Endoplasmic reticulum stress response is involved in Mycobacterium tuberculosis protein ESAT-6-mediated apoptosis.
Mycobacterium tuberculosis (Mtb) infection leads to the induction of the apoptotic response, which is associated with bacilli killing. The early secreted mycobacterial antigen ESAT-6 of Mtb has been shown to induce apoptosis in human macrophages and epithelial cells. In the present study, we demonstrate that the stimulation of human epithelial A549 cells by ESAT-6 induces the endoplasmic reticulum (ER) stress response. We observed that ESAT-6 treatment increases intracellular Ca(2+) concentration, which results in ROS accumulation, and therefore induces the onset of ER stress-induced apoptosis. Our results uncover a novel apoptotic mechanism of ESAT-6 through ER stress responses in pathologic conditions such as tuberculosis.
Choi
Hong-Hee
HH
Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, South Korea.
Shin
Dong-Min
DM
Kang
Gun
G
Kim
Ki-Hye
KH
Park
Jin Bong
JB
Hur
Gang Min
GM
Lee
Hye-Mi
HM
Lim
Yun-Ji
YJ
Park
Jeong-Kyu
JK
Jo
Eun-Kyeong
EK
Song
Chang-Hwa
CH
D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism*; D017209:Apoptosis; D001426:Bacterial Proteins / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014376:Tuberculosis / Q000378:metabolism
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D011506:Proteins; D017382:Reactive Oxygen Species