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M. Brockhaus

Bio: M. Brockhaus is an academic researcher. The author has contributed to research in topics: Oxidative stress & Glutathione. The author has an hindex of 3, co-authored 3 publications receiving 380 citations.

Papers
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Journal ArticleDOI
TL;DR: It is demonstrated that exposure of cells to 50 μg/L HgCl2 for 30 min induces a 30% reduction in cellular glutathione (GSH) levels, and results indicate that mercury may play a role in pathophysiological mechanisms of AD.
Abstract: Concentrations of heavy metals, including mercury, have been shown to be altered in the brain and body fluids of Alzheimer's disease (AD) patients. To explore potential pathophysiological mechanisms we used an in vitro model system (SHSY5Y neuroblastoma cells) and investigated the effects of inorganic mercury (HgCl2) on oxidative stress, cell cytotoxicity, beta-amyloid production, and tau phosphorylation. We demonstrated that exposure of cells to 50 microg/L (180 nM) HgCl2 for 30 min induces a 30% reduction in cellular glutathione (GSH) levels (n = 13, p<0.001). Preincubation of cells for 30 min with 1 microM melatonin or premixing melatonin and HgCl2 appeared to protect cells from the mercury-induced GSH loss. Similarly, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assays revealed that 50 microg/L HgCl2 for 24 h produced a 50% inhibition of MTT reduction (n = 9, p<0.001). Again, melatonin preincubation protected cells from the deleterious effects of mercury, resulting in MTT reduction equaling control levels. The release of beta-amyloid peptide (Abeta) 1-40 and 1-42 into cell culture supernatants after exposure to HgCl2 was shown to be different: Abeta 1-40 showed maximal (15.3 ng/ml) release after 4 h, whereas Abeta 1-42 showed maximal (9.3 ng/ml) release after 6 h of exposure to mercury compared with untreated controls (n = 9, p<0.001). Preincubation of cells with melatonin resulted in an attenuation of Abeta 1-40 and Abeta 1-42 release. Tau phosphorylation was significantly increased in the presence of mercury (n = 9, p<0.001), whereas melatonin preincubation reduced the phosphorylation to control values. These results indicate that mercury may play a role in pathophysiological mechanisms of AD.

201 citations

Journal ArticleDOI
TL;DR: It is shown that β-estradiol exerts its neuroprotective action through mechanisms which reduce oxidative stress and reduce β-amyloid secretion, and contributes to a better understanding of the mode of action of estrogen with relevance to its use in the treatment of neurodegenerative disorders.

103 citations

Journal ArticleDOI
TL;DR: The results show that H2O2, UV light, Aβ1–42 and toxic Aβ25–35, but not the inactive Aβ35–25, produce a significant induction of oxidative stress and cell cytotoxicity.
Abstract: Redox changes within neurones are increasingly being implicated as an important causative agent in brain ageing and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD) Cells have developed a number of defensive mechanisms to maintain intracellular redox homeostasis, including the glutathione (GSH) system and antioxidant enzymes Here we examine the effects of N-acetyl-L-cysteine (NAC) on beta-amyloid (A beta) secretion and tau phosphorylation in SHSY5Y neuroblastoma cells after exposure to oxidative stress inducing/cytotoxic compounds (H(2)O(2), UV light and toxic A beta peptides) A beta and tau protein are hallmark molecules in the pathology of AD while the stress factors are implicated in the aetiology of AD The results show that H(2)O(2), UV light, A beta 1-42 and toxic A beta 25-35, but not the inactive A beta 35-25, produce a significant induction of oxidative stress and cell cytotoxicity The effects are reversed when cells are pre-treated with 30 mM NAC Cells exposed to H(2)O(2), UV light and A beta 25-35, but not A beta 35-25, secrete significantly higher amounts of A beta 1-40 and A beta 1-42 into the culture medium NAC pre-treatment increased the release of A beta 1-40 compared with controls and potentiated the release of both A beta 1-40 and A beta 1-42 in A beta 25-35-treated cells Tau phosphorylation was markedly reduced by H(2)O(2) and UV light but increased by A beta 25-35 NAC strongly lowered phospho-tau levels in the presence or absence of stress treatment

102 citations


Cited by
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Journal ArticleDOI
TL;DR: The three modern "faces" of mercury are the authors' perceptions of risk from the exposure of billions of people to methyl mercury in fish, mercury vapor from amalgam tooth fillings, and ethyl mercury in the form of thimerosal added as an antiseptic to widely used vaccines.
Abstract: The three modern "faces" of mercury are our perceptions of risk from the exposure of billions of people to methyl mercury in fish, mercury vapor from amalgam tooth fillings, and ethyl mercury in the form of thimerosal added as an antiseptic to widely used vaccines. In this article I review human exposure to and the toxicology of each of these three species of mercury. Mechanisms of action are discussed where possible. Key gaps in our current knowledge are identified from the points of view both of risk assessment and of mechanisms of action.

975 citations

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TL;DR: Decreased performance in areas of motor function and memory has been reported among children exposed to presumably safe mercury levels and disruption of attention, fine motorfunction and verbal memory was also found in adults on exposure to low mercury levels.

963 citations

Journal ArticleDOI
TL;DR: D diagnosis of mercury toxicity can be challenging but can be obtained with reasonable reliability and effective therapies for clinical toxicity have been described.
Abstract: Mercury is a toxic heavy metal which is widely dispersed in nature. Most human exposure results from fish consumption or dental amalgam. Mercury occurs in several chemical forms, with complex pharmacokinetics. Mercury is capable of inducing a wide range of clinical presentations. Diagnosis of mercury toxicity can be challenging but can be obtained with reasonable reliability. Effective therapies for clinical toxicity have been described.

791 citations

Journal ArticleDOI
TL;DR: Gender differences in susceptibility at lower exposure are uncertain, but recent data indicate that cadmium has estrogenic effects and affect female offspring, and experimental data suggest that females are more susceptible to immunotoxic effects of lead.

599 citations

Journal ArticleDOI

568 citations