Toxic effects of cobalt in primary cultures of mouse astrocytes

Karovic, Olga; Tonazzini, Ilaria; Rebola, Nelson; Edström, Erik; Lövdahl, Cecilia; Fredholm, Bertil B.; Daré, Elisabetta

doi:10.1016/j.bcp.2006.11.008

Cited by 133 publications

(101 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These cobalt levels are much higher than those of plasma measured during human exposure to Co 2+ but almost identical to the concentrations used in other investigations of metabolism (Karovic et al, 2006). However, in a previous study we had demonstrated that, at lower concentrations -e.g., 5-15 m -Co 2+ inhibits ATP synthesis in a dose-dependent manner (Bragadin et al, 2007).…”

Section: Resultssupporting

confidence: 81%

“…This suggests that production of ROS induced by the metal acts directly on mitochondria to provoke the release of cytochrome c (cyt c) from external mitochondrial membrane, which leads to the activation of caspase 9 and to apoptosis (Pulido and Parrish, 2003). Similar conclusions have also been reported by other authors studying the toxic effects of cobalt in primary cultures of mouse astrocytes (Karovic et al, 2006). The interaction of Co 2+ with mitochondrial function has been preliminarily investigated at the level of ATP synthesis, with inhibition of this phenomenon, probably ascribable to the opening of the transition pore (Bragadin et al, 2007).…”

Section: Introductionsupporting

confidence: 78%

“…In a previous paper, it is reported that, over the concentration range of 0.2-0.8 mM, Co 2+ has toxic effects on primary cultures of mouse astrocytes (Karovic et al, 2006). These cobalt levels are much higher than those of plasma measured during human exposure to Co 2+ but almost identical to the concentrations used in other investigations of metabolism (Karovic et al, 2006).…”

Section: Resultsmentioning

confidence: 79%

“…Vitamin B 12 is necessary for the organism, because it is involved in the formation of some proteins and in the normal functionality of the nervous system. Its lack can cause pernicious anaemia and peripheral nervous system diseases (Karovic et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Cobalt induces oxidative stress in isolated liver mitochondria responsible for permeability transition and intrinsic apoptosis in hepatocyte primary cultures

Battaglia

Compagnone

Bandino

et al. 2009

The International Journal of Biochemistry & Cell Biology

100

View full text Add to dashboard Cite

a b s t r a c tIt is well established that cobalt mediates the occurrence of oxidative stress which contributes to cell toxicity and death. However, the mechanisms of these effects are not fully understood. This investigation aimed at establishing if cobalt acts as an inducer of mitochondrial-mediated apoptosis and at clarifying the mechanism of this process.Cobalt, in the ionized species Co 2+ , is able to induce the phenomenon of mitochondrial permeability transition (MPT) in rat liver mitochondria (RLM) with the opening of the transition pore. In fact, Co 2+ induces mitochondrial swelling, which is prevented by cyclosporin A and other typical MPT inhibitors such as Ca 2+ transport inhibitors and bongkrekic acid, as well as anti-oxidant agents. In parallel with mitochondrial swelling, Co 2+ also induces the collapse of electrical membrane potential. However in this case, cyclosporine A and the other MPT inhibitors (except ruthenium red and EGTA) only partially prevent « drop, suggesting that Co 2+ also has a proton leakage effect on the inner mitochondrial membrane. MPT induction is due to oxidative stress, as a result of generation by Co 2+ of the highly damaging hydroxyl radical, with the oxidation of sulfhydryl groups, glutathione and pyridine nucleotides. Co 2+ also induces the release of the pro-apoptotic factors, cytochrome c and AIF. Incubation of rat hepatocyte primary cultures with Co 2+ results in apoptosis induction with caspase activation and increased level of expression of HIF-1␣.All these observations allow us to state that, in the presence of calcium, Co 2+ is an inducer of apoptosis triggered by mitochondrial oxidative stress.

show abstract

Section: Resultssupporting

confidence: 81%

Section: Introductionsupporting

confidence: 78%

Section: Resultsmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cobalt induces oxidative stress in isolated liver mitochondria responsible for permeability transition and intrinsic apoptosis in hepatocyte primary cultures

Battaglia

Compagnone

Bandino

et al. 2009

The International Journal of Biochemistry & Cell Biology

100

View full text Add to dashboard Cite

show abstract

“…CoCl 2 stimulates the hypoxia responsive pathways and has been shown to induce apoptosis by mitochondrial pathways and hypoxia inducible factor 1 alpha (HIF-1α) dependent and independent mechanisms (Badr et al, 1999;Guo et al, 2006); its ability to stabilize HIF1α allows HIF1α to translocate into the nucleus and enhance transcription of hypoxia-responsive genes. Furthermore, cobalt is essential for vitamin B12 synthesis, but excess exposure can lead to toxicity and can induce apoptosis (Karovic et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Exacerbation of retinal degeneration in the absence of alpha crystallins in an in vivo model of chemically induced hypoxia

