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Cells
2012 Aug 27;13:597-616. doi: 10.3390/cells1030597.
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Heavy metals and metalloids as autophagy inducing agents: focus on cadmium and arsenic.
Chiarelli R
,
Roccheri MC
.
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In recent years, research on the autophagic process has greatly increased, invading the fields of biology and medicine. Several markers of the autophagic process have been discovered and various strategies have been reported studying this molecular process in different biological systems in both physiological and stress conditions. Furthermore, mechanisms of metalloid- or heavy metal-induced toxicity continue to be of interest given the ubiquitous nature and distribution of these contaminants in the environment where they often play the role of pollutants of numerous organisms. The aim of this review is a critical analysis and correlation of knowledge of autophagic mechanisms studied under stress for the most common arsenic (As) and cadmium (Cd) compounds. In this review we report data obtained in different experimental models for each compound, highlighting similarities and/or differences in the activation of autophagic processes. A more detailed discussion will concern the activation of autophagy in Cd-exposed sea urchin embryo since it is a suitable model system that is very sensitive to environmental stress, and Cd is one of the most studied heavy metal inductors of stress and modulator of different factors such as: protein kinase and phosphatase, caspases, mitochondria, heat shock proteins, metallothioneins, transcription factors, reactive oxygen species, apoptosis and autophagy.
Figure 1. Detection by immunofluorescence of LC3 protein on whole-mount embryos of sea urchin. Equatorial optical sections captured by confocal laser scanning microscopy. In green, LC3 protein detection; in red, nuclei stained with propidium iodide. (A) Control embryo, after 18 h of growth; (B) Cd-treated embryo for 18 h; (C) Control embryo, after 24 h of growth; (D) Cd-treated embryo for 24 h; (E, F) Enlargements of a section of (B, D), respectively. Bar = 50 μm.
Figure 2. Diagram showing an overview of the most representative cellular, biochemical, and molecular events activated as defense strategies in embryos and larvae of P.
lividus at different times post fertilization and various concentrations of CdCl2.
Achanzar,
Cadmium-induced malignant transformation of human prostate epithelial cells.
2001, Pubmed
Achanzar,
Cadmium-induced malignant transformation of human prostate epithelial cells.
2001,
Pubmed
Adastra,
A differential autophagic response to hyperglycemia in the developing murine embryo.
2011,
Pubmed
Agnello,
Apoptosis: Focus on sea urchin development.
2010,
Pubmed
,
Echinobase
Agnello,
Cadmium induces an apoptotic response in sea urchin embryos.
2007,
Pubmed
,
Echinobase
Apel,
Autophagy-A double-edged sword in oncology.
2009,
Pubmed
Arico,
The tumor suppressor PTEN positively regulates macroautophagy by inhibiting the phosphatidylinositol 3-kinase/protein kinase B pathway.
2001,
Pubmed
Azad,
Regulation of autophagy by reactive oxygen species (ROS): implications for cancer progression and treatment.
2009,
Pubmed
Bagchi,
Cadmium- and chromium-induced oxidative stress, DNA damage, and apoptotic cell death in cultured human chronic myelogenous leukemic K562 cells, promyelocytic leukemic HL-60 cells, and normal human peripheral blood mononuclear cells.
2000,
Pubmed
Bellodi,
Targeting autophagy potentiates tyrosine kinase inhibitor-induced cell death in Philadelphia chromosome-positive cells, including primary CML stem cells.
2009,
Pubmed
Bolt,
Arsenite exposure in human lymphoblastoid cell lines induces autophagy and coordinated induction of lysosomal genes.
2010,
Pubmed
Bolt,
Autophagy is the predominant process induced by arsenite in human lymphoblastoid cell lines.
2010,
Pubmed
Chargui,
Cadmium-induced autophagy in rat kidney: an early biomarker of subtoxic exposure.
2011,
Pubmed
Charoensuk,
Differential cytotoxic effects of arsenic compounds in human acute promyelocytic leukemia cells.
2009,
Pubmed
Cheng,
Protection against arsenic trioxide-induced autophagic cell death in U118 human glioma cells by use of lipoic acid.
