Association of p38/MAPK pathway on Bacillus anthracis lethal toxin suppressed erythrocytic differentiation

• Main Authors: Chang-yu Chen, 陳昌煜
• Other Authors: Der-shan Sun
• Format: Others
• Language: zh-TW
• Online Access: http://ndltd.ncl.edu.tw/handle/98468113245870638113

碩士 === 慈濟大學 === 分子生物暨人類遺傳學研究所 === 97 === Anthrax, a disease caused by Bacillus anthracis infection, usually coincides with hypoxic tissue damages, anemia and lethality and the mechanism associated with its high mortality is not yet clear. Anthrax lethal toxin (LT) is the major virulence factor produced by Bacillus anthracis, which that composed of two proteins: protective antigen (PA) and lethal factor (LF). PA binds to toxin receptors on the surfaces of target cells and allows entry of LF into the cytosol. LF is a zinc-dependent metalloprotease that cleaves the N-terminus of mitogen-activated protein kinase kinase (MKKs/MEKs), and thus disrupts the mitogen-activated protein kinase (MAPK) pathways: the ERK (extracellular signal-regulated kinase), p38 and JNK (c-Jun N-terminal kinase). Since anemia and hypoxic tissue damages are involved in anthrax-mediated mortality, these observations prompt us to analyze whether LT could block erythroid differentiation. Based on our data, we found that LT pretreatments could block GTP induced erythrocytic differentiation of K562 cells. In this study, we characterized the signaling pathway of LT suppressed erythrocytic differentiation by Western blotting. Our results suggest that LT might suppress erythrocytic differentiation through blocking p38 pathway.