Hormesis: A stress response in cells exposed to low levels of heavy metals

Damelin, L. I. I.; Vokes, S.; Whitcutt, J.M.; Damelin, Steven B.; Alexander, J. J.

doi:10.1191/096032700678816133

Cited by 62 publications

(52 citation statements)

References 12 publications

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“…Of note, ATP synthesis was induced at lower compound concentrations in response to some compounds. This is an example of hormesis, which is associated with cellular stress [22]. Of note, there was clear evidence of hormesis in hESC-derived hepatocytes postexposure to valproic acid, felbamate, and dacarbazine.…”

Section: Discussionmentioning

confidence: 85%

Accurate Prediction of Drug-Induced Liver Injury Using Stem Cell-Derived Populations

Szkolnicka

Farnworth

Lucendo‐Villarin

et al. 2013

Stem Cells Translational Medicine

102

101

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It has been observed that there is an imperative to develop predictive human systems that more effectively study and/or prevent the onset of liver disease and decompensated organ function. A serum‐free, scalable, and shippable cell‐based model that faithfully predicts the potential for human liver injury has been developed. Such a resource has direct application in human modeling, and, in the future, could play an important role in developing renewable cell‐based therapies.

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Section: Discussionmentioning

confidence: 85%

Accurate Prediction of Drug-Induced Liver Injury Using Stem Cell-Derived Populations

Szkolnicka

Farnworth

Lucendo‐Villarin

et al. 2013

Stem Cells Translational Medicine

102

101

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“…Hormesis refers to a process whereby a sublethal stressor renders an organism resistant to subsequent stress. This effect has been demonstrated in multiple stress models, both in cell culture to in vivo human models, including studies on dietary restriction, exercise, radiation, chemical and heat exposures (Damelin et al 2000;Damelin and Alexander 2001;Cypser et al 2006;Mattson 2008;Le Bourg 2009). The mechanisms that mediate hormesis are ill defined; nevertheless, previous research has implicated members of the heat shock protein 70 (HSP70) family and metallothionein (MT) proteins as contributors to hormesis.…”

Section: Discussionmentioning

confidence: 98%

Hormetic Effects of Acute Methylmercury Exposure on GRP78 Expression in Rat Brain Cortex

Zhang

Liu

et al. 2012

Dose-Response

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ᮀ This study aims to explore the expression of GRP78, a marker of endoplasmic reticulum (ER) stress, in the cortex of rat brains acutely exposed to methylmercury (MeHg). Thirty Sprague-Dawley (SD) rats were randomly divided into six groups, and decapitated 6 hours (h) after intraperitoneal (i.p.) injection of MeHg (2, 4, 6, 8 or 10 mg/kg body weight) or normal saline. Protein and mRNA expression of Grp78 were detected by western blotting and real-time PCR, respectively. The results showed that a gradual increase in GRP78 protein expression was observed in the cortex of rats acutely exposed to MeHg (2, 4 or 6 mg/kg). Protein levels peaked in the 6 mg/kg group (p < 0.05 vs. controls), decreased in the 8 mg/kg group, and bottomed below the control level in the 10 mg/kg group. Parallel changes were noted for Grp78 mRNA expression. It may be implied that acute exposure to MeHg induced hormetic dose-dependent changes in Grp78 mRNA and protein expression, suggesting that activation of ER stress is involved in MeHg-induced neurotoxicity. Low level MeHg exposure may induce GRP78 protein expression to stimulate endogenous cytoprotective mechanisms.

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“…Determination of dose-response effects is general procedure in toxicology for risk evaluation and the establishment of exposure guidelines in view of monophasic responses. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay has been widely used toward this end and has also permitted to reveal in some cases biphasic hormesis responses (13,14,43,51). Hormesis has been defined as a dose-response relationship in which a stimulatory response occurs at low doses, and an inhibitory response takes place at high doses, resulting in a U-or inverted U-shaped dose response (10).…”

mentioning

confidence: 99%

Characterization of oxidized low-density lipoprotein-induced hormesis-like effects in osteoblastic cells

Hamel¹,

Abed²,

Brissette³

et al. 2008

American Journal of Physiology-Cell Physiology

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Hamel P, Abed E, Brissette L, Moreau R. Characterization of oxidized low-density lipoprotein-induced hormesis-like effects in osteoblastic cells. Am J Physiol Cell Physiol 294: C1021-C1033, 2008. First published February 20, 2008 doi:10.1152/ajpcell.00361.2007.-Epidemiological studies indicate that patients suffering from atherosclerosis are predisposed to develop osteoporosis. Atherogenic determinants such as oxidized low-density lipoprotein (oxLDL) particles have been shown both to stimulate the proliferation and promote apoptosis of bone-forming osteoblasts. Given such opposite responses, we characterized the oxLDL-induced hormesis-like effects in osteoblasts. Biphasic 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reductive activity responses were induced by oxLDL where low concentrations (10 -50 g/ml) increased and high concentrations (from 150 g/ml) reduced the MTT activity. Cell proliferation stimulation by oxLDL partially accounted for the increased MTT activity. No alteration of mitochondria mass was noticed, whereas low concentrations of oxLDL induced mitochondria hyperpolarization and increased the cellular levels of reactive oxygen species (ROS). The oxLDL-induced MTT activity was not related to intracellular ROS levels. OxLDL increased NAD(P)H-associated cellular fluorescence and flavoenzyme inhibitor diphenyleneiodonium reduced basal and oxLDL-induced MTT activity, suggesting an enhancement of NAD(P)H-dependent cellular reduction potential. Low concentrations of oxLDL reduced cellular thiol content and increased metallothionein expression, suggesting the induction of compensatory mechanisms for the maintenance of cell redox state. These concentrations of oxLDL reduced osteoblast alkaline phosphatase activity and cell migration. Our results indicate that oxLDL particles cause hormesis-like response with the stimulation of both proliferation and cellular NAD(P)H-dependent reduction potential by low concentrations, whereas high concentrations lead to reduction of MTT activity associated with the cell death. Given the effects of low concentrations of oxLDL on osteoblast functions, oxLDL may contribute to the impairment of bone remodeling equilibrium.osteoblasts; atherosclerosis; oxysterol ELEVATED LEVELS of serum low-density lipoprotein (LDL) particles are considered as the most important atherogenic risk factor. LDL particles are thought to become atherogenic after undergoing oxidative modifications, and key roles of oxidized LDL (various oxidized species collectively designated oxLDL) in atherosclerosis have been largely reviewed by Steinberg (46). OxLDL and oxysterols have been shown to increase or decrease proliferation and trigger the apoptosis process depending on the cell types related to vasculature alterations, nature of oxLDL and oxysterols, and on the concentrations used (52), thus supporting numerous deleterious effects that sustain the development of atherosclerosis. Also, a number of clinical studies suggest an association between cardiovascular disease and the develo...

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Hormesis: A stress response in cells exposed to low levels of heavy metals

Cited by 62 publications

References 12 publications

Accurate Prediction of Drug-Induced Liver Injury Using Stem Cell-Derived Populations

Accurate Prediction of Drug-Induced Liver Injury Using Stem Cell-Derived Populations

Hormetic Effects of Acute Methylmercury Exposure on GRP78 Expression in Rat Brain Cortex

Characterization of oxidized low-density lipoprotein-induced hormesis-like effects in osteoblastic cells

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