Proteomic study of neuron and astrocyte cultures from senescence‐accelerated mouse SAMP8 reveals degenerative changes

Díez‐Vives, Cristina; García-Matas, Silvia; Comellas, Francesc; Carrascal, Montserrat; Abian, Joaquín; Ortega‐Aznar, Arantxa; Cristòfol, Rosa; Sanfeliu, Coral

doi:10.1111/j.1471-4159.2009.06374.x

Cited by 23 publications

(16 citation statements)

References 48 publications

(90 reference statements)

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“…We describe that nonneoplastic astrocytes had virtually a complete loss of MTAP expression as opposed to the adjacent neoplastic astrocytes. In experimental studies on dementia, MTAP overexpression has been related to senescence and loss of neuroprotective function compared to normal astrocytes [47,48] . We therefore hypothesized that the adjacent cells play an essential role in the establishment of boundaries to the growth of PAs by avoiding these cells from senescence, thereby maintaining their neuroprotective role.…”

Section: Discussionmentioning

confidence: 99%

Expression of Methylthioadenosine Phosphorylase (MTAP) in Pilocytic Astrocytomas

et al. 2015

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Background/Objectives: Pilocytic astrocytomas (PAs) are the most frequent astrocytomas in children and adolescents. Methilthioadenosine phosphorylase(MTAP) is a tumor-suppressor gene, the loss of expression of which is associated with a poor prognosis and better response to specific chemotherapy in leukemia and non-small-cell lung cancer. The expression of MTAP in brain tumors remains largely unknown and its biological role in PA is still unexplored. Our aims were to describe the immunohistochemical MTAP expression in a series of PAs and relate it to the clinicopathological features of the patients. Methods: We assessed MTAP expression on immunohistochemistry in 69 pediatric and adult patients with PA in a tissue microarray platform. Results: Retained expression of MTAP was seen in >85% of the tumors compared to in the nonneoplastic adjacent tissue. Only 3 supratentorial tumors showed a complete loss of MTAP expression. No significant association with clinicopathological features or overall survival of the patients was found. Conclusions: MTAP expression is retained in PAs and is not an outcome predictor for these tumors. Nevertheless, a subset of patients with PAs exhibiting a loss of MTAP could potentially benefit from treatment with specific chemotherapy, especially when lesions are recurrent or surgical resection is not recommended.

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Section: Discussionmentioning

confidence: 99%

Expression of Methylthioadenosine Phosphorylase (MTAP) in Pilocytic Astrocytomas

et al. 2015

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“…It is known that the reduction of the brain volume may be indicative of the development of neurodegenerative disease. [69][70][71] The body weight of OXYS rats at 12 mo of age reaches its maximum and does not yet begin typical age-related decline. Consequently, the decrease of brain volume of OXYS rats by age 12 mo probably points to progressive neurodegenerative changes.…”

Section: Signs Of Neurodegeneration In Oxys Ratsmentioning

confidence: 99%

Senescence-accelerated OXYS rats: A model of age-related cognitive decline with relevance to abnormalities in Alzheimer disease

et al. 2014

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Senescence-accelerated OXYS rats are an experimental model of accelerated aging that was established from wistar stock via selection for susceptibility to cataractogenic effects of a galactose-rich diet and via subsequent inbreeding of highly susceptible rats. Currently, we have the 102nd generation of OXYS rats with spontaneously developing cataract and accelerated senescence syndrome, which means early development of a phenotype similar to human geriatric disorders, including accelerated brain aging. in recent years, our group found strong evidence that OXYS rats are a promising model for studies of the mechanisms of brain aging and neurodegenerative processes similar to those seen in Alzheimer disease (AD). The manifestation of behavioral alterations and learning and memory deficits develop since the fourth week of age, i.e., simultaneously with first signs of neurodegeneration detectable on magnetic resonance imaging and under a light microscope. in addition, impaired long-term potentiation has been demonstrated in OXYS rats by the age of 3 months. with age, neurodegenerative changes in the brain of OXYS rats become amplified. we have shown that this deterioration happens against the background of overproduction of amyloid precursor protein (AβPP), accumulation of β-amyloid (Aβ), and hyperphosphorylation of the tau protein in the hippocampus and cortex. The development of AMDlike retinopathy in OXYS rats is also accompanied by increased accumulation of Aβ in the retina. These published data suggest that the OXYS strain may serve as a spontaneous rat model of AD-like pathology and could help to decipher the pathogenesis of AD.

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“…Thus, enolase could become the immediate targets of free radicals produced by defective mitochondria. Recently, α-enolase was reported to be more oxidatively damaged in AD and in the brain tissues of old mice, which suggest that the enolase activity may be reduced in the affected tissues [63] and that the decrease of α-enolase activity could result in abnormal cell growth and reduced metabolism in the pathogenesis of AD [64]. Therefore, the increase of oxidatively modified α-enolase observed in the MERRF cybrids may imply the alteration of glucose metabolism in the pathology of the MERRF syndrome.…”

Section: Oxidative Damage To Mitochondrial Proteins In the Merrf Skinmentioning

confidence: 99%

Mitochondrial DNA Mutation-Elicited Oxidative Stress, Oxidative Damage, and Altered Gene Expression in Cultured Cells of Patients with MERRF Syndrome

Wu¹,

Ma²,

Wu³

et al. 2010

Mol Neurobiol

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Myoclonic epilepsy and ragged-red fibers (MERRF) syndrome is a rare disorder characterized by myoclonus, muscle weakness, cerebellar ataxia, heart conduction block, and dementia. It has been documented that 80-90% of the patients with MERRF syndrome are caused by the A8344G mutation in the tRNA(Lys) gene of mitochondrial DNA (mtDNA). We and other investigators have reported that the mtDNA mutation results in not only inefficient generation of adenosine triphosphate but also increased production of reactive oxygen species (ROS) in cultured cells harboring A8344G mutation of mtDNA. In addition, we found an imbalance in the gene expression of antioxidant enzymes in the skin fibroblasts of MERRF patients. The mRNA, protein, and enzyme activity levels of manganese-superoxide dismutase were increased, but those of Cu,Zn-SOD, catalase, and glutathione peroxidase did not show significant changes. Recently, we showed that the excess ROS could damage voltage-dependent anion channel, prohibitin, Lon protease, and aconitase in the MERRF cells. Moreover, there was a dramatic increase in the gene expression and activity of matrix metalloproteinase 1, which may contribute to the cytoskeleton remodeling involved in the weakness and atrophy of muscle commonly seen in MERRF patients. Taken together, we suggest that mtDNA mutation-elicited oxidative stress, oxidative damage, and altered gene expression are involved in the pathogenesis and progression of MERRF syndrome.

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Proteomic study of neuron and astrocyte cultures from senescence‐accelerated mouse SAMP8 reveals degenerative changes

Cited by 23 publications

References 48 publications

Expression of Methylthioadenosine Phosphorylase (MTAP) in Pilocytic Astrocytomas

Expression of Methylthioadenosine Phosphorylase (MTAP) in Pilocytic Astrocytomas

Senescence-accelerated OXYS rats: A model of age-related cognitive decline with relevance to abnormalities in Alzheimer disease

Mitochondrial DNA Mutation-Elicited Oxidative Stress, Oxidative Damage, and Altered Gene Expression in Cultured Cells of Patients with MERRF Syndrome

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