2007,
Pubmed
Chiarelli,
Sea urchin embryos as a model system for studying autophagy induced by cadmium stress.
2011,
Pubmed
,
Echinobase
Chiu,
Combination treatment with arsenic trioxide and irradiation enhances cell-killing effects in human fibrosarcoma cells in vitro and in vivo through induction of both autophagy and apoptosis.
2010,
Pubmed
Chiu,
Combination treatment with arsenic trioxide and irradiation enhances autophagic effects in U118-MG cells through increased mitotic arrest and regulation of PI3K/Akt and ERK1/2 signaling pathways.
2009,
Pubmed
Choi,
Autophagy and cancer.
2012,
Pubmed
Chora,
Effect of cadmium in the clam Ruditapes decussatus assessed by proteomic analysis.
2009,
Pubmed
Crighton,
DRAM, a p53-induced modulator of autophagy, is critical for apoptosis.
2006,
Pubmed
Di Bartolomeo,
The role of autophagy during development in higher eukaryotes.
2010,
Pubmed
Di Gioacchino,
Autophagy as an ultrastructural marker of heavy metal toxicity in human cord blood hematopoietic stem cells.
2008,
Pubmed
Di Gioacchino,
Autophagy in hematopoietic stem/progenitor cells exposed to heavy metals: Biological implications and toxicological relevance.
2008,
Pubmed
Dong,
Promotion of autophagy and inhibition of apoptosis by low concentrations of cadmium in vascular endothelial cells.
2009,
Pubmed
Eisenberg-Lerner,
The paradox of autophagy and its implication in cancer etiology and therapy.
2009,
Pubmed
Filosto,
Environmentally relevant cadmium concentrations affect development and induce apoptosis of Paracentrotus lividus larvae cultured in vitro.
2008,
Pubmed
,
Echinobase
Gibson,
A matter of balance between life and death: targeting reactive oxygen species (ROS)-induced autophagy for cancer therapy.
2010,
Pubmed
Glienke,
Down-regulation of wt1 expression in leukemia cell lines as part of apoptotic effect in arsenic treatment using two compounds.
2006,
Pubmed
Gobe,
Mitochondria, reactive oxygen species and cadmium toxicity in the kidney.
2010,
Pubmed
Goussetis,
Autophagy is a critical mechanism for the induction of the antileukemic effects of arsenic trioxide.
2010,
Pubmed
Gozuacik,
Autophagy as a cell death and tumor suppressor mechanism.
2004,
Pubmed
Hamada,
Apoptosis induced by cadmium.
1997,
Pubmed
Hamdoun,
Embryo stability and vulnerability in an always changing world.
2007,
Pubmed
Han,
Tetraarsenic Hexoxide Induces Beclin-1-Induced Autophagic Cell Death as well as Caspase-Dependent Apoptosis in U937 Human Leukemic Cells.
2012,
Pubmed
Huang,
Sodium arsenite-induced DAPK promoter hypermethylation and autophagy via ERK1/2 phosphorylation in human uroepithelial cells.
2009,
Pubmed
Isakson,
Autophagy contributes to therapy-induced degradation of the PML/RARA oncoprotein.
2010,
Pubmed
Jha,
Genotoxic effects of sodium arsenite on human cells.
1992,
Pubmed
Joseph,
Mechanisms of cadmium carcinogenesis.
2009,
Pubmed
Kanzawa,
Arsenic trioxide induces autophagic cell death in malignant glioma cells by upregulation of mitochondrial cell death protein BNIP3.
2005,
Pubmed
Klionsky,
Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes.
2008,
Pubmed
Klionsky,
Guidelines for the use and interpretation of assays for monitoring autophagy.
2012,
Pubmed
Kroemer,
Autophagic cell death: the story of a misnomer.
2008,
Pubmed
Kroemer,
Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009.
2009,
Pubmed
Larson,
Beclin-1 expression in normal bladder and in Cd2+ and As3+ exposed and transformed human urothelial cells (UROtsa).
2010,
Pubmed
Liang,
Induction of autophagy and inhibition of tumorigenesis by beclin 1.
1999,
Pubmed
Lim,
Autophagy involvement in cadmium resistance through induction of multidrug resistance-associated protein and counterbalance of endoplasmic reticulum stress WI38 lung epithelial fibroblast cells.
