Jones C, Ciacci-Zanella J R, Zhang Y, Henderson G, Dickman M
Center for Biotechnology, Department of Veterinary and Biomedical Sciences, University of Nebraska-Lincoln, East Campus Loop, Lincoln, Nebraska, USA.
Environ Health Perspect. 2001 May;109 Suppl 2(Suppl 2):315-20. doi: 10.1289/ehp.01109s2315.
Fumonisins are mycotoxins produced by Fusarium moniliforme, a prevalent fungus that infects corn and other cereal grains. Fumonisin B1(FB1 is the most common mycotoxin produced by F. moniliforme, suggesting it has toxicologic significance. The structure of FB1 resembles sphingoid bases, and it inhibits ceramide synthase. Because sphingoid bases regulate cell growth, differentiation, transformation, and apoptosis, it is not surprising to find that FB1 can alter growth of certain mammalian cells. Previous studies concluded FB1-induced apoptosis, or cell cycle arrest, in African green monkey kidney fibroblasts (CV-1). In this study we have identified genes that inhibit FB1 induced apoptosis in CV-1 cells and two mouse embryo fibroblasts (MEF). A baculovirus gene, inhibitor of apoptosis (CpIAP), protected these cells from apoptosis. CpIAP blocks apoptosis induced by the tumor necrosis factor (TNF) pathway as well as other mechanisms. Further support for the involvement of the TNF signal transduction pathway in FB1 induced apoptosis was the cleavage of caspase 8. Inhibition of caspases by the baculovirus gene (italic)p35 also inhibited FB1-induced apoptosis. The tumor suppressor gene p53 was not required for FB1 induced apoptosis because p53-/- MEF undergo apoptosis following FB1 treatment. Furthermore, Bcl-2 was not an effective inhibitor of FB1-induced apoptosis in CV-1 cells or p53+/+ MEF. In summary, these results provide new information to help understand the mechanism by which FB1 induces apoptosis.
伏马毒素是由串珠镰刀菌产生的霉菌毒素，串珠镰刀菌是一种常见的真菌，可感染玉米和其他谷物。伏马毒素B1（FB1）是串珠镰刀菌产生的最常见的霉菌毒素，表明它具有毒理学意义。FB1的结构类似于鞘脂碱，它能抑制神经酰胺合成酶。由于鞘脂碱调节细胞生长、分化、转化和凋亡，因此发现FB1能改变某些哺乳动物细胞的生长也就不足为奇了。先前的研究得出结论，FB1可诱导非洲绿猴肾成纤维细胞（CV-1）发生凋亡或细胞周期停滞。在本研究中，我们鉴定了在CV-1细胞和两种小鼠胚胎成纤维细胞（MEF）中抑制FB1诱导凋亡的基因。一种杆状病毒基因，凋亡抑制因子（CpIAP），可保护这些细胞免于凋亡。CpIAP可阻断肿瘤坏死因子（TNF）途径以及其他机制诱导的凋亡。对TNF信号转导途径参与FB1诱导凋亡的进一步支持是半胱天冬酶8的裂解。杆状病毒基因（斜体）p35对半胱天冬酶的抑制也抑制了FB1诱导的凋亡。FB1诱导凋亡不需要肿瘤抑制基因p53，因为p53-/-MEF在FB1处理后会发生凋亡。此外，Bcl-2在CV-1细胞或p53+/+MEF中不是FB1诱导凋亡的有效抑制剂。总之，这些结果提供了新的信息，有助于理解FB1诱导凋亡的机制。
