The roles of reactive oxygen species (ROS) and autophagy in the survival and death of leukemia cells

Chen, Yongfeng; Líu, Hao; Luo, Xin; Zhao, Zhiqiang; Zou, Zhenyou; Li, Jing; Lin, Xiaojing; Liang, Yong

doi:10.1016/j.critrevonc.2017.02.004

Cited by 95 publications

(69 citation statements)

References 114 publications

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“…The fourth major finding is that through modulation of transcription factors CREB and ATF4, TRPM2 regulates expression of ULK1, Atg7 and Atg5, significantly impacting autophagy. ROS induce autophagy, which eliminates damaged mitochondria and controls cellular ROS levels 48 . Autophagy is a pro-survival mechanism in hematopoietic disease and promotes resistance to chemotherapy 32 whereas blockade of autophagy increases chemotherapy sensitivity in AML 32,36 .…”

Section: Discussionmentioning

confidence: 99%

Transient receptor potential ion channel TRPM2 promotes AML proliferation and survival through modulation of mitochondrial function, ROS, and autophagy

et al. 2020

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Transient receptor potential melastatin 2 (TRPM2) ion channel has an essential function in maintaining cell survival following oxidant injury. Here, we show that TRPM2 is highly expressed in acute myeloid leukemia (AML). The role of TRPM2 in AML was studied following depletion with CRISPR/Cas9 technology in U937 cells. In in vitro experiments and in xenografts, depletion of TRPM2 in AML inhibited leukemia proliferation, and doxorubicin sensitivity was increased. Mitochondrial function including oxygen consumption rate and ATP production was reduced, impairing cellular bioenergetics. Mitochondrial membrane potential and mitochondrial calcium uptake were significantly decreased in depleted cells. Mitochondrial reactive oxygen species (ROS) were significantly increased, and Nrf2 was decreased, reducing the antioxidant response. In TRPM2-depleted cells, ULK1, Atg7, and Atg5 protein levels were decreased, leading to autophagy inhibition. Consistently, ATF4 and CREB, two master transcription factors for autophagosome biogenesis, were reduced in TRPM2-depleted cells. In addition, Atg13 and FIP200, which are known to stabilize ULK1 protein, were decreased. Reconstitution with TRPM2 fully restored proliferation, viability, and autophagy; ATF4 and CREB fully restored proliferation and viability but only partially restored autophagy. TRPM2 expression reduced the elevated ROS found in depleted cells. These data show that TRPM2 has an important role in AML proliferation and survival through regulation of key transcription factors and target genes involved in mitochondrial function, bioenergetics, the antioxidant response, and autophagy. Targeting TRPM2 may represent a novel therapeutic approach to inhibit myeloid leukemia growth and enhance susceptibility to chemotherapeutic agents through multiple pathways.

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Section: Discussionmentioning

confidence: 99%

Transient receptor potential ion channel TRPM2 promotes AML proliferation and survival through modulation of mitochondrial function, ROS, and autophagy

et al. 2020

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“…Thus, autophagy contributes to reduce the risk of formation of toxic protein aggregates [1] and promotes cell survival [2,3]. This catabolic process can be activated under various stress conditions such as oxidative stress [4], thermal stress [5, endoplasmic reticulum stress [6], hypoxia [7], and unbalanced diet [8]. In pathological situations including infection and cancer and neurodegenerative, cardiovascular, and autoimmune diseases, the roles of autophagy have been well demonstrated [9,[10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Signs of ROS-Associated Autophagy in Testis and Sperm in a Rat Model of Varicocele

Sadeghi

Erfani-Majd

Tavalaee

et al. 2020

Oxidative Medicine and Cellular Longevity

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Since autophagy was suspected to occur in the pathological situation of varicocele (VCL), we have attempted to confirm it here using a surgical model of varicocele-induced rats. Thirty Wistar rats were divided into three groups (varicocele/sham/control) and analyzed two months after the induction of varicocele. Testicular tissue sections and epididymal mature sperm were then monitored for classic features of varicocele, including disturbance of spermatogenesis, impaired testicular carbohydrate and lipid homeostasis, decreased sperm count, increased sperm nuclear immaturity and DNA damage, oxidative stress, and lipid peroxidation. At the same time, we evaluated the Atg7 protein content and LC3-II/LC3-1 protein ratio in testis and mature sperm cells, two typical markers of early and late cellular autophagy, respectively. We report here that testis and mature sperm show higher signs of autophagy in the varicocele group than in the control and sham groups, probably to try to mitigate the consequences of VCL on the testis and germ cells.

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“…Reactive oxygen species (ROS) are generated as a consequence of metabolic reactions in the mitochondria of cells. ROS with normal content, as a medium of energy transfer, are necessary for certain cellular activities, including signal transduction, enzyme activation and gene expression . However, when the cellular redox homeostasis is lost, oxidative stress is generated, altering and damaging intracellular biological molecules, including DNA, lipids, and proteins .…”

Section: Introductionmentioning

confidence: 99%

“…ROS with normal content, as a medium of energy transfer, are necessary for certain cellular activities, including signal transduction, enzyme activation and gene expression. [1][2][3] However, when the cellular redox homeostasis is lost, oxidative stress is generated, altering and damaging intracellular biological molecules, including DNA, lipids, and proteins. [4][5][6] Therefore, it is considered that oxidative stress is the origin of a wide variety of diseases, such as aging, 7 Alzheimer, 8 Parkinson, 9 cardiovascular disease, 10 diabetes, 11 and cancer.…”

Section: Introductionmentioning

confidence: 99%

Effect of magnesium on reducing the UV‐induced oxidative damage in marrow mesenchymal stem cells

Chen

Xiong

Zhao

et al. 2019

J Biomedical Materials Res

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Oxidative stress could cause damage to lipids, proteins and DNA, which is induced by the imbalance between the production of reactive oxygen species (ROS) and the biological system ability to counteract or detoxify their harmful effects. The oxidative stress damage significantly contributes to a number of diseases. Magnesium (Mg) is endowed with a novel function of removing excess ROS by releasing H2 during the degradation. In this study, in order to explore the property of anti‐oxidative damage of Mg metal, rat bone marrow mesenchymal stem cells (MSCs) oxidative damaged by ultraviolet (UV) radiation was employed to co‐culture with Mg metal. The effect of Mg metal on the response of antioxidant enzymes and mitochondria in MSCs was studied. We found that Mg metal could reduce the cellular oxidative stress damage and elevate the activities of antioxidant enzymes to maintain redox homeostasis. In addition, Mg metal could reduce the risk of UV‐induced cell apoptosis by increasing the ratio of Bcl‐2/Bax, elevating the mitochondrial membrane potential and blocking the release of cytochrome c. This finding showed Mg metal might have the potential for treating diseases caused by oxidative stress damage. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1253–1263, 2019.

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The roles of reactive oxygen species (ROS) and autophagy in the survival and death of leukemia cells

Cited by 95 publications

References 114 publications

Transient receptor potential ion channel TRPM2 promotes AML proliferation and survival through modulation of mitochondrial function, ROS, and autophagy

Transient receptor potential ion channel TRPM2 promotes AML proliferation and survival through modulation of mitochondrial function, ROS, and autophagy

Signs of ROS-Associated Autophagy in Testis and Sperm in a Rat Model of Varicocele

Effect of magnesium on reducing the UV‐induced oxidative damage in marrow mesenchymal stem cells

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