T-2 Toxin-Induced Apoptosis and c-fos mRNA Expression in Con A-Stimulated Mouse Thymocyte Primary Cultures.

Abstract

Abstract:The development of apoptosis and the expression of c-fos mRNA were investigated up to 24 hours after treatment (HAT) with 0.2 g/ml of T-2 toxin in Con A-stimulated primary thymocyte cultures prepared from BALB/c mice. Cell viability began to decrease from 1 to 3 HAT, and it was approximately 50% at 6 HAT. The level of cytoplasmic nucleosomes peaked at 3 HAT (about 2 times of control) and decreased thereafter. At 6 HAT, thymocytes showed irregular-shaped or fragmented nuclei. By RT-PCR, the level of c-fos mRNA began to increase within 1 HAT, and maintained a high level through the observation period. Preincubation with BAPTA/AM, a intracellular calcium ion chelator, markedly suppressed the expression of c-fos mRNA and the level of DNA fragmentation induced by T-2 toxin. Although less effective, preincubation with H-7, a protein kinase C (PKC) inhibitor, also depressed the above-mentioned two parameters. These findings indicate that, in mouse thymocyte primary cultures treated with T-2 toxin, c-fos may play an important role in the induction of apoptosis and the increase in intracellular calcium ion may be closely related with the expression of c-fos mRNA. In addition, these findings also suggest that PKC-dependent pathway may be involved in T-2 toxin-induced thymocyte apoptosis. (J Toxicol Pathol 2001; 14: 247-251)

T-2 Toxin-induced Toxicity in Pregnant Mice and Rats

“…It is said that the c-fos gene plays an important role in the early phase of T-2 toxin-induced apoptosis in the lymphoid and hematopoietic tissues probably through the synthesis of a certain apoptosis-related protein [ 43 ]. The elevation of c-fos expression requires the mobilization of [Ca 2+ ] i and partially involves a protein kinase C (PKC)-dependent pathway, and the mobilization of [Ca 2+ ] i activates calcium-dependent caspases, resulting in internucleosomal DNA fragmentation [ 44 , 45 ]. T-2 toxin-induced apoptosis in hematopoietic and lymphoid tissues is considered to be independent of the Fas/Fas ligand pathway [ 43 , 46 ] and the p53 -related pathway [ 43 ].…”

Changes in antioxidant status of porcine ovarian granulosa cells after quercetin and T-2 toxin treatment

“…[17] It interferes with the metabolism of membrane phospholipids what can increase lipid peroxides. [18] T-2 toxin induced apoptosis in mouse hepatocytes following the increased expression of oxidative stress-related genes, [19] by generation of ROS. [14] The most prominent molecular target for T-2 toxin is 60S ribosomal subunit.…”