T-2 toxin induces apoptosis via the Bax-dependent caspase-3 activation in mouse primary Leydig cells

Abstract

To explore the toxic effect of T-2 toxin on mouse Leydig cells and its underlying molecular mechanisms, we isolated Leydig cells from mature mice, set-up Leydig cells culture, treated cells with T-2 toxin, evaluated cell proliferation, detected the caspase-3 activity, mitochondrial activity and apoptosis rate, and measured the mRNA levels of Bcl-2, Bax, PARP and caspase-3. T-2 toxin inhibited cell proliferation at concentrations higher than 10 M or time more than 12 h, T-2 toxin also decreased Bcl-2 expression at the mRNA levels and mitochondrial activity at concentrations higher than 10 M. While, T-2 toxin increased the mRNA expressions of Bax and PARP at concentrations higher than 10 M and 10 M, respectively, triggered mitochondria-mediated apoptosis, activated downstream caspase-3, and then increased caspase-3 at the activity and mRNA levels at concentrations higher than 10 M. These data showed that T-2 toxin appears to activate specific intracellular death-related pathways leading to Bax-dependent caspase-3 activation and the induction of apoptosis in Leydig cells.

Delayed effects of autophagy on T-2 toxin-induced apoptosis in mouse primary Leydig cells

“…A wealth of research papers clearly indicate a negative influence of T-2 toxin on the hematocytes, hepatocytes, chondrocytes, intestinal function, immune system, and reproductive system (Adhikari et al, 2017; He et al, 2012; Huang et al, 2018; Leal et al, 1998; Moosavi et al, 2016; Wu et al, 2017; Yang et al, 2010; Zhang et al, 2018). Our research team has also reported the negative effects of T-2 toxin on male fertility and other reproductive pathologies in male animals (Yang et al, 2010).…”

“…The isolation and purification of Leydig cells were performed according to our previous methods (Zhang et al, 2018). In brief, Leydig cells were isolated from testes of 60- to 90-day Kunming mice.…”

“…Ingestion by humans or livestock of cereals contaminated by T-2 toxin can cause adverse reactions (De Ruyck et al, 2015; Escrivá et al, 2015; Nesic et al, 2014). T-2 toxin could induce apoptosis in mouse Leydig cells (Zhang et al, 2018), thymocytes (Islam et al, 1998), lymphocytes (Shinozuka et al, 1997), human chondrocytes (Liu et al, 2014), human neuroblastoma cells (Agrawal et al, 2015), and rat ovarian granulosa cells (Wu et al, 2013). However, little is known about the functions of T-2 toxin on autophagy and the cross talk between autophagy and apoptosis in male reproduction.…”

Mycotoxins and oxidative stress: where are we?

“…The oxidative stress induced by T-2 promotes Fas upregulation, p53 activation, down-regulation of Bcl-2 and up-regulation of the pro-apoptotic factor Bax causing cytochrome C release, caspase 3 activation and cell apoptosis (Chen et al, 2008;Zhang et al, 2018) ( Figure 2). ROS generation causes a decrease in Nrf2 expression, changes in the intracellular antioxidant enzymes GPx, GR, SOD and CAT, promoting a decrease in GSH level and an increase in MDA level (Wu et al, 2014b;Yang et al, 2016).…”

l‐arginine protects against oxidative damage induced by T‐2 toxin in mouse Leydig cells

“…T‐2 toxin, a trichothecene mycotoxin produced by several species of Fusarium , has hepatotoxic, hematotoxic, immunotoxic, and genotoxic properties . Previous studies have provided evidence that T‐2 toxin can induce testicular oxidative damage and cause apoptosis in mouse Leydig cells …”