2010,
Pubmed
Luo,
Apoptosis blocks Beclin 1-dependent autophagosome synthesis: an effect rescued by Bcl-xL.
2010,
Pubmed
Maiuri,
Functional and physical interaction between Bcl-X(L) and a BH3-like domain in Beclin-1.
2007,
Pubmed
Miller,
Molecular targets of arsenic trioxide in malignant cells.
2002,
Pubmed
Miller,
Mechanisms of action of arsenic trioxide.
2002,
Pubmed
Podgurskaya,
Cadmium concentration and subcellular distribution in organs of the mussel Crenomytilus grayanus from upwelling regions of Okhotsk Sea and Sea of Japan.
2006,
Pubmed
Qian,
Arsenic trioxide induces not only apoptosis but also autophagic cell death in leukemia cell lines via up-regulation of Beclin-1.
2007,
Pubmed
Qu,
Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene.
2003,
Pubmed
Raffoul,
SnoN/SkiL, a TGFβ signaling mediator: a participant in autophagy induced by arsenic trioxide.
2010,
Pubmed
Rainbow,
Kenneth Mellanby Review Award. Trace metal concentrations in aquatic invertebrates: why and so what?
2002,
Pubmed
Roccheri,
Cadmium induces the expression of specific stress proteins in sea urchin embryos.
2004,
Pubmed
,
Echinobase
Russo,
Stress to cadmium monitored by metallothionein gene induction in Paracentrotus lividus embryos.
2003,
Pubmed
,
Echinobase
Samali,
Heat shock proteins increase resistance to apoptosis.
1996,
Pubmed
Sansanwal,
Insights into novel cellular injury mechanisms by gene expression profiling in nephropathic cystinosis.
2010,
Pubmed
Sarbassov,
Growing roles for the mTOR pathway.
2005,
Pubmed
Scarlatti,
Does autophagy have a license to kill mammalian cells?
2009,
Pubmed
Scheifler,
Lead concentrations in feathers and blood of common blackbirds (Turdus merula) and in earthworms inhabiting unpolluted and moderately polluted urban areas.
2006,
Pubmed
Scherz-Shouval,
Oxidation as a post-translational modification that regulates autophagy.
2007,
Pubmed
Son,
Cadmium induces autophagy through ROS-dependent activation of the LKB1-AMPK signaling in skin epidermal cells.
2011,
Pubmed
Song,
Hypoxia-induced autophagy contributes to the chemoresistance of hepatocellular carcinoma cells.
2009,
Pubmed
Sturlan,
Docosahexaenoic acid enhances arsenic trioxide-mediated apoptosis in arsenic trioxide-resistant HL-60 cells.
2003,
Pubmed
Templeton,
Multiple roles of cadmium in cell death and survival.
2010,
Pubmed
Tice,
Effect of hepatic methyl donor status on urinary excretion and DNA damage in B6C3F1 mice treated with sodium arsenite.
1997,
Pubmed
Vacquier,
Laboratory on sea urchin fertilization.
2011,
Pubmed
,
Echinobase
Vazquez-Martin,
Autophagy facilitates the development of breast cancer resistance to the anti-HER2 monoclonal antibody trastuzumab.
2009,
Pubmed
Wang,
Cadmium-induced autophagy and apoptosis are mediated by a calcium signaling pathway.
2008,
Pubmed
Wang,
Cadmium toxicity toward autophagy through ROS-activated GSK-3beta in mesangial cells.
2009,
Pubmed
Xie,
Autophagosome formation: core machinery and adaptations.
2007,
Pubmed
Yang,
The cadmium-induced death of mesangial cells results in nephrotoxicity.
2009,
Pubmed
Yang,
Dynamic effects of autophagy on arsenic trioxide-induced death of human leukemia cell line HL60 cells.
2008,
Pubmed
Yu,
Autophagy and caspases: a new cell death program.
2004,
Pubmed
Yue,
Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor.
2003,
Pubmed
Zhu,
Apoptosis and growth inhibition in malignant lymphocytes after treatment with arsenic trioxide at clinically achievable concentrations.
1999,
Pubmed
