Oxidative stress induces autophagic cell death independent of apoptosis in transformed and cancer cells

Chen, Yongqiang; McMillan-Ward, Eileen M.; Kong, Jiming; Israels, Sara J.; Gibson, Spencer B.

doi:10.1038/sj.cdd.4402233

Cited by 626 publications

(495 citation statements)

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“…Again, the loss of the cellular synthesis ability at 24 h was manifested under all the studied conditions. Autophagy triggered by oxidative stress has been amply documented in transformed and cancer cells (Chen et al, 2008), although the relationship between psychological and/ or physical stress and autophagy is still unknown. Recently, our group showed that autophagy may be directly related to the oxidative stress status of the muscle cells in beef (García-Macia et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Effect of animal mixing as a stressor on biomarkers of autophagy and oxidative stress during pig muscle maturation

Rubio-González

Potes

Illán-Rodríguez

et al. 2015

Animal

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The objective of this work was to study the postmortem evolution of potential biomarkers of autophagy (Beclin 1, LC3-II/LC3-I ratio) and oxidative stress (total antioxidant activity, TAA; superoxide dismutase activity, SOD and catalase activity, CAT) in the Longissimus dorsi muscle of entire male ((Large White × Landrace) × Duroc) pigs subjected to different management treatments that may promote stress, such as mixing unfamiliar animals at the farm and/or during transport and lairage before slaughter. During the rearing period at the farm, five animals were never mixed after the initial formation of the experimental groups (unmixed group at the farm, UF), whereas 10 animals were subjected to a common routine of being mixed with unfamiliar animals (mixed group at the farm, MF). Furthermore, two different treatments were used during the transport and lairage before slaughter: 10 pigs were not mixed (unmixed group during transport and lairage, UTL), whereas five pigs were mixed with unfamiliar animals on the lorry and during lairage (mixed group during transport and lairage, MTL). These mixing treatments were then combined into three pre-slaughter treatments -namely, UF-UTL, MF-UTL and MF-MTL. The results show that MF-UTL and MF-MTL increased significantly the muscle antioxidant defense (TAA, SOD and CAT) at short postmortem times (4 and 8 h; P < 0.001), followed by an earlier depletion of the antioxidant activity at 24 h postmortem (P < 0.05). We also found that mixing unfamiliar animals, both at the farm and during transport and lairage, triggers postmortem muscle autophagy, which showed an earlier activation (higher expression of Beclin 1 and LC3-II/LC3-I ratio at 4 h postmortem followed by a decreasing pattern of this ratio along first 24 h postmortem) in the muscle tissues of animals from the MF-UTL and MF-MTL groups, as an adaptive strategy of the muscle cells for counteracting induced stress. From these results, we propose that monitoring the evolution of the main biomarkers of autophagy (Beclin 1, LC3-II/LC3-I ratio) and muscle antioxidant defense (TAA, SOD, CAT) in the muscle tissue within the first 24 h postmortem may help the detection of animal stress and its potential effect on the postmortem muscle metabolism.

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Section: Discussionmentioning

confidence: 99%

Effect of animal mixing as a stressor on biomarkers of autophagy and oxidative stress during pig muscle maturation

Rubio-González

Potes

Illán-Rodríguez

et al. 2015

Animal

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“…Autophagy clears depolarized mitochondria to reduce the excessive production of ROS by increasing BECN1 or regulating ATG4 activity [26,27] , which is protective in MS.…”

Section: Autophagy and Mitochondria In Msmentioning

confidence: 99%

“…In MS, the decreased expression of cytochrome c oxidase subunit 5b may impair the function of mitochondria [24] . Dysfunction of mitochondria produces reactive oxygen species (ROS), which contribute to demyelination and axonal loss [25] .Autophagy clears depolarized mitochondria to reduce the excessive production of ROS by increasing BECN1 or regulating ATG4 activity [26,27] , which is protective in MS. …”

mentioning

confidence: 99%

Role of autophagy in the pathogenesis of multiple sclerosis

Liang

2015

Neurosci. Bull.

