原创力文档targeting of mycobacterium tuberculosis heparin-binding hemagglutinin to mitochondria in macrophages针对结核分枝杆菌heparin-binding血凝素在巨噬细胞中线粒体.pdfVIP
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targeting of mycobacterium tuberculosis heparin-binding hemagglutinin to mitochondria in macrophages针对结核分枝杆菌heparin-binding血凝素在巨噬细胞中线粒体
Targeting of Mycobacterium tuberculosis Heparin-
Binding Hemagglutinin to Mitochondria in Macrophages
1. 1. 1 1 1 1
Hosung Sohn , Jong-Seok Kim , Sung Jae Shin , Kwangwook Kim , Choul-Jae Won , Woo Sik Kim , Ki-
1 1 2 1 1
Nam Min , Han-Gyu Choi , Je Chul Lee , Jeong-Kyu Park , Hwa-Jung Kim *
1 Department of Microbiology, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon, South Korea, 2 Department of
Microbiology, Kyungpook National University School of Medicine, Daegu, South Korea
Abstract
Mycobacterium tuberculosis heparin-binding hemagglutinin (HBHA), a virulence factor involved in extrapulmonary
dissemination and a strong diagnostic antigen against tuberculosis, is both surface-associated and secreted. The role of
HBHA in macrophages during M. tuberculosis infection, however, is less well known. Here, we show that recombinant HBHA
produced by Mycobacterium smegmatis effectively induces apoptosis in murine macrophages. DNA fragmentation, nuclear
condensation, caspase activation, and poly (ADP-ribose) polymerase cleavage were observed in apoptotic macrophages
treated with HBHA. Enhanced reactive oxygen species (ROS) production and Bax activation were essential for HBHA-induced
apoptosis, as evidenced by a restoration of the viability of macrophages pretreated with N-acetylcysteine, a potent ROS
scavenger, or transfected with Bax siRNA. HBHA is targeted to the mitochondrial compartment of HBHA-treated and M.
tuberculosis-infected macrophages. Dissipation of the mitochondrial t
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