Toxic Metals and Autophagy

Abstract

The earth's resources are finite, and it can no longer be considered a source of inexhaustible bounty for the human population. However, this realization has not been able to contain the human desire for rapid industrialization. The collateral to overusing environmental resources is the high-level contamination of undesirable toxic metals, leading to bioaccumulation and cellular damage. Cytopathological features of biological systems represent a key variable in several diseases. A review of the literature revealed that autophagy (PCDII), a high-capacity process, may consist of selective elimination of vital organelles and/or proteins that intiate mechanisms of cytoprotection and homeostasis in different biological systems under normal physiological and stress conditions. However, the biological system does survive under various environmental stressors. Currently, there is no consensus that specifies a particular response as being a dependable biomarker of toxicology. Autophagy has been recorded as the initial response of a cell to a toxic metal in a concentration- and time-dependent manner. Various signaling pathways are triggered through cellular proteins and/or protein kinases that can lead to autophagy, apoptosis (or necroptosis), and necrosis. Although the role of autophagy in tumorigenesis is associated with promoting tumor cell survival and/or acting as a tumor suppressive mechanism, PCDII in metal-induced toxicity has not been extensively studied. The aim of this review is to analyze the comparative cytotoxicity of metals/metalloids and nanoparticles (As, Cd, Cr, Hg, Fe, and metal-NP) in cells enduring autophagy. It is noted that metals/metalloids and nanoparticles prefer ATG8/LC3 as a potent inducer of autophagy in several cell lines or animal cells. MAP kinases, death protein kinases, PI3K, AKT, mTOR, and AMP kinase have been found to be the major components of autophagy induction or inhibition in the context of cellular responses to metals/metalloids and nanoparticles.

Dysfunction of methionine sulfoxide reductases to repair damaged proteins by nickel nanoparticles

“…However, disrupted or blocked autophagy flux is considered to be upon exposure to nanomaterials [25]. For example, LC3 has been proposed to be a potent inducer of autophagy in response to metal-based NPs exposure, such as As, Cd, Cr, Hg and Fe [26]. In the present study, we observed that LC3 levels were inhibited by NiNPs and induced by C-NiNPs.…”

Autophagy as the effector and player in DNA damage response of cells to genotoxicants

“…The autophagy-related generelated 8 (ATG8/LC3) was shown to play a vital role in stimulating autophagy in response to metal toxicity. 9 Arsenic is a naturally existing pollutant worldwide, and can induce both an acute toxic effect and a late carcinogenic effect. Reactive oxygen species (ROS)-mediated oxidative damage, including oxidized lipids and oxidant-induced DNA damage, is a major cause of arsenic pathogenesis.…”

“…[9][10][11][12][13] Autophagy has been considered as the initial response of cells to metal toxicants, which may confer protection against cellular damage or act as a potential biomarker of toxic metals exposure. 9 Under metal treatment at a lethal toxic concentration, the induction of autophagy can provoke cell death either alone or in combination with an apoptotic pathway. The autophagy-related generelated 8 (ATG8/LC3) was shown to play a vital role in stimulating autophagy in response to metal toxicity.…”

Role of neurotoxicants and traumatic brain injury in α-synuclein protein misfolding and aggregation

“…It also serves as a cofactor for many proteins like hemoglobin and various enzymes [7]. However, disrupting Fe metabolism and homeostasis can lead to excessive Fe accumulation in the brain [16, 118] where it can stimulate α-Syn aggregation typically associated with P [46, 108]. Tyrosine fluorescence quenching shows only moderate binding of Fe (II) to α-Syn [52].…”