Yaung

Kannan

Wawrousek

et al. 2008

Experimental Eye Research

View full text Add to dashboard Cite

This study evaluated the role of crystallins in retinal degeneration induced by chemical hypoxia. Wild type, αA-crystallin (−/−), and αB-crystallin (−/−) mice received intravitreal injection of 12 nmol (low dose), 33 nmol (intermediate dose) or 60 nmol (high dose) cobalt chloride (CoCl 2 ). Hematoxylin and eosin and TdT-mediated dUTP nick-end labeling (TUNEL) stains were performed after 24 hours, 96 hours, and 1 week post-injection, while immunofluorescent stains for αA-and αB-crystallin were performed 1 week post-injection. The in vitro effects of CoCl 2 on αB-crystallin expression in ARPE-19 cells were determined by real time RT-PCR, Western blot, and confocal microscopy and studies evaluating subcellular distribution of αB-crystallin in the mitochondria and cytosol were also performed. Histologic studies revealed progressive retinal degeneration with CoCl 2 injection in wild type mice. Retinas of CoCl 2 injected mice showed transient increased expression of HIF-1α which was maximal 24 hours after injection. Intermediate dose CoCl 2 injection was associated with increased retinal immunofluorescence for both αA-and αB-crystallin; however, after high dose injection, increased retinal degeneration was associated with decreased levels of crystallin expression. Injection of CoCl 2 at either intermediate or high dose in αA-crystallin (−/−) and αB-crystallin (−/−) mice resulted in much more severe retinal degeneration compared to wild type eyes. A decrease in ARPE-19 total and cytosolic αB-crystallin expression with increasing CoCl2 treatment and an increase in mitochondrial αB-crystallin were found. We conclude that lack of α-crystallins accentuates retinal degeneration in chemically-induced hypoxia in vivo.

show abstract

Long-term Cognitive Trajectory After Total Joint Arthroplasty

et al. 2022

View full text Add to dashboard Cite

ImportanceIndividuals with total joint arthroplasty (TJA) have long-term exposure to metal-containing implants; however, whether long-term exposure to artificial implants is associated with cognitive function is unknown.ObjectiveTo compare long-term cognitive trajectories in individuals with and without TJA.Design, Setting, and ParticipantsThis population-based cohort study assessed serial cognitive evaluations of 5550 participants (≥50 years of age) from the Mayo Clinic Study of Aging between November 1, 2004, and December 31, 2020.ExposuresTotal joint arthroplasty of the hip or the knee.Main Outcomes and MeasuresLinear mixed-effects models were used to compare the annualized rate of change in global and domain-specific cognitive scores in participants with and without TJA, adjusting for age, sex, educational level, apolipoprotein E ε4 carrier status, and cognitive test practice effects.ResultsA total of 5550 participants (mean [SD] age at baseline, 73.04 [10.02] years; 2830 [51.0%] male) were evaluated. A total of 952 participants had undergone at least 1 TJA of the hip (THA, n = 430) or the knee (TKA, n = 626) before or after entry into the cohort. Participants with TJA were older, more likely to be female, and had a higher body mass index than participants without TJA. No difference was observed in the rate of cognitive decline in participants with and without TJA until 80 years of age. A slightly faster cognitive decline at 80 years or older and more than 8 years from surgery was observed (b = −0.03; 95% CI, −0.04 to −0.02). In stratified analyses by surgery type, the faster decline was observed primarily among older participants with TKA (b = −0.04; 95% CI, −0.06 to −0.02).Conclusions and RelevanceIn this cohort study, long-term cognitive trajectories in individuals with and without TJA were largely similar except for a slightly faster decline among the oldest patients with TKA; however, the magnitude of difference was small and of unknown clinical significance.

show abstract

Toxic effects of cobalt in primary cultures of mouse astrocytes

Cited by 133 publications

References 72 publications

Cobalt induces oxidative stress in isolated liver mitochondria responsible for permeability transition and intrinsic apoptosis in hepatocyte primary cultures

Cobalt induces oxidative stress in isolated liver mitochondria responsible for permeability transition and intrinsic apoptosis in hepatocyte primary cultures

Exacerbation of retinal degeneration in the absence of alpha crystallins in an in vivo model of chemically induced hypoxia

Long-term Cognitive Trajectory After Total Joint Arthroplasty

Contact Info

Product

Resources

About