Triglyceride induces DNA damage leading to monocyte death by activating caspase-2 and caspase-8

被引：5

作者：

Jung, Byung Chul ^{[1
,2
]}

Kim, Hyun-Kyung ^{[2
,3
]}

Kim, Sung Hoon ^{[2
,4
]}

Kim, Yoon Suk ^{[2
]}

机构：

[1] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA

[2] Yonsei Univ, Coll Software & Digital Healthcare Convergence, Dept Biomed Lab Sci, Wonju 26493, South Korea

[3] Gimcheon Univ, Coll Nat Sci, Dept Biomed Lab Sci, Gimcheon 39528, South Korea

[4] Korea Nazarene Univ, Dept Biomed Lab Sci, Cheonan 31172, South Korea

来源：

BMB REPORTS | 2023年 / 56卷 / 03期

基金：

新加坡国家研究基金会;

关键词：

CELL-DEATH; OXIDATIVE STRESS; APOPTOSIS; TRIACYLGLYCEROLS; CHOLESTEROL; MACROPHAGES;

D O I：

10.5483/BMBRep.2022-0201

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Monocytes are peripheral leukocytes that function in innate immunity. Excessive triglyceride (TG) accumulation causes monocyte death and thus can compromise innate immunity. However, the mechanisms by which TG mediates monocyte death remain unclear to date. Thus, this study aimed to elucidate the mechanisms by which TG induces monocyte death. Results showed that TG induced monocyte death by activating caspase-3/7 and promoting poly (ADP-ribose) polymerase (PARP) cleavage. In addition, TG induced DNA damage and activated the ataxia telangiectasia mutated (ATM)/checkpoint kinase 2 and ATM-and Rad3-related (ATR)/checkpoint kinase 1 pathways, leading to the cell death. Furthermore, TG-induced DNA dam-age and monocyte death were mediated by caspase-2 and-8, and caspase-8 acted as an upstream molecule of caspase-2. Taken together, these results suggest that TG-induced monocyte death is mediated via the caspase-8/caspase-2/DNA damage/ executioner caspase/PARP pathways. [BMB Reports 2023; 56(3): 166-171]

引用

页码：166 / 171

页数：6

共 39 条

[1] Mechanism underlying oxidative stress-mediated lipotoxicity: Exposure of J774.2 macrophages to triacylglycerols facilitates mitochondrial reactive oxygen species production and cellular necrosis [J].

Aronis, A ;

Madar, Z ;

Tirosh, O .

FREE RADICAL BIOLOGY AND MEDICINE, 2005, 38 (09) :1221-1230

[2] A Dual Role of Caspase-8 in Triggering and Sensing Proliferation-Associated DNA Damage, a Key Determinant of Liver Cancer Development [J].

Boege, Yannick ;

Malehmir, Mohsen ;

Healy, Marc E. ;

Bettermann, Kira ;

Lorentzen, Anna ;

Vucur, Mihael ;

Ahuja, Akshay K. ;

Bohm, Friederike ;

Mertens, Joachim C. ;

Shimizu, Yutaka ;

Frick, Lukas ;

Remouchamps, Caroline ;

Mutreja, Karun ;

Kaehne, Thilo ;

Sundaravinayagam, Devakumar ;

Wolf, Monika J. ;

Rehrauer, Hubert ;

Koppe, Christiane ;

Speicher, Tobias ;

Padrissa-Altes, Susagna ;

Maire, Renaud ;

Schattenberg, Jo Rn M. ;

Jeong, Ju-Seong ;

Liu, Lei ;

Zwirner, Stefan ;

Boger, Regina ;

Hueser, Norbert ;

Davis, Roger J. ;

Mullhaupt, Beat ;

Moch, Holger ;

Schulze-Bergkamen, Henning ;

Clavien, Pierre-Alain ;

Werner, Sabine ;

Borsig, Lubor ;

Luther, Sanjiv A. ;

Jost, Philipp J. ;

Weinlich, Ricardo ;

Unger, Kristian ;

Behrens, Axel ;

Hillert, Laura ;

Dillon, Christopher ;

Di Virgilio, Michela ;

Wallach, David ;

Dejardin, Emmanuel ;

Zender, Lars ;

Naumann, Michael ;

Walczak, Henning ;

Green, Douglas R. ;

Lopes, Massimo ;

Lavrik, Inna .

CANCER CELL, 2017, 32 (03) :342-+

[3] Caspase-2 regulates S-phase cell cycle events to protect from DNA damage accumulation independent of apoptosis (vol 41, pg 204, 2022) [J].

Boice, Ashley G. ;

Lopez, Karla E. ;

Pandita, Raj K. ;

Parsons, Melissa J. ;

Charendoff, Chloe I. ;

Charaka, Vijay ;

Carisey, Alexandre F. ;

Pandita, Tej K. ;

Bouchier-Hayes, Lisa .

ONCOGENE, 2022, 41 (29) :3732-3734

[4] Caspase-2: the orphan caspase [J].

Bouchier-Hayes, L. ;

Green, D. R. .

CELL DEATH AND DIFFERENTIATION, 2012, 19 (01) :51-57

[5] The role of caspase-2 in stress-induced apoptosis [J].

Bouchier-Hayes, Lisa .

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2010, 14 (06) :1212-1224

[6] Role of monocytes and macrophages in regulating immune response following lung transplantation [J].

Chiu, Stephen ;

Bharat, Ankit .

CURRENT OPINION IN ORGAN TRANSPLANTATION, 2016, 21 (03) :239-245

[7] ATR: an essential regulator of genome integrity [J].

Cimprich, Karlene A. ;

Cortez, David .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2008, 9 (08) :616-627

[8]

Da JJ, 2015, INT J CLIN EXP PATHO, V8, P10625

[9] Evaluation of DNA damage in Wistar rat tissues with hyperlipidemia induced by tyloxapol [J].

de Sousa, Joubert Aires ;

Pereira, Patricia ;

Allgayer, Mariangela da Costa ;

Marroni, Norma Possa ;

Falcao Ferraz, Alexandre de Barros ;

Picada, Jaqueline Nascimento .

EXPERIMENTAL AND MOLECULAR PATHOLOGY, 2017, 103 (01) :51-55

[10] Determination of DNA damage induced by oxidative stress in hyperlipidemic patients [J].

Harangi, M ;

Remenyik, É ;

Seres, I ;

Varga, Z ;

Katona, E ;

Paragh, G .

MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS, 2002, 513 (1-2) :17-25

← 1 2 3 4 →