Protochlamydia Induces Apoptosis of Human HEp-2 Cells through Mitochondrial Dysfunction Mediated by Chlamydial Protease-Like Activity Factor

Matsuo, Junji; Nakamura, Shinji; Ito, Atsushi; Yamazaki, Tomohiro; Ishida, Kasumi; Hayashi, Yasuhiro; Yoshida, Mitsutaka; Takahashi, Kaori; Sekizuka, Tsuyoshi; Takeuchi, Fumihiko; Kuroda, Makoto; Nagai, Hiroki; Hayashida, Kyoko; Sugimoto, Chihiro; Yamaguchi, Hiroyuki

Protochlamydia Induces Apoptosis of Human HEp-2 Cells through Mitochondrial Dysfunction Mediated by Chlamydial Protease-Like Activity Factor

Matsuo, Junji; Nakamura, Shinji; Ito, Atsushi et al.

PLoS One, 2013, 8(2), e56005

Permalink : https://hdl.handle.net/2115/52262

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アクセス権	open access
URI	https://hdl.handle.net/2115/52262
タイトル	Protochlamydia Induces Apoptosis of Human HEp-2 Cells through Mitochondrial Dysfunction Mediated by Chlamydial Protease-Like Activity Factor
著者	Matsuo, Junji ; Nakamura, Shinji ; Ito, Atsushi ; Yamazaki, Tomohiro ; Ishida, Kasumi ; Hayashi, Yasuhiro ; Yoshida, Mitsutaka ; Takahashi, Kaori ; Sekizuka, Tsuyoshi ; Takeuchi, Fumihiko ; Kuroda, Makoto ; Nagai, Hiroki ; Hayashida, Kyoko ; Sugimoto, Chihiro ; Yamaguchi, Hiroyuki
e-Rad_Researcher 50359486 著者名 Matsuo, Junji
e-Rad_Researcher 40207882 著者名 Nakamura, Shinji
著者名 Ito, Atsushi
著者名 Yamazaki, Tomohiro
著者名 Ishida, Kasumi
e-Rad_Researcher 30548178 著者名 Hayashi, Yasuhiro
著者名 Yoshida, Mitsutaka
著者名 Takahashi, Kaori
著者名 Sekizuka, Tsuyoshi
著者名 Takeuchi, Fumihiko
著者名 Kuroda, Makoto
著者名 Nagai, Hiroki
著者名 Hayashida, Kyoko
e-Rad_Researcher 90231373 著者名 Sugimoto, Chihiro
e-Rad_Researcher 40221650 著者名 Yamaguchi, Hiroyuki
言語	英語
発行日	2013-02-11
出版者	Public Library of Science
収録物名	PLoS One
巻(号)	8(2)
ページ	e56005
抄録	Obligate amoebal endosymbiotic bacterium Protochlamydia with ancestral pathogenic chlamydial features evolved to survive within protist hosts, such as Acanthamoba, 0.7-1.4 billion years ago, but not within vertebrates including humans. This observation raises the possibility that interactions between Protochlamydia and human cells may result in a novel cytopathic effect, leading to new insights into host-parasite relationships. Previously, we reported that Protochlamydia induces apoptosis of the immortalized human cell line, HEp-2. In this study, we attempted to elucidate the molecular mechanism underlying this apoptosis. We first confirmed that, upon stimulation with the bacteria, poly (ADP-ribose) polymerase (PARP) was cleaved at an early stage in HEp-2 cells, which was dependent on the amount of bacteria. A pan-caspase inhibitor and both caspase-3 and -9 inhibitors similarly inhibited the apoptosis of HEp-2 cells. A decrease of the mitochondrial membrane potential was also confirmed. Furthermore, lactacystin, an inhibitor of chlamydial protease-like activity factor (CPAF), blocked the apoptosis. Cytochalasin D also inhibited the apoptosis, which was dependent on the drug concentration, indicating that bacterial entry into cells was required to induce apoptosis. Interestingly, Yersinia type III inhibitors (ME0052, ME0053, and ME0054) did not have any effect on the apoptosis. We also confirmed that the Protochlamydia used in this study possessed a homologue of the cpaf gene and that two critical residues, histidine-101 and serine-499 of C. trachomatis CPAF in the active center, were conserved. Thus, our results indicate that after entry, Protochlamydia-secreted CPAF induces mitochondrial dysfunction with a decrease of the membrane potential, followed by caspase-9, caspase-3 and PARP cleavages for apoptosis. More interestingly, because C. trachomatis infection can block the apoptosis, our finding implies unique features of CPAF between pathogenic and primitive chlamydiae.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 3.0 Unported
PISSN	1932-6203
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1371/journal.pone.0056005