Proteome analysis of mouse macrophages treated with anthrax lethal toxin.
Anthrax toxin produced by Bacillus anthracis is a tripartite toxin comprising of protective antigen (PA), lethal factor (LF) and edema factor (EF). PA is the receptor-binding component, which facilitates the entry of LF or EF into the cytosol. EF is a calmodulin-dependent adenylate cyclase that causes edema whereas LF is a zinc metalloprotease and leads to necrosis of macrophages. It is also important to note that the exact mechanism of LF action is still unclear. With this view in mind, in the present study, we investigated a proteome wide effect of anthrax lethal toxin (LT) on mouse macrophage cells (J774A.1). Proteome analysis of LT-treated and control macrophages revealed 41 differentially expressed protein spots, among which phosphoglycerate kinase I, enolase I, ATP synthase (beta subunit), tubulin beta2, gamma-actin, Hsp70, 14-3-3 zeta protein and tyrosine/tryptophan-3-monooxygenase were found to be down-regulated, while T-complex protein-1, vimentin, ERp29 and GRP78 were found to be up-regulated in the LT-treated macrophages. Analysis of up- and down-regulated proteins revealed that primarily the stress response and energy generation proteins play an important role in the LT-mediated macrophage cell death.
Chandra
Harish
H
Institute of Genomics and Integrative Biology, Mall Road, Delhi-110007, India.
Gupta
Pradeep K
PK
Sharma
Kirti
K
Mattoo
Abid R
AR
Garg
Satyendra K
SK
Gade
W N
WN
Sirdeshmukh
Ravi
R
Maithal
Kapil
K
Singh
Yogendra
Y
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000633:toxicity*; D001408:Bacillus anthracis / Q000737:chemistry* / Q000378:metabolism; D001427:Bacterial Toxins / Q000737:chemistry / Q000235:genetics / Q000633:toxicity*; D003599:Cytoskeleton / Q000378:metabolism; D015536:Down-Regulation; D004487:Edema / Q000276:immunology / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D004789:Enzyme Activation / Q000187:drug effects* / Q000502:physiology; D006360:Heat-Shock Proteins / Q000378:metabolism; D007928:Lethal Dose 50; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism; D051379:Mice; D020543:Proteome / Q000032:analysis* / Q000378:metabolism; D015854:Up-Regulation
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D020543:Proteome; C030325:anthrax toxin; D000255:Adenosine Triphosphate; D008666:Metalloendopeptidases