Cultured neurons expressing phosphorylated tau are more resistant to apoptosis induced by NMDA or serum deprivation

Lesort, Mathieu; Blanchard, Cécile; Yardin, Catherine; Esclaire, Françoise; Hugon, Jacques

doi:10.1016/s0169-328x(96)00284-7

Cited by 41 publications

(30 citation statements)

References 27 publications

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“…However, its role in AD pathogenesis, especially in cell loss, is still not understood. The results observed in this study are consistent with the observations of SY5Y cells that tau phosphorylation can be an anti-apoptosis [25] . In another project, we also found that treatment of cells with calyculin A (a protein phosphatase inhibitor) led to neurofilament hyperphosphorylation and aggregation with minimal apoptosis [12] .…”

Section: Discussionsupporting

confidence: 93%

Effects of melatonin on wortmannin-induced tau hyperphosphorylation

yan-qiu

Duan

et al. 2005

Acta Pharmacol Sin

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Aim: To explore the underlying mechanism of tau hyperphosphorylation in an Alzheimer's-affected brain and the possible arresting strategies. Methods: MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide), crystal violet assay, phase-contrast, dead end colorimetric apoptosis detection system (TUNEL) and electron microscopy were used to detect cell viability, morphology and apoptosis. Western blot, 32 P-labeling and the detection of malondialdehyde level and superoxide dismutase activity were used respectively for the phosphorylation level of tau, the activity of glycogen synthase kinase (GSK-3), and oxidative stress measurement. Results: Exposure of the cells to wortmannin resulted in an obvious lipid peroxidation, reduction of cell viability, cell process retraction, and plasma vacuolation, but with no obvious cell apoptosis. We also found that preincubation of the cells with melatonin or vitamin E attenuated differentially wortmannininduced oxidative stress as well as GSK-3 overactivation and tau hyperphosphorylation. Conclusion: Wortmannin is an effective tool for reproducing Alzheimer-like tau hyperphosphorylation cell model and melatonin/vitamin E can effectively protect the cells from wortmannin-induced impairments.

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Section: Discussionsupporting

confidence: 93%

Effects of melatonin on wortmannin-induced tau hyperphosphorylation

yan-qiu

Duan

et al. 2005

Acta Pharmacol Sin

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“…Many researchers have used the in vitro paradigm of serum deprivation to induce PCD in either neuronal cell lines such as PC12 (Lindenboim et al, 1995) and primary cultures of neurons (Lesort et al, 1997;Troy et al, 1997). In the present study, we have found that the SJ3.6 cell line appeared to activate PCD without requiring the withdrawal of serum factors.…”

Section: Cn14 Cell Line Survives At the Nonpermissive Temperature Bsupporting

confidence: 58%

Two neuronal cell lines expressing the myelin basic protein gene display differences in their in vitro survival and in their response to glia

et al. 1998

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We have generated two conditionally immortalized neuronal cell lines from primary cultures of embryonic day 13 (E13) and postmitotic (postnatal day 0; P0) cortical neurons transformed with the temperature-sensitive SV-40 large-T antigen. Two clonal cell lines (CN1.4 from E13 cultures and SJ3.6 from P0 cultures) were isolated and stable maintained in vitro. Both cell lines expressed a number of neuronal markers such as the neurofilaments, glutamic acid decarboxylase 67, neuron-specific enolase, and the BG21 isoform of the myelin basic protein gene. At 34 degrees C, the CN1.4 cell line had elaborated short processes, whereas the SJ3.6 cell line produced long processes that formed a delicate network. When these cell lines were cultured at 39 degrees C, some of the cellular processes grew longer, adopting a more mature neuronal morphology. Interestingly, at 39 degrees C, the in vitro survival of these cell lines differed significantly. Whereas the survival of CN1.4 cell line was greatly unaffected, SJ3.6 cells died soon after they were cultured at 39 degrees C. The cell death of SJ3.6 cells was accompanied by fragmentation and condensation of DNA in their nuclei, indicative of an apoptotic event. Under these conditions, SJ3.6 showed an upregulation of the p75 receptor. When this cell line was cocultured with oligodendrocytes, astrocytes, or glial conditioned media (GCM), there was a marked increase in survival. In contrast, little effect of glial cells or GCM was observed on the CN1.4 cell line. These lines appear to be useful models to study neuronal-glial interactions in addition to neuronal cell death and the effects of glial factors that promote the survival of neurons.

