Mercuric chloride induces apoptosis via a mitochondrial-dependent pathway in human leukemia cells

Araragi, Saeko; Kondoh, Masuo; Kawase, Masaki; Saito, Sayaka; Higashimoto, Minoru; Sato, Masao

doi:10.1016/s0300-483x(02)00443-2

Cited by 57 publications

(36 citation statements)

References 50 publications

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“…This suggests that mercury being accumulated in nuclei could directly act on DNA, which is related to mercury's genotoxicity. The higher concentration of mercury in mitochondria may have a relationship with previous reports that mercury-induced apoptosis may occur via a mitochondria-dependent pathway in several cell lines (36 ).…”

Section: (12) G/l] (29 30 )mentioning

confidence: 51%

Increased Oxidative DNA Damage, as Assessed by Urinary 8-Hydroxy-2′-Deoxyguanosine Concentrations, and Serum Redox Status in Persons Exposed to Mercury

Chen

et al. 2005

Clinical Chemistry

115

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Background: Mercury is a ubiquitous and highly toxic environmental pollutant. In this study, we evaluated the relationship between mercury exposure and oxidative stress, serum and urinary mercury concentrations, oxidative DNA damage, and serum redox status in chronically mercury-exposed persons compared with healthy controls. Methods: We measured urinary 8-hydroxy-2-deoxyguanosine (8-OHdG), which we used as a biomarker of oxidative DNA damage in the mercury-exposed persons, by HPLC with electrochemical detection (ECD). We evaluated antioxidant status by measuring the activities of superoxide dismutase and glutathione peroxidase and the concentrations of total reduced glutathione and protein-bound thiols in serum. Results: The significant increase in 8-OHdG concentrations in urine indicated that mercury-induced oxidative damage to DNA occurred in vivo. Differences in body mercury burden and antioxidant enzyme activities were statistically significant between the mercury-exposed

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Section: (12) G/l] (29 30 )mentioning

confidence: 51%

Increased Oxidative DNA Damage, as Assessed by Urinary 8-Hydroxy-2′-Deoxyguanosine Concentrations, and Serum Redox Status in Persons Exposed to Mercury

Chen

et al. 2005

Clinical Chemistry

115

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“…Early studies showed that the damage induced by CCl 4 in liver is partly involved in the apoptosis pathway in vivo. At least 2 different apoptosis pathwaysthe mitochondrial pathway and the death-receptor pathway -lead to caspase activation [17] . Although past reports have disclosed caspase 3 activation and other histopathological changes in CCl 4 -induced apoptotic hepatocytes [10,12] , little is known about the precise molecular mechanisms of apoptosis induction.…”

Section: Discussionmentioning

confidence: 99%

Apoptosis initiated by carbon tetrachloride in mitochondria of rat primary cultured hepatocytes

Cai

Gong

et al. 2005

Acta Pharmacologica Sinica

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Aim: To investigate the mitochondria‐initiated apoptosis pathway involved in Carbon tetrachloride (CCl4) hepatotoxicity in vitro. Methods: Several cytotoxicity endpoints, including WST‐8 metabolism, lactate dehydrogenase leakage and morphological changes, were examined. The 5,5′‐dithio‐bis(2‐nitrobenzoic acid) reaction was used to measure reduced glutathione level, and the malondialdehyde level was determined using the thiobarbituric acid assay. The release of cytochrome c and Bcl‐XL was detected by Western blot. Caspase‐3 activity was measured using the fluorogenic substrate Ac‐DEVD‐AMC. DNA fragmentation was used to evaluate cell apoptosis. Results: A time‐and dose‐dependent decrease in cellular glutathione content was observed, along with a concomitant increase in malondialdehyde levels following the application of CCl4. Caspase 3 activity was stimulated at all doses of CCl4, with the most significant activation at 3 mmol/L. Cytochrome c was released obviously after CCl4 treatment. A time‐dependent decrease in Bcl‐XL expression was observed. DNA fragmentation results revealed apoptosis and necrosis following CCl4 treatment. Conclusion: Oxidative damage is one of the essential mechanisms of CCl4 hepatotoxicity, which triggers apoptosis via the mitochondria‐initiated pathway.

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“…It usually involves the reduction of mitochondrial transmembrane potential Dw m and the release of cytochrome c into the cytoplasm, followed by initiation of the apoptosis cascade, e.g., activation of caspase 3 Kluck et al 1997). Mercury is known to accumulate inside mitochondria, and thus it can change mitochondrial membrane permeability and cause reduction of Dw m (Araragi et al 2003;InSug et al 1997;Shenker et al 1999).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial viability and apoptosis induced by aluminum, mercuric mercury and methylmercury in cell lines of neural origin

Toimela

Tähti

2004

Arch Toxicol

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Mercury and aluminum are considered to be neurotoxic metals, and they are often connected with the onset of neurodegenerative diseases. In this study, mercuric mercury, methylmercury and aluminum were studied in three different cell lines of neural origin. To evaluate the effects, mitochondrial cytotoxicity and apoptosis induced by the metals were measured after various incubation times. SH-SY5Y neuroblastoma, U 373MG glioblastoma, and RPE D407 retinal pigment epithelial cells were subcultured to appropriate cell culture plates and 0.01-1,000 microM concentrations of methylmercury, mercuric and aluminum chloride were added into the growth medium. In the assay measuring the mitochondrial dehydrogenase activity, WST-1, the cultures were exposed for 15 min, 24 or 48 h before measurement. Cells were allowed to recover from the exposure in part of the study. Apoptosis induced by the metals was measured after 6-, 24- and 48-h exposure times with the determination of activated caspase 3 enzyme. Mitochondrial assays showed a clear dose-response and exposure time-response to the metals. The most toxic was methylmercury (EC50 ~0.8 microM, 48 h), and the most sensitive cell line was the neuroblastoma cell line SH-SY5Y. Furthermore, there was marked mitochondrial activation, especially in connection with aluminum and methylmercury at low concentrations. This activation may be important during the initiation of cellular processes. All the metals tested induced apoptosis, but with a different time-course and cell-line specificity. In microscopic photographs, glioblastoma cells formed fibrillary tangles, and neuroblastoma cells settled along the fibrilles in cocultures of glial and neuronal cell lines during aluminum exposure. The study emphasized the toxicity of methylmercury to neural cells and showed that aluminum alters various cellular activities.

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Mercuric chloride induces apoptosis via a mitochondrial-dependent pathway in human leukemia cells

Cited by 57 publications

References 50 publications

Increased Oxidative DNA Damage, as Assessed by Urinary 8-Hydroxy-2′-Deoxyguanosine Concentrations, and Serum Redox Status in Persons Exposed to Mercury

Increased Oxidative DNA Damage, as Assessed by Urinary 8-Hydroxy-2′-Deoxyguanosine Concentrations, and Serum Redox Status in Persons Exposed to Mercury

Apoptosis initiated by carbon tetrachloride in mitochondria of rat primary cultured hepatocytes

Mitochondrial viability and apoptosis induced by aluminum, mercuric mercury and methylmercury in cell lines of neural origin

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