Roles of mitochondria-generated reactive oxygen species on X-ray-induced apoptosis in a human hepatocellular carcinoma cell line, HLE

Hiroko P. Indo; Osamu Inanami; Tomoko Koumura; Shigeaki Suenaga; Hsiu Chuan Yen; Shizuko Kakinuma; Ken Ichiro Matsumoto; Ikuo Nakanishi; William St Clair; Daret K. St Clair; Hirofumi Matsui; Richard Cornette; Oleg Gusev; Takashi Okuda; Yasuhito Nakagawa; Toshihiko Ozawa; Hideyuki J. Majima

doi:10.3109/10715762.2012.698012

Roles of mitochondria-generated reactive oxygen species on X-ray-induced apoptosis in a human hepatocellular carcinoma cell line, HLE

Hiroko P. Indo, Osamu Inanami, Tomoko Koumura, Shigeaki Suenaga, Hsiu Chuan Yen, Shizuko Kakinuma, Ken Ichiro Matsumoto, Ikuo Nakanishi, William St Clair, Daret K. St Clair, Hirofumi Matsui, Richard Cornette, Oleg Gusev, Takashi Okuda, Yasuhito Nakagawa, Toshihiko Ozawa, Hideyuki J. Majima

Research output: Contribution to journal › Review article › peer-review

48 Scopus citations

Abstract

HLE, a human hepatocellular carcinoma cell line was transiently transfected with normal human MnSOD and MnSOD without a mitochondrial targeting signal (MTS). Mitochondrial reactive oxygen species (ROS), lipid peroxidation and apoptosis were examined as a function of time following 18.8 Gy X-ray irradiation. Our results showed that the level of mitochondrial ROS increased and reached a maximum level 2 hours after X-ray irradiation. Authentic MnSOD, but not MnSOD lacking MTS, protected against mitochondrial ROS, lipid peroxidation and apoptosis. In addition, the levels of mitochondrial ROS were consistently found to always correlate with the levels of authentic MnSOD in mitochondria. These results suggest that only when MnSOD is located in mitochondria is it efficient in protecting against cellular injuries by X-ray irradiation and that mitochondria are the critical sites of X-ray-induced cellular oxidative injuries.

Original language	English
Pages (from-to)	1029-1043
Number of pages	15
Journal	Free Radical Research
Volume	46
Issue number	8
DOIs	https://doi.org/10.3109/10715762.2012.698012
State	Published - Aug 2012

Bibliographical note

Funding Information:
The authors declare no competing financial interest. This work was supported by a Grant-in-Aid for Scientific Research (C) (No. 22592093 to H.J.M, No. 23590064 to IN) and the Strategic Promotion Program for Basic Nuclear Research (to H.J.M.) of the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Program for Promotion of Basic and Applied Researches for Innovations in Bio-oriented Industry (BRAIN) (to H.J.M.) by the Ministry of Agriculture, Forestry and Fisheries of Japan.

Funding

The authors declare no competing financial interest. This work was supported by a Grant-in-Aid for Scientific Research (C) (No. 22592093 to H.J.M, No. 23590064 to IN) and the Strategic Promotion Program for Basic Nuclear Research (to H.J.M.) of the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Program for Promotion of Basic and Applied Researches for Innovations in Bio-oriented Industry (BRAIN) (to H.J.M.) by the Ministry of Agriculture, Forestry and Fisheries of Japan.

Funders	Funder number
Strategic Promotion Program for Basic Nuclear Research
National Childhood Cancer Registry – National Cancer Institute	R01CA143428
Japan Society for the Promotion of Science	22592094, 23590064, 22592093, 23592774, 24659551
Ministry of Education, Culture, Sports, Science and Technology
Japan Ministry of Agriculture, Forestry and Fisheries

Keywords

Apoptosis
Mitochondria
MnSOD
ROS
X-rays

ASJC Scopus subject areas

Biochemistry

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10.3109/10715762.2012.698012

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Indo, H. P., Inanami, O., Koumura, T., Suenaga, S., Yen, H. C., Kakinuma, S., Matsumoto, K. I., Nakanishi, I., St Clair, W., St Clair, D. K., Matsui, H., Cornette, R., Gusev, O., Okuda, T., Nakagawa, Y., Ozawa, T., & Majima, H. J. (2012). Roles of mitochondria-generated reactive oxygen species on X-ray-induced apoptosis in a human hepatocellular carcinoma cell line, HLE. Free Radical Research, 46(8), 1029-1043. https://doi.org/10.3109/10715762.2012.698012

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title = "Roles of mitochondria-generated reactive oxygen species on X-ray-induced apoptosis in a human hepatocellular carcinoma cell line, HLE",

abstract = "HLE, a human hepatocellular carcinoma cell line was transiently transfected with normal human MnSOD and MnSOD without a mitochondrial targeting signal (MTS). Mitochondrial reactive oxygen species (ROS), lipid peroxidation and apoptosis were examined as a function of time following 18.8 Gy X-ray irradiation. Our results showed that the level of mitochondrial ROS increased and reached a maximum level 2 hours after X-ray irradiation. Authentic MnSOD, but not MnSOD lacking MTS, protected against mitochondrial ROS, lipid peroxidation and apoptosis. In addition, the levels of mitochondrial ROS were consistently found to always correlate with the levels of authentic MnSOD in mitochondria. These results suggest that only when MnSOD is located in mitochondria is it efficient in protecting against cellular injuries by X-ray irradiation and that mitochondria are the critical sites of X-ray-induced cellular oxidative injuries.",