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“…additional functions beyond its well known role in the dynamics of microtubules. We hypothesize that the co-localization of HO-1 and the pathological form of the tau protein may be protective responses against oxidative stress in neuronal cells (41), which may be mediated through ERK cascades. In fact, neurons that express phosphorylated tau are more resistant to cell death (41) supporting this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Heme Oxygenase in Neuronal Cells, the Possible Interaction with Tau

Takeda

Perry

Abraham

et al. 2000

Journal of Biological Chemistry

176

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Increased expression of heme oxygenase-1 (HO-1) is a common feature in a number of neurodegenerative diseases. Interestingly, the spatial distribution of HO-1 expression in diseased brain is essentially identical to that of pathological expression of tau. In this study, we explored the relationship between HO-1 and tau, using neuroblastoma cells stably transfected with sense and antisense HO-1 constructs as well as with the vector alone. In transfected cells overexpressing HO-1, the activity of heme oxygenase was increased, and conversely, the level of tau protein was dramatically decreased when compared with antisense HO-1 or CEP transfected cells. The suppression of tau protein expression was almost completely reversed by zinc-deuteroporphyrin, a specific inhibitor of heme oxygenase activity. The activated forms of ERKs (extracellular signal-regulated kinases) were also decreased in cells overexpressing HO-1 although no changes in the expression of total ERK-1/2 proteins were observed. These data are in agreement with the finding that the expression of tau is regulated through signal cascades including the ERKs, whose activities are modulated by oxidative stresses. The expression of tau and HO-1 may be regulated by oxidative stresses in a coordinated manner and play a pivotal role in the cytoprotection of neuronal cells. Heme oxygenase (HO)1 is a microsomal enzyme that cleaves heme, a pro-oxidant, to produce biliverdin and carbon monoxide (1). Biliverdin is converted to a potent antioxidant (2), bilirubin, and carbon monoxide has been implicated to be a physiological regulator of cGMP and vascular tone (3, 4). The HO system is the rate-limiting step in heme degradation. To date, three HO isoforms (HO-1, HO-2, and HO-3) have been identified that catalyze this reaction. HO-1 is a 32-kDa heat shock protein (1, 5), which is inducible by numerous noxious stimuli (6, 7). HO-2 is a constitutively synthesized 36-kDa protein which is abundant in brain and testis (8). HO-3 is related to HO-2 but is the product of a different gene, and its ability to catalyze heme degradation is much less than that of HO-1 (9). Within the brain, the majority of HO activity is attributed to the HO-2 isozyme (8). The expression of HO-1 is normally very low in the brain but increases markedly after heat shock, ischemia, or glutathione depletion (8, 10 -12). In the normal rat brain, HO-1 is restricted to select neuronal and non-neuronal cell populations in the forebrain, diencephalon, cerebellum, and brainstem (10). However, after heat shock or ischemia, increased HO-1 is seen in neuronal and glial cells throughout the brain (10,(12)(13)(14).While the long-lived lesions of Alzheimer disease (AD) provide ample opportunity for oxidative modification because of their low rate of turnover (15), the more important issue is when, during the course of AD, oxidative abnormalities actually develop. Recent studies show that the oxidative damage associated with AD is represented by lipid peroxidation (16), nitration (17), reactive carbonyls (18), and n...

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Cultured neurons expressing phosphorylated tau are more resistant to apoptosis induced by NMDA or serum deprivation

Cited by 41 publications

References 27 publications

Effects of melatonin on wortmannin-induced tau hyperphosphorylation

Effects of melatonin on wortmannin-induced tau hyperphosphorylation

Two neuronal cell lines expressing the myelin basic protein gene display differences in their in vitro survival and in their response to glia

Overexpression of Heme Oxygenase in Neuronal Cells, the Possible Interaction with Tau

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