Induction of Alzheimer-specific tau epitope AT100 in apoptotic human fetal astrocytes

Księżak-Reding, Hanna; He, Deke; Gordon‐Krajcer, Wanda; Kress, Yvonne; Lee, Sunhee; Dickson, Dennis W.

doi:10.1002/1097-0169(200011)47:3<236::aid-cm6>3.0.co;2-k

Cited by 20 publications

(6 citation statements)

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“…These data are consistent with fact that Tau is hyperphosphorylated in cell models using the PP2A inhibitor, okadaic acid (Mailliot et al . 1998; Ksiezak‐Reding et al . 2000).…”

Section: Discussionmentioning

confidence: 99%

“…For instance, the Alzheimer‐like modification of Tau in Xenopus oocyte does not require any drug or inhibitor unlike transfected cell lines that should be treated with the phosphatases inhibitor okadaic acid (Mailliot et al . 1998; Ksiezak‐Reding et al . 2000), nocodazole or taxotere (Illenberger et al .…”

Section: Discussionmentioning

confidence: 99%

“…Only okadaic acid treatment, which inhibits PP2A and PP1, allows for the genesis of these Alzheimer‐type epitopes in cell culture (Mailliot et al . 1998; Ksiezak‐Reding et al . 2000).…”

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confidence: 99%

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Abnormal Tau phosphorylation of the Alzheimer‐type also occurs during mitosis

Delobel

Flament

Hamdane

et al. 2002

Journal of Neurochemistry

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In Alzheimer's disease, neurofibrillary degeneration results from the aggregation of abnormally phosphorylated Tau proteins into filaments and it may be related to the reactivation of mitotic mechanisms. In order to investigate the link between Tau phosphorylation and mitosis, Xenopus laevis oocytes in which most of the M-phase regulators have been discovered were used as a cell model. The human Tau isoform htau412 (2+3-10+) was microinjected into prophase I oocytes that were then stimulated by progesterone that activate cyclindependent kinase pathways. Hyperphosphorylation of the Tau isoform, which is characterized by a decrease of its electrophoretic mobility and its labelling by a number of phosphorylation-dependent antibodies, was observed at the time of germinal vesicle breakdown. Surprisingly, Tau immunoreactivity, considered as typical of Alzheimer's pathology (AT100 and phospho-Ser422), was observed in meiosis II. Because meiosis II is considered as a mitosis-like phase, we investigated if our observation was also relevant to a neuronelike model. Abnormal Tau phosphorylation was detected in mitotic human neuroblastoma SY5Y cells overexpressing Tau. Regarding AT100-immunoreactivity and phosphoSer422, we suggest that phosphatase 2A inhibition and a phosphorylation combination of mitotic kinases may lead to this Alzheimer-type phosphorylation. Our results not only demonstrate the involvement of mitotic kinases in Alzheimertype Tau phosphorylation but also indicate that Xenopus oocyte could be a useful model to identify the kinases involved in this process. Keywords: Alzheimer's disease, microtubule-associated Tau proteins, mitosis, oocyte maturation, phosphorylation. The mechanisms leading to neurodegenerative disorders referred to as tauopathies, such as Alzheimer's disease (AD) are still unknown but recent evidences had shown that neurones affected in these diseases and undergoing neurofibrillary degeneration may re-express some cell cycle genes notably implicated in the G 2 /M transition (Vincent et al. 1998;Husseman et al. 2000).Neurofibrillary degeneration is one of the neuropathological hallmarks of AD. It results from the aggregation of abnormally phosphorylated Tau proteins into paired helical filaments (PHFs). Tau proteins are mainly found in neurones. They play important roles in the polymerization and stability of microtubules (MTs). Moreover, phosphorylation is a key post-translational modification involved in their regulation. At least 30 phosphorylation sites have been described in Tau proteins, most of which occur on Ser/Pro and Thr/Pro motifs.Despite the fact that many phosphorylation sites are common between Tau aggregated into filaments in AD and normal Tau from biopsy-derived material, some differences exist and support the idea of an abnormal phosphorylation of Tau proteins in AD (for review see Buée et al. 2000). This latter is also a common feature among tauopathies. Despite the lack of evidence, a possible link may exist between abnormal Tau

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“…These data are consistent with fact that Tau is hyperphosphorylated in cell models using the PP2A inhibitor, okadaic acid (Mailliot et al . 1998; Ksiezak‐Reding et al . 2000).…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Abnormal Tau phosphorylation of the Alzheimer‐type also occurs during mitosis

Delobel

Flament

Hamdane

et al. 2002

Journal of Neurochemistry

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“…These findings are in agreement with previous studies in apoptotic PC12 cells (Nuydens et al, 1997; Davis and Johnson, 1999a,b). In addition, a recent study presented evidence that tau is hyperphosphorylated at the AT100 epitope in apoptotic human fetal astrocytes (Ksiezak‐Reding et al, 2000) indicating that increased tau phosphorylation may be a generalized outcome of apoptotic cascades. Increased tau phosphorylation should result in a decreased association with microtubules.…”

