Isocitrate dehydrogenase 2 deficiency induces endothelial inflammation via p66sh-mediated mitochondrial oxidative stress

Jeon, Byeong Hwa; Piao, Shuyu; Nagar, Harsha; Jung, Sungyup; Kim, Seonhee; Lee, Ikjun; Kim, Sung‐Min; Song, Hee‐Jung; Shin, Nara; Kim, Dong Ho; Irani, Kaikobad; Park, Jeen‐Woo; Kim, Cuk-Seong

doi:10.1016/j.bbrc.2018.07.117

Cited by 15 publications

(15 citation statements)

References 27 publications

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“…Taking endothelial cells for example, a representative mechanism that links to sterile inflammation is the so-called senescence associated secretory phenotype (SASP) ( Tchkonia et al, 2013 ). It has been shown that upon mitochondrial dysfunction, endothelial cells secrete multiple pro-inflammatory cytokines includes interleukin (IL)-1, IL-6, and TNF-α, and upregulate intercellular adhesion molecule-1 (ICAM-1) expression which attracts monocyte activation and adhesion ( Choi et al, 2018 ). Indeed, our recent unpublished data have also revealed that Trx2-deletion induced mitochondrial dysfunction also lead to endothelial cell senescence and SASP in vivo and in vitro , which might further recruit innate immune cells to augment inflammatory responses.…”

Section: Mitochondrial Function and Rosmentioning

confidence: 99%

Mitochondria, Oxidative Stress and Innate Immunity

2018

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Canonical functions of mitochondria include the regulation of cellular survival, orchestration of anabolic and metabolic pathways, as well as reactive oxygen species (ROS) signaling. Recent discoveries, nevertheless, have demonstrated that mitochondria are also critical elements to stimulate innate immune signaling cascade that is able to intensify the inflammation upon cytotoxic stimuli beyond microbial infection. Here we review the expanding research field of mitochondria and oxidative stress in innate immune system to highlight the new mechanistic insights and discuss the pathological relevance of mitochondrial dysregulation induced aberrant innate immune responses in a growing list of sterile inflammatory diseases.

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Section: Mitochondrial Function and Rosmentioning

confidence: 99%

Mitochondria, Oxidative Stress and Innate Immunity

2018

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“…In addition to immune cells, mitochondrial dysfunctions can also extensively influence the function of non-immune cells. Indeed, as a result of mitochondrial dysfunction, endothelial cells secrete multiple pro-inflammatory cytokines such as IL-1, IL-6, and tumor necrosis factor-alpha (TNF-α), and upregulate intercellular adhesion molecule-1 (ICAM-1) expression, which attracts monocyte activation and adhesion, leading to a sterile inflammation called senescence associated secretory phenotype (SASP) [ 132 , 133 ].…”

Section: Dna Damage Inducersmentioning

confidence: 99%

DNA Damage Response and Immune Defense

Nastasi

Mannarino

D’Incalci

2020

IJMS

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DNA damage is the cause of numerous human pathologies including cancer, premature aging, and chronic inflammatory conditions. The DNA damage response (DDR), in turn, coordinates DNA damage checkpoint activation and promotes the removal of DNA lesions. In recent years, several studies have shown how the DDR and the immune system are tightly connected, revealing an important crosstalk between the two of them. This interesting interplay has opened up new perspectives in clinical studies for immunological diseases as well as for cancer treatment. In this review, we provide an overview, from cellular to molecular pathways, on how DDR and the immune system communicate and share the crucial commitment of maintaining the genomic fitness.

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“…substrates of NADPH-producing malic enzyme and isocitrate dehydrogenase (IDH2, Fig. 2), the deficiency of which causes oxidative stress in ECs and vascular inflammation 92 . Indeed, NADPH is used to regenerate reduced glutathione (GSH) from its oxidized form (GSSG) by glutathione reductase (see below) 93 .…”

Section: Redox Metabolismmentioning

confidence: 99%

The metabolic engine of endothelial cells

et al. 2019

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Endothelial cells (ECs) line the quiescent vasculature, but can form new blood vessels (a process termed angiogenesis) in disease. Strategies targeting angiogenic growth factors have been clinically developed for the treatment of malignant and ocular diseases. Studies over the past decade documented that several pathways of central carbon metabolism are necessary for EC homeostasis and growth, and that strategies that stimulate or block EC metabolism can be used to respectively promote or inhibit vessel growth. In this review, we provide an updated oversight of our growing understanding of central carbon metabolic pathways in ECs and the therapeutic opportunities of targeting EC metabolism.

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Isocitrate dehydrogenase 2 deficiency induces endothelial inflammation via p66sh-mediated mitochondrial oxidative stress

Cited by 15 publications

References 27 publications

Mitochondria, Oxidative Stress and Innate Immunity

Mitochondria, Oxidative Stress and Innate Immunity

DNA Damage Response and Immune Defense

The metabolic engine of endothelial cells

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