T-2 toxin induces apoptosis, and selenium partly blocks, T-2 toxin induced apoptosis in chondrocytes through modulation of the Bax/Bcl-2 ratio

Chen, Jinghong; Chu, Yangyang; Cao, Junling; Yang, Zhantian; Guo, Xiong; Wang, Zhilun

doi:10.1016/j.fct.2005.09.004

Cited by 66 publications

(62 citation statements)

References 13 publications

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“…T-2 toxin is one of the mycotoxins, a group of type A trichothecenes produced by several fungal genera including Fusarium sp., which is detected in a number of field crops (wheat, maize, barley and oats) and processed grains (malts, beer and bread) (Chen et al, 2006c). It has been more than ten years since T-2 toxin pollution in environment is regarded as the etiology of KBD.…”

Section: Discussionmentioning

confidence: 99%

Promotion of the articular cartilage proteoglycan degradation by T-2 toxin and selenium protective effect

Liu

Cao

Shi

et al. 2008

J. Zhejiang Univ. Sci. B

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Abstract:Objective: To identify the relationship between T-2 toxin and Kashin-Beck disease (KBD), the effects of T-2 toxin on aggrecan metabolism in human chondrocytes and cartilage were investigated in vitro. Methods: Chondrocytes were isolated from human articular cartilage and cultured in vitro. Hyaluronic acid (HA), soluble CD44 (sCD44), IL-1β and TNF-α levels in supernatants were measured by enzyme-linked immunosorbent assay (ELISA). CD44 content in chondrocyte membrane was determined by flow cytometry (FCM). CD44, hyaluronic acid synthetase-2 (HAS-2) and aggrecanases mRNA levels in chondrocytes were determined using reverse transcription polymerase chain reaction (RT-PCR). Immunocytochemical method was used to investigate expressions of BC-13, 3-B-3(−) and 2-B-6 epitopes in the cartilage reconstructed in vitro. Results: T-2 toxin inhibited CD44, HAS-2, and aggrecan mRNA expressions, but promoted aggrecanase-2 mRNA expression. Meanwhile, CD44 expression was found to be the lowest in the chondrocytes cultured with T-2 toxin and the highest in control plus selenium group. In addition, ELISA results indicated that there were higher sCD44, IL-1β and TNF-α levels in T-2 toxin group. Similarly, higher HA levels were also observed in T-2 toxin group using radioimmunoprecipitation assay (RIPA). Furthermore, using monoclonal antibodies BC-13, 3-B-3 and 2-B-6, strong positive immunostaining was found in the reconstructed cartilage cultured with T-2 toxin, whereas no positive staining or very weak staining was observed in the cartilage cultured without T-2 toxin. Selenium could partly inhibit the effects of T-2 toxin above. Conclusion: T-2 toxin could inhibit aggrecan synthesis, promote aggrecanases and pro-inflammatory cytokines production, and consequently induce aggrecan degradation in chondrocytes. These will perturb metabolism balance between aggrecan synthesis and degradation in cartilage, inducing aggrecan loss in the end, which may be the initiation of the cartilage degradation.

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Section: Discussionmentioning

confidence: 99%

Promotion of the articular cartilage proteoglycan degradation by T-2 toxin and selenium protective effect

Liu

Cao

Shi

et al. 2008

J. Zhejiang Univ. Sci. B

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“…A number of mechanisms of cell growth inhibition and apoptosis induction by T-2 toxin have been demonstrated (Holme et al, 2003). Our previous results show that T-2 toxin can inhibit the proliferation of human chondrocytes and induce apoptosis of chondrocytes (Chen et al, 2006). However, the signaling pathways governing apoptosis in mammalian cells are complex and the pro-and anti-apoptotic variations regulate cell survival change according to cell type (Cory and Adams, 2002).…”

Section: Rt-pcr Detection Of Bax Bcl-xl Bcl-2 P53 Fas and Caspasementioning

confidence: 99%

“…After 24 h of culture, DMEM/F12 was replaced by the same medium containing various concentrations (0, 1, 10 and 20 ng/ml) of T-2 toxin. The concentrations of T-2 toxin used in this study were chosen based on results from previously reported 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay (Chen et al, 2006). Cultures were incubated from 1 to 5 d at 37 °C under 5% (v/v) CO 2 .…”

