PMID- 30911956
OWN - NLM
STAT- MEDLINE
DCOM- 20190718
LR  - 20200225
IS  - 1573-4919 (Electronic)
IS  - 0300-8177 (Linking)
VI  - 457
IP  - 1-2
DP  - 2019 Jul
TI  - Early secreted antigenic target of 6-kDa of Mycobacterium tuberculosis promotes 
      caspase-9/caspase-3-mediated apoptosis in macrophages.
PG  - 179-189
LID - 10.1007/s11010-019-03522-x [doi]
AB  - Mycobacterium tuberculosis (Mtb) is an intracellular pathogen that triggers 
      several survival mechanisms against the host immune system. Many studies show 
      that the diverse components of Mtb can modulate apoptosis in various types of 
      cells differently. So far, apoptosis induced by ESAT-6, an early secreted 
      antigenic target of 6-kDa of Mtb, has been studied but the details of molecular 
      mechanism and signaling pathway remain incompletely defined. This study 
      investigated the role of recombinant ESAT-6 in inducing apoptosis in primary bone 
      marrow-derived macrophages (BMDMs) of mice using Annexin V/PI assay with FACS 
      analysis and Western blotting technique. It has been found that ESAT-6-induced 
      apoptosis in BMDMs in a dose- and time-dependent pattern. Apoptosis induced by 
      ESAT-6 was mainly via the intrinsic pathway with elevated protein levels of 
      cleaved caspase-9 and -3. Furthermore, ESAT-6 also induced Bim activation during 
      this process. Interestingly, this event was TLR2-dependent since the effect of 
      ESAT-6 on apoptosis vanished in BMDM from mice with TLR2 deficiency. Furthermore, 
      ROS generation and MAPKs phosphorylation induced by ESAT-6 were also involved in 
      caspase-9 and caspase-3 activation. Taken together, these data suggest that 
      ESAT-6-mediated apoptosis is involved in ROS-MAPKs signaling and further 
      activating the intrinsic pathway, which provides new insights into the basic 
      physiology of macrophage death in tuberculosis.
FAU - Lin, Jiahui
AU  - Lin J
AD  - Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, School of 
      Medicine, Tongji University, 507 Zhengmin Road, Shanghai, 200433, China.
AD  - Department of Microbiology and Immunology, School of Medicine, Tongji University, 
      1239 Siping Road, Shanghai, 200092, China.
FAU - Chang, Qun
AU  - Chang Q
AD  - Department of Microbiology and Immunology, School of Medicine, Tongji University, 
      1239 Siping Road, Shanghai, 200092, China.
FAU - Dai, Xueting
AU  - Dai X
AD  - Department of Microbiology and Immunology, School of Medicine, Tongji University, 
      1239 Siping Road, Shanghai, 200092, China.
FAU - Liu, Dan
AU  - Liu D
AD  - Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, School of 
      Medicine, Tongji University, 507 Zhengmin Road, Shanghai, 200433, China.
AD  - Department of Microbiology and Immunology, School of Medicine, Tongji University, 
      1239 Siping Road, Shanghai, 200092, China.
FAU - Jiang, Yuyin
AU  - Jiang Y
AD  - Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, School of 
      Medicine, Tongji University, 507 Zhengmin Road, Shanghai, 200433, China.
AD  - Department of Microbiology and Immunology, School of Medicine, Tongji University, 
      1239 Siping Road, Shanghai, 200092, China.
FAU - Dai, Yalei
AU  - Dai Y
AD  - Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, School of 
      Medicine, Tongji University, 507 Zhengmin Road, Shanghai, 200433, China. 
      daiyl@tongji.edu.cn.
AD  - Department of Microbiology and Immunology, School of Medicine, Tongji University, 
      1239 Siping Road, Shanghai, 200092, China. daiyl@tongji.edu.cn.
LA  - eng
GR  - 81471562/The National Natural Science Foundation of China/
GR  - 2017YFA0505900/The National Key Research and Development Program of China/
PT  - Journal Article
DEP - 20190325
PL  - Netherlands
TA  - Mol Cell Biochem
JT  - Molecular and cellular biochemistry
JID - 0364456
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Bacterial Proteins)
RN  - 0 (ESAT-6 protein, Mycobacterium tuberculosis)
RN  - EC 3.4.22.- (Casp3 protein, mouse)
RN  - EC 3.4.22.- (Casp9 protein, mouse)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 9)
SB  - IM
MH  - Animals
MH  - Antigens, Bacterial/chemistry/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Bacterial Proteins/chemistry/*pharmacology
MH  - Bone Marrow Cells/metabolism/pathology
MH  - Caspase 3/*metabolism
MH  - Caspase 9/*metabolism
MH  - Macrophages/*metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mycobacterium tuberculosis/*chemistry
OTO - NOTNLM
OT  - Apoptosis
OT  - ESAT-6
OT  - MAPK
OT  - Macrophage
OT  - ROS
OT  - TLR2
EDAT- 2019/03/27 06:00
MHDA- 2019/07/19 06:00
CRDT- 2019/03/27 06:00
PHST- 2018/09/22 00:00 [received]
PHST- 2019/03/14 00:00 [accepted]
PHST- 2019/03/27 06:00 [pubmed]
PHST- 2019/07/19 06:00 [medline]
PHST- 2019/03/27 06:00 [entrez]
AID - 10.1007/s11010-019-03522-x [pii]
AID - 10.1007/s11010-019-03522-x [doi]
PST - ppublish
SO  - Mol Cell Biochem. 2019 Jul;457(1-2):179-189. doi: 10.1007/s11010-019-03522-x. 
      Epub 2019 Mar 25.