Section: Discussionmentioning

confidence: 99%

“…In these cells, however, there was almost no total tau immunoreactivity, indicating that tau, as well as other proteins, was dephosphorylated and degraded at the end of the apoptotic process. Therefore, tau is hyperphosphorylated during the early stages of the apoptotic process when cytoskeletal rearrangements are occurring (Nuydens et al, 1997; Davis and Johnson, 1999a; Patrick et al, 1999; Ksiezak‐Reding et al, 2000), but in the end stages of apoptosis when the cell is in the final stages of disposing of itself, tau along with most proteins, is degraded. A dephosphorylated 17 kDa fragment of tau was also seen in the later stages of apoptosis in serum and potassium deprived cerebellar granule cells (Canu et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Tau and HMW tau phosphorylation and compartmentalization in apoptotic neuronal PC12 cells

Shelton

Johnson

2001

J of Neuroscience Research

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In the Alzheimer disease brain, the microtubule-associated protein tau is hyperphosphorylated. There is also evidence that apoptotic-like processes may contribute to the neuronal loss in AD. In an apoptotic model that involves replating neuronal PC12 cells without serum and nerve growth factor (NGF), tau was hyperphosphorylated. During replating, however, neurites are removed. Here, differentiated cells were maintained in serum-free media before growth factor removal, thus maintaining neuritic processes during the apoptotic process and allowing for evaluation of neuritic changes. Tau phosphorylation, evaluated by immunoblotting and immunocytochemistry, was compared with various measures of cell death. Compared with control, NGF-deprived cells exhibited gradual and consistent increases of lactate dehydrogenase release over a 5-day period and a peak of caspase-3 activity at Day 2 after NGF removal. Nuclear staining demonstrated chromatin condensation in NGF-deprived cells. Apoptotic cells had thickened, tortuous, and shortened neuritic processes compared with control cells. Immunoblotting showed an increase in both tau and high molecular weight (HMW) tau phosphorylation during the apoptotic process. Immunoreactivity of both tau isoforms shifted from the detergent insoluble cytoskeleton to the detergent soluble compartment in the apoptotic cells. The microtubule binding of both tau isoforms from apoptotic cells also was impaired. Immunoblotting of purified plasma membrane showed preferential association of HMW tau with the plasma membrane during apoptosis. Also, plasma membrane-associated HMW tau was more phosphorylated during apoptosis. Immunocytochemistry demonstrated increased tau phosphorylation in most apoptotic cells, especially in the neurites. Tau was, however, dephosphorylated cells in the last stages of apoptosis.

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Ischemia‐induced programmed cell death in astrocytes

Giffard

Swanson

2005

Glia

150

120

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Astrocytes are essential for neuronal survival and function, neurogenesis, and neural repair. Although astrocytes are more resistant than neurons to most stress conditions in vitro, certain astrocyte subtypes, such as the glial fibrillary acidic protein (GFAP)-negative protoplasmic astrocytes that predominate in gray matter structures, may be equally or more sensitive than neurons to ischemia in vivo. Programmed cell death differs from passive, necrotic death in that cell constituents actively participate in cell demise. Like neurons, astrocytes undergo programmed cell death during normal development. Cell culture studies have shown that astrocytes can be induced to undergo apoptosis and other forms of programmed cell death by many factors relevant to ischemia, including acidosis, oxidative stress, substrate deprivation, and cytokines. Animal models of cerebral ischemia have confirmed nuclear condensation and upregulation of Bax and caspases in a subset of astrocytes exposed to ischemia, especially in immature brain. A causal role for these events in astrocyte death is supported by improved astrocyte survival after inhibition of caspase-dependent cell death pathways. Astrocyte survival is also improved by blocking the poly(ADP-ribose)-1 cell death pathway. Markers of programmed cell death are generally less evident and less widespread in astrocytes than in neighboring neurons. However, most studies to date have relied only on markers of classical apoptosis. In addition, these studies have relied almost exclusively on GFAP to identify astrocytes. Since most protoplasmic astrocytes are poorly immunoreactive for GFAP, the extent of ischemia-induced programmed cell death in this cell type remains uncertain.

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Induction of Alzheimer-specific tau epitope AT100 in apoptotic human fetal astrocytes

Cited by 20 publications

References 85 publications

Abnormal Tau phosphorylation of the Alzheimer‐type also occurs during mitosis

Abnormal Tau phosphorylation of the Alzheimer‐type also occurs during mitosis

Tau and HMW tau phosphorylation and compartmentalization in apoptotic neuronal PC12 cells

Ischemia‐induced programmed cell death in astrocytes

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