Section: Culture Of Chondrocytes With T-2 Toxinmentioning

confidence: 99%

“…Although the ability of T-2 toxin to produce necrosis and depletion of joint cartilages (Yang, 1995) including chondrocyte apoptosis is well documented (Chen et al, 2006), little is presently known regarding possible signaling pathways in human chondrocytes by this mycotoxin. Using human chondrocytes, we investigated the mechanism by which T-2 toxin induces apoptotic effects and how these effects are modulated by Fas, p53, some of Bcl-2 family proteins and caspases.…”

Section: Introductionmentioning

confidence: 99%

“…Experimentally, it was shown that administration of T-2 toxin for 5 weeks to chicks provoked a syndrome with several features very similar to human Kashin-Beck disease (Yang, 1995). Further, apoptosis of chondrocytes can be induced by T-2 toxin in vitro (1~20 ng/ml) (Chen et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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T-2 toxin-induced apoptosis involving Fas, p53, Bcl-xL, Bcl-2, Bax and caspase-3 signaling pathways in human chondrocytes

Chen

Cao

Chu

et al. 2008

J. Zhejiang Univ. Sci. B

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Abstract:Objective: To investigate the effects of T-2 toxin on expressions of Fas, p53, Bcl-xL, Bcl-2, Bax and caspase-3 on human chondrocytes. Methods: Human chondrocytes were treated with T-2 toxin (1~20 ng/ml) for 5 d. Fas, p53 and other apoptosis-related proteins such as Bax, Bcl-2, Bcl-xL, caspase-3 were determined by Western blot analysis and their mRNA expressions were determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Results: Increases in Fas, p53 and the pro-apoptotic factor Bax protein and mRNA expressions and a decrease of the anti-apoptotic factor Bcl-xL were observed in a dose-dependent manner after exposures to 1~20 ng/ml T-2 toxin, while the expression of the anti-apoptotic factor Bcl-2 was unchanged. Meanwhile, T-2 toxin could also up-regulate the expressions of both pro-caspase-3 and caspase-3 in a dose-dependent manner. Conclusion: These data suggest a possible underlying molecular mechanism for T-2 toxin to induce the apoptosis signaling pathway in human chondrocytes by regulation of apoptosis-related proteins.

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Perfluorooctane sulfonate induces apoptosis in lung cancer A549 cells through reactive oxygen species‐mediated mitochondrion‐dependent pathway

Mao

Xia

Wang

et al. 2012

J of Applied Toxicology

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Perfluorooctane sulfonate (PFOS) is a widespread environmental contaminant that is detected in the lung of mammals. The mechanisms underlying PFOS-induced lung cytotoxicity remain unclear. The main purpose of this study was to evaluate the cytotoxic effects of PFOS on human lung cancer A549 cells and its possible molecular mechanism. A549 cells were treated with PFOS (0, 25, 50, 100 and 200 μm) and the cellular apoptosis, mitochondrial membrane potential as well as intracellular reactive oxygen species were determined. In this study, PFOS induced a dose-dependent increase in A549 cell toxicity via an apoptosis pathway as characterized by increased percentage of sub-G1, activation of caspase-3 and -9, and increased ratio of Bax/bcl-2 mRNA expression. In addition, there was obvious oxidative stress, represented by decreased glutathione level, increased malondialdehyde level and superoxide dismutase activity. N-Acetylcysteine, as an antioxidant that is a direct reactive oxygen species scavenger, can effectively block PFOS-induced reactive oxygen species generation, mitochondrial membrane potential loss and cell apoptosis. These data indicate that PFOS induces apoptosis in A549 cells through a reactive oxygen species-mediated mitochondrial dysfunction pathway mechanism.

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T-2 toxin induces apoptosis, and selenium partly blocks, T-2 toxin induced apoptosis in chondrocytes through modulation of the Bax/Bcl-2 ratio

Cited by 66 publications

References 13 publications

Promotion of the articular cartilage proteoglycan degradation by T-2 toxin and selenium protective effect

Promotion of the articular cartilage proteoglycan degradation by T-2 toxin and selenium protective effect

T-2 toxin-induced apoptosis involving Fas, p53, Bcl-xL, Bcl-2, Bax and caspase-3 signaling pathways in human chondrocytes

Perfluorooctane sulfonate induces apoptosis in lung cancer A549 cells through reactive oxygen species‐mediated mitochondrion‐dependent pathway

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