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Autophagy plays an important role in maintaining the cellular homeostasis. One of its functions is to degrade unnecessary organelles and proteins for energy recycling or amino-acids for cell survival. Ablation of autophagy leads to neurodegeneration. Multiple sclerosis (MS), a permanent neurological impairment typical of chronic inflammatory demyelinating disorder, is an auto-immune disease of the central nervous system (CNS). Autophagy is tightly linked to the innate and adaptive immune systems during the autoimmune process, and several studies have shown that autophagy directly participates in the progress of MS or experimental autoimmune encephalomyelitis (EAE, a mouse model of MS). Dysfunction of mitochondria that intensively infl uences the autophagy pathway is one of the important factors in the pathogenesis of MS. Autophagy-related gene (ATG) 5 and immune-related GTPase M (IRGM) 1 are increased, while ATG16L2 is decreased, in T-cells in EAE and active relapsing-remitting MS brains. Administration of rapamycin, an inhibitor of mammalian target of rapamycin ( mTOR), ameliorates relapsing-remitting EAE. Infl ammation and oxidative stress are increased in MS lesions and EAE, but Lamp2 and the LC3-II/LC3-I ratio are decreased. Furthermore, autophagy in various glial cells plays important roles in regulating neuro-infl ammation in the CNS, implying potential roles in MS. In this review, we discuss the role of autophagy in the peripheral immune system and the CNS in neuroinfl ammation associated with the pathogenesis of MS. Keywords: autophagy; multiple sclerosis; neuro-infl ammation ·Review· IntroductionAutophagy, a lysosome-dependent degradation pathway, contributes to maintaining cellular homeostasis. Clearance of long-lived proteins, unnecessary organelles, and aggregate-prone proteins is mainly executed by autophagy for recycling cellular materials [1] . There are three subtypes of autophagy, macroautophagy, chaperone-mediated autophagy (CMA), and mitophagy. Macroautophagy is the major type for selective degradation of protein aggregates or misfolded proteins. The ubiquitin-labeled proteins are recognized by autophagy receptors, such as p62, neighbor of BRCA1 gene 1 (NBR1), and NIP3-like protein X (NIX), to form autophagosomes that then fuse with lysosomes for degradation. Many autophagy-related genes function during this process, such as Unc51-like kinase (ULK1) and autophagy-related gene (ATG) 5. Mammalian target of rapamycin (mTOR) represses autophagy by regulating ULK1 phosphorylation, while AMPK activates this process.CMA mediates the degradation of large molecular-weight proteins containing the KFERQ motif recognized by heat shock cognate protein of 70 kDa (HSC70). The substrate is then escorted to lysosome-associated membrane protein 2 (LAMP2A) for lysosomal degradation. Mitophagy is responsible for the degradation of damaged mitochondria.Parkin and PINK1 play critical roles in this process [2] . More Neurosci Bull August 1, 2015, 31(4): 435-444 436 attention has been paid to autophagy in the path...

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“…36 ROS are associated with different types of cell death mechanisms (classical apoptosis, necrosis and autophagy). [38][39][40][41][42][43] CD40 stimulation induced an almost twofold increase in basal ROS production when compared with unstimulated CLL cells. (Figures 6a and b left panel, 3T40 medium versus 3T3 medium).…”

Section: Rituximab-mediated Death Of Cd40-stimulated Cll Cells Is Ca mentioning

confidence: 99%

CD40 stimulation sensitizes CLL cells to rituximab-induced cell death

et al. 2011

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In vitro CD40-stimulated chronic lymphocytic leukemia (CLL) cells are resistant to cytotoxic drugs. In sharp contrast, we here show that CD40 stimulation sensitizes CLL cells to rituximabmediated cell death. This increased sensitivity is specific for anti-CD20 treatment. Rituximab-mediated death in CD40-stimulated CLL cells shows rapid kinetics (within hours), and is caspase and p53 independent, but depends on extracellular Ca 2 þ and reactive oxygen species (ROS) production. By increasing basal ROS production, CD40 stimulation sensitizes CLL cells to rituximab-mediated death. Our findings provide a rationale for combination treatment of CLL with cytotoxic drugs and anti-CD20 monoclonal antibodies.

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Oxidative stress induces autophagic cell death independent of apoptosis in transformed and cancer cells

Cited by 626 publications

References 38 publications

Effect of animal mixing as a stressor on biomarkers of autophagy and oxidative stress during pig muscle maturation

Effect of animal mixing as a stressor on biomarkers of autophagy and oxidative stress during pig muscle maturation

Role of autophagy in the pathogenesis of multiple sclerosis

CD40 stimulation sensitizes CLL cells to rituximab-induced cell death

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