Cadmium induces autophagy through ROS-dependent activation of the LKB1–AMPK signaling in skin epidermal cells

Son, Young-Ok; Wang, Xin; Hitron, John Andrew; Zhang, Zhuo; Cheng, Senping; Budhraja, Amit; Ding, Song‐Ze; Lee, Jeong-Chae; Shi, Xianglin

doi:10.1016/j.taap.2011.06.024

Cited by 120 publications

(82 citation statements)

References 57 publications

(73 reference statements)

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“…The mCherry-EGFP-LC3B plasmid was purchased from Addgene (Cambridge, MA), and GFP-LC3 plasmid has been described previously (18). shRNAs for knockdown of catalase and SOD2 were obtained from (OriGene Technologies, Inc., Rockville, MD).…”

Section: Methodsmentioning

confidence: 99%

Antioncogenic and Oncogenic Properties of Nrf2 in Arsenic-induced Carcinogenesis

Son

Pratheeshkumar

Roy

et al. 2015

Journal of Biological Chemistry

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Background: Arsenic induced cell transformation and carcinogenesis. Results: Arsenic-transformed cells have the property of apoptosis/autophagy resistance. Conclusion:The constitutive activation of Nrf2 in arsenic-transformed cells up-regulates antioxidants, decreases ROS generation, and causes apoptosis resistance and tumorigenesis. Significance: Antioncogenic role of inducible Nrf2 in normal cells and oncogenic role of constitutive activation of Nfr2 in cancer cells may increase our understanding of the mechanism of arsenic carcinogenesis and its prevention.

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Section: Methodsmentioning

confidence: 99%

Antioncogenic and Oncogenic Properties of Nrf2 in Arsenic-induced Carcinogenesis

Son

Pratheeshkumar

Roy

et al. 2015

Journal of Biological Chemistry

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“…However, cadmium toxicity has been linked to the activation of autophagy in human cells on the basis of the tumorigenic and cell death-inducing properties of this metal (68). The molecular mechanism by which Cd 2ϩ activates autophagic programs in human cells is unclear, although it may involve ROS formation (69)(70)(71). Cadmium has also been shown to induce autophagy in sea urchin embryos, but the underlying signaling pathway remains to be identified (72).…”

Section: Discussionmentioning

confidence: 99%

Activation of Autophagy by Metals in Chlamydomonas reinhardtii

et al. 2015

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Autophagy is an intracellular self-degradation pathway by which eukaryotic cells recycle their own material in response to specific stress conditions. Exposure to high concentrations of metals causes cell damage, although the effect of metal stress on autophagy has not been explored in photosynthetic organisms. In this study, we investigated the effect of metal excess on autophagy in the model unicellular green alga Chlamydomonas reinhardtii. We show in cells treated with nickel an upregulation of ATG8 that is independent of CRR1, a global regulator of copper signaling in Chlamydomonas. A similar effect on ATG8 was observed with copper and cobalt but not with cadmium or mercury ions. Transcriptome sequencing data revealed an increase in the abundance of the protein degradation machinery, including that responsible for autophagy, and a substantial overlap of that increased abundance with the hydrogen peroxide response in cells treated with nickel ions. Thus, our results indicate that metal stress triggers autophagy in Chlamydomonas and suggest that excess nickel may cause oxidative damage, which in turn activates degradative pathways, including autophagy, to clear impaired components and recover cellular homeostasis. Eukaryotic cells are able to degrade and recycle their own material when they are exposed to nutrient starvation or other adverse conditions through a catabolic pathway known as macroautophagy or autophagy. This process is characterized by the formation of double-membrane vesicles termed autophagosomes that engulf and deliver cytosolic components to the vacuole/lysosome for degradation (1-4). The primary function of autophagy is to recycle cytoplasmic material as well as to clear damaged organelles or toxic cellular components generated during stress in order to maintain cellular homeostasis. In higher eukaryotes, autophagy has also been implicated in cell differentiation, development and cell death, and several human pathologies, such as cancer and neurodegenerative diseases (5, 6).Autophagy is mediated by highly conserved autophagy-related (ATG) genes, which have been described in organisms ranging from yeasts to mammals. Some ATG proteins are required for the formation of the autophagosome and constitute the core autophagy machinery (4,7,8). This group of proteins includes the ATG8 and ATG12 ubiquitin-like systems required for vesicle expansion. The ATG8 protein has been widely used to monitor autophagy in many systems (9) because, unlike other ATG proteins, this protein firmly binds to the autophagosome membrane through a covalent bond to phosphatidylethanolamine (PE). Most of the core ATG proteins are conserved in land plants (10-12) and in evolutionarily distant algae, including freshwater species, such as the model green alga Chlamydomonas reinhardtii (herein referred to as Chlamydomonas) (13) and marine species (14). Our current knowledge about autophagy in algae is still limited compared to our knowledge about autophagy in other eukaryotes, but recent studies, mainly performed in Chlamydomon...

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“…mTOR kinase is a major negative regulator of autophagy. mTOR signaling is frequently dysregulated in cancer, where LKB1/AMPK signaling can act upstream of it [20]. Our data demonstrate that ω3-PUFAs override mTOR activation induced by IRI through autophagy activation in fat-1 mice.…”

Section: Discussionmentioning

confidence: 61%

Omega-3 polyunsaturated fatty acids protect against ischemia-reperfusion renal injury through AMPK-mediated autophagy

Dh¹,

Tw²,

J³

et al. 2017

Preprint

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Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI). ω3-Polyunsaturated fatty acids (ω3-PUFAs) show protective effects against various renal injuries. It was recently reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI) and evaluated associated mechanisms. C57Bl/6 background fat-1 mice and wild-type mice (wt) were divided into four groups: wt sham (n = 10), fat-1 sham (n = 10), wt IRI (reperfusion 35 min after clamping both the renal artery and vein; n = 15), and fat-1 IRI (n = 15). Kidneys and blood were harvested 24 h after IRI. Renal histological and molecular data were collected. The kidneys of fat-1 mice showed better renal cell survival, renal function, and pathological damage than those of wt mice after IRI. In addition, fat-1 mice showed less oxidative stress and autophagy impairment; greater amounts of LC3, Beclin-1, and Atg7; lower amounts of p62; and higher levels of renal cathepsin D and ATP6E than wt kidneys. They also showed more AMPK activation, which resulted in the inhibition of phosphorylation of the mammalian target of rapamycin (mTOR). Collectively, ω3-PUFAs in fat-1 mice contributed to AMPK mediated autophagy activation, leading to a renoprotective response.

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Cadmium induces autophagy through ROS-dependent activation of the LKB1–AMPK signaling in skin epidermal cells

Cited by 120 publications

References 57 publications

Antioncogenic and Oncogenic Properties of Nrf2 in Arsenic-induced Carcinogenesis

Antioncogenic and Oncogenic Properties of Nrf2 in Arsenic-induced Carcinogenesis

Activation of Autophagy by Metals in Chlamydomonas reinhardtii

Omega-3 polyunsaturated fatty acids protect against ischemia-reperfusion renal injury through AMPK-mediated autophagy

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