title: Proteome analysis of mouse macrophages treated with anthrax lethal toxin.
abstract: 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.
authors.affiliation: Institute of Genomics and Integrative Biology, Mall Road, Delhi-110007, India.
authors.forename: Harish
authors.initials: H
authors.lastname: Chandra
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Gupta
authors.forename: Kirti
authors.initials: K
authors.lastname: Sharma
authors.forename: Abid R
authors.initials: AR
authors.lastname: Mattoo
authors.forename: Satyendra K
authors.initials: SK
authors.lastname: Garg
authors.forename: W N
authors.initials: WN
authors.lastname: Gade
authors.forename: Ravi
authors.initials: R
authors.lastname: Sirdeshmukh
authors.forename: Kapil
authors.initials: K
authors.lastname: Maithal
authors.forename: Yogendra
authors.initials: Y
authors.lastname: Singh
mesh_terms: 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
chemical_list: 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