keywords = "Apoptosis, Mitochondria, MnSOD, ROS, X-rays",

author = "Indo, {Hiroko P.} and Osamu Inanami and Tomoko Koumura and Shigeaki Suenaga and Yen, {Hsiu Chuan} and Shizuko Kakinuma and Matsumoto, {Ken Ichiro} and Ikuo Nakanishi and {St Clair}, William and {St Clair}, {Daret K.} and Hirofumi Matsui and Richard Cornette and Oleg Gusev and Takashi Okuda and Yasuhito Nakagawa and Toshihiko Ozawa and Majima, {Hideyuki J.}",

note = "Funding Information: The authors declare no competing financial interest. This work was supported by a Grant-in-Aid for Scientific Research (C) (No. 22592093 to H.J.M, No. 23590064 to IN) and the Strategic Promotion Program for Basic Nuclear Research (to H.J.M.) of the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Program for Promotion of Basic and Applied Researches for Innovations in Bio-oriented Industry (BRAIN) (to H.J.M.) by the Ministry of Agriculture, Forestry and Fisheries of Japan.",

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Indo, HP, Inanami, O, Koumura, T, Suenaga, S, Yen, HC, Kakinuma, S, Matsumoto, KI, Nakanishi, I, St Clair, W, St Clair, DK, Matsui, H, Cornette, R, Gusev, O, Okuda, T, Nakagawa, Y, Ozawa, T & Majima, HJ 2012, 'Roles of mitochondria-generated reactive oxygen species on X-ray-induced apoptosis in a human hepatocellular carcinoma cell line, HLE', Free Radical Research, vol. 46, no. 8, pp. 1029-1043. https://doi.org/10.3109/10715762.2012.698012

TY - JOUR

T1 - Roles of mitochondria-generated reactive oxygen species on X-ray-induced apoptosis in a human hepatocellular carcinoma cell line, HLE

AU - Indo, Hiroko P.

AU - Inanami, Osamu

AU - Koumura, Tomoko

AU - Suenaga, Shigeaki

AU - Yen, Hsiu Chuan

AU - Kakinuma, Shizuko

AU - Matsumoto, Ken Ichiro

AU - Nakanishi, Ikuo

AU - St Clair, William

AU - St Clair, Daret K.

AU - Matsui, Hirofumi

AU - Cornette, Richard

AU - Gusev, Oleg

AU - Okuda, Takashi

AU - Nakagawa, Yasuhito

AU - Ozawa, Toshihiko

AU - Majima, Hideyuki J.

N1 - Funding Information: The authors declare no competing financial interest. This work was supported by a Grant-in-Aid for Scientific Research (C) (No. 22592093 to H.J.M, No. 23590064 to IN) and the Strategic Promotion Program for Basic Nuclear Research (to H.J.M.) of the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Program for Promotion of Basic and Applied Researches for Innovations in Bio-oriented Industry (BRAIN) (to H.J.M.) by the Ministry of Agriculture, Forestry and Fisheries of Japan.

PY - 2012/8

Y1 - 2012/8

N2 - HLE, a human hepatocellular carcinoma cell line was transiently transfected with normal human MnSOD and MnSOD without a mitochondrial targeting signal (MTS). Mitochondrial reactive oxygen species (ROS), lipid peroxidation and apoptosis were examined as a function of time following 18.8 Gy X-ray irradiation. Our results showed that the level of mitochondrial ROS increased and reached a maximum level 2 hours after X-ray irradiation. Authentic MnSOD, but not MnSOD lacking MTS, protected against mitochondrial ROS, lipid peroxidation and apoptosis. In addition, the levels of mitochondrial ROS were consistently found to always correlate with the levels of authentic MnSOD in mitochondria. These results suggest that only when MnSOD is located in mitochondria is it efficient in protecting against cellular injuries by X-ray irradiation and that mitochondria are the critical sites of X-ray-induced cellular oxidative injuries.

AB - HLE, a human hepatocellular carcinoma cell line was transiently transfected with normal human MnSOD and MnSOD without a mitochondrial targeting signal (MTS). Mitochondrial reactive oxygen species (ROS), lipid peroxidation and apoptosis were examined as a function of time following 18.8 Gy X-ray irradiation. Our results showed that the level of mitochondrial ROS increased and reached a maximum level 2 hours after X-ray irradiation. Authentic MnSOD, but not MnSOD lacking MTS, protected against mitochondrial ROS, lipid peroxidation and apoptosis. In addition, the levels of mitochondrial ROS were consistently found to always correlate with the levels of authentic MnSOD in mitochondria. These results suggest that only when MnSOD is located in mitochondria is it efficient in protecting against cellular injuries by X-ray irradiation and that mitochondria are the critical sites of X-ray-induced cellular oxidative injuries.

KW - Apoptosis

KW - Mitochondria

KW - MnSOD

KW - ROS

KW - X-rays

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U2 - 10.3109/10715762.2012.698012

DO - 10.3109/10715762.2012.698012

M3 - Review article

C2 - 22656864

AN - SCOPUS:84863906015

SN - 1071-5762

VL - 46

SP - 1029

EP - 1043

JO - Free Radical Research

JF - Free Radical Research

IS - 8

ER -

Roles of mitochondria-generated reactive oxygen species on X-ray-induced apoptosis in a human hepatocellular carcinoma cell line, HLE

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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