a dose-dependent inhibition of chondrocyte viability. Transmission electron microscopy demonstrated that T-2 toxin caused morphological changes in chondrocyte endoplasmic reticulum and an increase in mitochondrial swelling. In addition, Annexin-V-FITC/PI staining and caspase 3 protein expression showed that T-2 toxin induced an increase in the apoptotic rate of chondrocytes. Secondly, it was found that T-2 toxin cause decreased expression of cellular and secreted Collagen II. Finally, we examined the expression of NAIP, cIAP1, cIAP2, XIAP, and Survivin in chondrocytes in the presence of T-2 toxin and their relationship with decreased Collagen II. The decrease in Collagen II was negatively correlated with the expression of cIAP1, cIAP2 and positively correlated with NAIP and Survivin mRNA level. Survivin mRNA level had a positive correlation with Collagen II as shown by partial correlation analysis. This study revealed the new role of IAPs in chondrocyte injury and provides new insights and clues into the mechanism of T-2 toxin-induced chondrocyte damage. Highlights: Investigate the toxic mechanism of T-2 toxin in chondrocytes damage using the mouse model in vitro. T-2 toxin results in the decrease of cellular Collagen II and a reduction of secreted collagen II in chondrocytes. Inhibitors of apoptosis proteins (IAPs) are involved in T-2 toxin-induced decreased Collagen II.