Regulation of cell death: the calcium–apoptosis link

Orrenius, Sten; Zhivotovsky, Boris; Nicotera, Pierluigi

doi:10.1038/nrm1150

Cited by 2,633 publications

(2,185 citation statements)

References 135 publications

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“…HgCI 2 exposure did not lead to an activation of caspase-3 in these cells. Visualization of apoptotic bodies, as a result of condensation with blebbing of the plasma membrane and subsequent membrane-enclosed fragments [42), confirmed these findings. However, none of the compounds resulted in a caspase-3 activation in the astrocytes.…”

Section: Ccf-sttglsupporting

confidence: 56%

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Toxicity of organic and inorganic mercury species in differentiated human neurons and human astrocytes

Lohren

Blagojevic

Fitkau

et al. 2015

Journal of Trace Elements in Medicine and Biology

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a b s t r a c tOrganic mercury (Hg) species exert their toxicity primarily in the central nervous system. The food relevant Hg species methylmercury (MeHg) has been frequently studied regarding its neurotoxic effects in vitro and in vivo. Neurotoxicity of thiomersal, which is used as a preservative in medical preparations, is to date less characterised. Due to dealkylation of organic Hg or oxidation of elemental Hg, inorganic Hg is present in the brain albeit these species are not able to readily cross the blood brain barrier. This study compared for the first time toxic effects of organic MeHg chloride (MeHgCl) and thiomersal as well as inorganic mercury chloride (HgCl 2 ) in differentiated human neurons (LUHMES) and human astrocytes (CCF-STTG1). The three Hg species differ in their degree and mechanism of toxicity in those two types of brain cells. Generally, neurons are more susceptible to Hg species induced cytotoxicity as compared to astrocytes. This might be due to the massive cellular mercury uptake in the differentiated neurons. The organic compounds exerted stronger cytotoxic effects as compared to inorganic HgCl 2 . In contrast to HgCl 2 exposure, organic Hg compounds seem to induce the apoptotic cascade in neurons following low-level exposure. No indicators for apoptosis were identified for both inorganic and organic mercury species in astrocytes. Our studies clearly demonstrate species-specific toxic mechanisms. A mixed exposure towards all Hg species in the brain can be assumed. Thus, prospectively coexposure studies as well as cocultures of neurons and astrocytes could provide additional information in the investigation of Hg induced neurotoxicity.

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Section: Ccf-sttglsupporting

confidence: 56%

“…Apoptosis is characterized by cell shrinkage, nuclear and cytoplasmic condensation and intracellular decomposition processes maintaining plasma membrane integrity [42). Passive cell death via necrosis, on the other hand, is accompanied with swelling of cytoplasm and cell organelles followed by loss of membrane integrity and inflammation [43).…”

Section: Ccf-sttglmentioning

confidence: 99%

Toxicity of organic and inorganic mercury species in differentiated human neurons and human astrocytes

Lohren

Blagojevic

Fitkau

et al. 2015

Journal of Trace Elements in Medicine and Biology

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“…21 It is possible that this form of death may overlap with other types of death being unraveled and in the future it may be possible to determine whether this pathway involves ER stress and/or mitochondrial events.…”

Section: Excitotoxicitymentioning

confidence: 99%

Classification of cell death: recommendations of the Nomenclature Committee on Cell Death

et al. 2005

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“…Retinal degeneration due to unregulated Ca 2+ levels Precise control over Ca 2+ levels is essential for photoreceptor cell survival [226]. Either high or low levels of Ca 2+ are toxic to the cells.…”

Section: Retinal Degenerationmentioning

confidence: 99%

Phototransduction and retinal degeneration in Drosophila

Wang

Montell

2007

Pflugers Arch - Eur J Physiol

256

301

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Drosophila visual transduction is the fastest known G-protein-coupled signaling cascade and has therefore served as a genetically tractable animal model for characterizing rapid responses to sensory stimulation. Mutations in over 30 genes have been identified, which affect activation, adaptation, or termination of the photoresponse. Based on analyses of these genes, a model for phototransduction has emerged, which involves phosphoinoside signaling and culminates with opening of the TRP and TRPL cation channels. Many of the proteins that function in phototransduction are coupled to the PDZ containing scaffold protein INAD and form a supramolecular signaling complex, the signalplex. Arrestin, TRPL, and Gα q undergo dynamic light-dependent trafficking, and these movements function in long-term adaptation. Other proteins play important roles either in the formation or maturation of rhodopsin, or in regeneration of phosphatidylinositol 4,5-bisphosphate (PIP 2 ), which is required for the photoresponse. Mutation of nearly any gene that functions in the photoresponse results in retinal degeneration. The underlying bases of photoreceptor cell death are diverse and involve mechanisms such as excessive endocytosis of rhodopsin due to stable rhodopsin/arrestin complexes and abnormally low or high levels of Ca 2+ . Drosophila visual transduction appears to have particular relevance to the cascade in the intrinsically photosensitive retinal ganglion cells in mammals, as the photoresponse in these latter cells appears to operate through a remarkably similar mechanism.

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Regulation of cell death: the calcium–apoptosis link

Cited by 2,633 publications

References 135 publications

Toxicity of organic and inorganic mercury species in differentiated human neurons and human astrocytes

Toxicity of organic and inorganic mercury species in differentiated human neurons and human astrocytes

Classification of cell death: recommendations of the Nomenclature Committee on Cell Death

Phototransduction and retinal degeneration in Drosophila

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