Apoptosis and expression of DNA repair proteins in ischaemic brain injury in man

Love, Seth; Barber, Rachel; Wilcock, Gordon

doi:10.1097/00001756-199804200-00001

Cited by 60 publications

(38 citation statements)

References 7 publications

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“…We compared a number of methods with TUNEL, including Ku80 44 immunohistochemical analysis (data not shown). Similar results were observed with the comparative methods, but we found that TUNEL afforded increased specific colorstaining identification, enabling easy interpretation and quantitation.…”

Section: Discussionmentioning

confidence: 99%

Correlation between neurological progression and astrocyte apoptosis in HIV-associated dementia

2001

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The pathogenesis of HIV-associated dementia (HIVD) has been postulated to be due to the indirect effects of HIV infection, including the aberrant central nervous system production of cytokines and other neurotoxins. A correlation between the severity of dementia and production of neurotoxins in HIVD has been demonstrated. We have previously identified nonproductive HIV infection of astrocytes. Because astrocytes participate in the inactivation of neurotoxins, we hypothesize that HIV nonproductive infection of astrocytes may lead to an environment in which there is a significant level of astrocyte apoptosis and a consequent increase in the levels of neurotoxins and that this results in more rapidly progressing dementia. Postmortem brain tissue was examined from clinically well-characterized HIV-positive demented patients, HIV-positive nondemented patients, and HIV-seronegative nondemented control subjects. The HIVD group was further categorized into subjects with rapid and those with slow progression of dementia. Tissue was paraformaldehyde fixed and paraffin embedded, and 6-microm sections from the basal ganglia and mid-frontal gyrus were processed to detect apoptosis by in situ transferase dUTP nick end labeling. Astrocytes were co-localized using immunohistochemical techniques. In situ polymerase chain reaction (PCR) techniques were utilized to detect HIV DNA in astrocytes. The density of apoptotic astrocytes was significantly greater in the HIV-positive groups than in the HIV-negative group (p < 0.01). The HIVD rapid progressors had a significantly greater number of apoptotic astrocytes in the basal ganglia than did the HIVD slow progressors (p < 0.05). In addition, there were a greater number of HIV DNA-positive astrocytes, as demonstrated by in situ PCR, in the HIVD rapid progressors than in the slow progressor and HIV-nondemented groups. These data suggest that there is an increased rate of astrocyte loss in the subjects with rapidly progressive dementia, in association with an increased number of HIV DNA-positive astrocytes. The results emphasize the importance of understanding more completely the role of HIV infection of astrocytes in the neuropathogenesis of HIVD.

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Section: Discussionmentioning

confidence: 99%

Correlation between neurological progression and astrocyte apoptosis in HIV-associated dementia

2001

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“…Although a variety of initiating factors may contribute to such cell deaths, they appear to involve a shared biochemical cascade involving oxidative stress, overactivation of glutamate receptors, activation of caspases, and mitochondrial dysfunction. DNA damage has been documented in Alzheimer's disease and stroke patients (Love et al, 1998;Torp et al, 1998;Adamec et al, 1999) and in experimental models of these disorders (Bozner et al, 1997;Hou et al, 1997). DNA damage in neurons may trigger a cell death cascade involving activation of poly-ADP-ribose polymerase (PARP) (for review, see Pieper et al, 1999) and induction of the tumor suppressor protein p53 (for review, see Hughes et al, 1997).…”

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confidence: 99%

Homocysteine Elicits a DNA Damage Response in Neurons That Promotes Apoptosis and Hypersensitivity to Excitotoxicity

et al. 2000

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Elevated plasma levels of the sulfur-containing amino acid homocysteine increase the risk for atherosclerosis, stroke, and possibly Alzheimer's disease, but the underlying mechanisms are unknown. We now report that homocysteine induces apoptosis in rat hippocampal neurons. DNA strand breaks and associated activation of poly-ADP-ribose polymerase (PARP) and NAD depletion occur rapidly after exposure to homocysteine and precede mitochondrial dysfunction, oxidative stress, and caspase activation. The PARP inhibitor 3-aminobenzamide (3AB) protects neurons against homocysteine-induced NAD depletion, loss of mitochondrial transmembrane potential, and cell death, demonstrating a requirement for PARP activation and/or NAD depletion in homocysteine-induced apoptosis. Caspase inhibition accelerates the loss of mitochondrial potential and shifts the mode of cell death to necrosis; inhibition of PARP with 3AB attenuates this effect of caspase inhibition. Homocysteine markedly increases the vulnerability of hippocampal neurons to excitotoxic and oxidative injury in cell culture and in vivo, suggesting a mechanism by which homocysteine may contribute to the pathogenesis of neurodegenerative disorders.

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“…Оценка уровня однонитевых разрывов ДНК в нейронах различных областей мозга крыс линии Wistar и линий с различным уровнем возбудимости нервной систе-мы после короткого и длительного эмоционально-бо-левого стрессирования показала, что острый стресс вызывает изменения в нейронах среднего мозга крыс линии Wistar, тогда как длительный -в нейронах сред-него мозга и гиппокампа низковозбудимых крыс линии ВП [160]. Ишемия мозга, глюкозная нагрузка, помеще-ние животных в новые условия, стрессорные воздейст-вия (вынужденное плавание и иммобилизация) вызы-вают двунитевые разрывы ДНК в нейронах [161][162][163], что может приводить к апоптотической гибели клеток. Вместе с тем возникновение двунитевых разрывов ДНК рассматривается в последнее время как отражение нор-мальных явлений пластичности генома нейронов, лежа-щих в основе их активности и связанных с обеспече-нием динамических взаимодействий генома с влиянием среды, необходимых для формирования адаптивных ре-акций, процессов обучения и памяти [164][165][166].…”

Section: структурные изменения в днкunclassified

Genome and stress-reaction in animals and humans

Dyuzhikova

Алековна²,

Даев

et al. 2018

Ecological genetics

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Current data on the effects of stress at the level of the cell genomes of the central nervous system and peripheral organs in animals are discussed. Regulatory and structural genomic changes in the cells of the central nervous system under stress are considered as a mechanism for regulating the functions of the brain and peripheral organs that form the organism manifestations of stress. Based on the Yu.Ya. Kerkis and M.E. Lobashev point of view, we consider stress as a special physiological state of the nervous system, affecting the work and integrity of the genome in target cells in animals, and thus playing a major role in microevolutionary transformations.

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Apoptosis and expression of DNA repair proteins in ischaemic brain injury in man

Cited by 60 publications

References 7 publications

Correlation between neurological progression and astrocyte apoptosis in HIV-associated dementia

Correlation between neurological progression and astrocyte apoptosis in HIV-associated dementia

Homocysteine Elicits a DNA Damage Response in Neurons That Promotes Apoptosis and Hypersensitivity to Excitotoxicity

Genome and stress-reaction in animals and humans

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