Reversible phosphorylation of tau to form A68 in heat-shocked neuronal PC12 cells

Wallace, William; Johnson, G.; Sugar, Joel; Merril, Carl R.; Refolo, Lorenzo M.

doi:10.1016/0169-328x(93)90160-q

Cited by 15 publications

(17 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand increased phosphorylation of tau has been reported in neurons or neuroblastoma cells in culture after treatment with glutamate [38], NMDA [44], or insulin [45] among others in the absence of temperature change. Heat shock to 45°C actually produced reversible phosphorylation of tau in PC12 cells [46]. Considering also that we observed qualitatively similar patterns of tau phosphorylation and concurrent TPKI/GSK3b-Ser9 phosphorylation with our three very different stress stimuli, it seems more plausible to view in vivo tau phosphorylation we observed as a molecular event associated with the activation of stress response neural system.…”

Section: Discussionsupporting

confidence: 81%

Ether stress‐induced Alzheimer‐like tau phosphorylation in the normal mouse brain

2007

View full text Add to dashboard Cite

Tau is reversibly hyperphosphorylated in the mouse brain by starvation or cold water swimming. Here, we report tau phosphorylation in the hippocampus of normal mouse after ether anesthesia, known to trigger typical stress reactions. Robust phosphorylation of tau was observed immediately and 10 min after ether vapor exposure at Ser202/Thr205 and Thr231/Ser235, sites typically phosphorylated in Alzheimer brains. The phosphorylation levels returned to baseline by 1 h. The most conspicuous and consistent change in the protein kinases studied was the inactivating phosphorylation of Ser9 of TPKI/GSK3b in close correspondence with tau phosphorylation. These findings show that tau phosphorylation is a rapid physiological process integral to stress response system, and suggest involvement therein of TPKI/GSK3b.

show abstract

Section: Discussionsupporting

confidence: 81%

Ether stress‐induced Alzheimer‐like tau phosphorylation in the normal mouse brain

2007

View full text Add to dashboard Cite

show abstract

“…It has been shown that, in PC12 cells, heat shock induces the formation of a phosphorylated tau protein with immunochemical, biochemical, and electrophoretic characteristics identical to those of A68 proteins isolated from the brains of patients with AD (Wallace et al, 1993). The results reported here indicate that this protein is localized to a triangular region of the perinuclear cytoplasm and has immunocytochemical properties and electrophoretic mobility (Fig.…”

Section: Discussionsupporting

confidence: 67%

“…We have employed a rat pheochromocytoma cell line (PC12) that is differentiated in the presence of nerve growth factor (␤NGF) into neuron-like cells. With heat shock, these cells lose their neurite-like processes, assume a more rounded shape, and produce a PHF-tau-like protein that immunoprecipitates with Alz-50 and has electrophoretic mobilities identical to those of hyperphosphorylated tau proteins, termed A68 proteins (Wallace et al, 1993). If they are allowed to recover following heat shock, a decrease in A68-like proteins occurs accompanied by an increase in normal tau, indicating the reversibility of the heat-shock reaction (Wallace et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Production of paired helical filament, tau-like proteins by PC12 cells: A model of neurofibrillary degeneration

1998

View full text Add to dashboard Cite

Neuron-like cells derived from a rat pheochromocytoma cell line (PC12) and differentiated with nerve growth factor produce a paired helical filament (PHF)-like antigen when they are subjected to heat shock (Wallace et al.: Mol Brain Res 19:149-155, 1993). It accumulates in a localized region of the perinuclear cytoplasm and reacts with monoclonal antitau antibodies, which identify epitopes in the N- and C-terminal halves and the microtubule-binding domain of tau protein. The observed profile of immunoreactivity suggests the presence of full-length and C-terminally truncated tau in a region of perinuclear cytoplasm in which no structurally intact PHFs could be demonstrated by conventional transmission electron microscopy. The accumulated tau protein colocalized with antibodies raised against mitochondrial outer membrane proteins and was associated with the presence of numerous mitochondrial profiles that were demonstrated with electron microscopy. Because differentiated PC12 cells pretreated with colcemid or Taxol prior to heat shock fail to exhibit perinuclear PHF-like immunoreactivity, the reported response to heat shock appears to require an intact system of intracellular microtubules. This PC12 system provides a model in which the metabolic and molecular biological underpinnings of neuronal degeneration in Alzheimer's disease can be manipulated. The system may eventually be applicable to the development of pharmaceutical agents that interfere with formation and/or degeneration of PHF-tau in Alzheimer's disease.

show abstract

“…Although the present study does not address directly the possibility that agonal fever might also alter the amount or the physiological state of a number of other brain constituents that have been associated with AD neuropathology, it suggests that altered levels of ubiquitin mRNAs (Nowak et al, 1990), amyloid precursor protein mRNAs (Abe et al ., 1991 ), or c-.ft) .r mRNAs (Colotta et al, 1990) in AD brain may sometimes result, at least in part, from a physiological response to agonal fever . Similarly, agonal fever has the potential to increase levels of phosphorylated T (Papasozomenos and Su, 1991 ;Wallace et al, 1993) and glial fibrillary acidic proteins, as well as to alter the physiological state of amyloid precursor protein ) . An analysis of patterns of expression of these brain constituents in AD and control patients, individually evaluated for the absence of fever in the last week of life, will be necessary to determine whether measured changes are a consequence solely of the disease or whether agonal stress is at times a contributing factor .…”

Section: Discussionmentioning

confidence: 99%

Heat‐Shock 70 Messenger RNA Levels in Human Brain: Correlation with Agonal Fever

Morrison‐Bogorad

Zimmerman²,

Pardue³

1995

Journal of Neurochemistry

View full text Add to dashboard Cite

Systematic review of antemortem clinical information on randomly selected Alzheimer disease (AD) patients revealed that -40% of the patients had a recorded fever of X39 .2°C at or near death . Using isolation and quantitation techniques appropriate for analysis of human brain mRNAs, we found that low levels of inducible heatshock protein 70 (hsp70) mRNAs were present in cerebellum of afebrile AD patients and that mRNA levels were usually lower in two brain regions affected in AD, i .e ., hippocampus and temporal cortex . Levels of hsp70 mRNAs were increased three-to 33-fold in cerebellum of febrile patients compared with levels in patients whose recorded temperatures were -37 .5°C . Levels of hsp70 mRNAs were also increased in hippocampus and cortex of these febrile patients, but to a lesser extent than cerebellum . Heat-shock cognate 70 (hsc70) mRNAs were present at highest levels in afebrile cerebellum and were also present in the other brain regions . In cerebellum of patients with the highest temperatures, hsc70 mRNAs were induced severalfold over basal levels . Although there was a low and variable induction of hsc70 mRNAs in temporal cortex of these patients, there was no evidence for any induction in hippocampus . Increased heatshock 70 mRNA levels did not correlate with hypoxia, coma, hypertension, hypoglycemia, seizures, or medication . These results indicate that a specific agonal stress, namely fever, can increase the levels of heat shock 70 mRNAs in AD brain ; however, there is no evidence to suggest that affected regions of AD brain have higher overall levels of these mRNAs . Failure to obtain adequate agonal state information could result in inaccurately identifying short-term stress-related changes in postmortem brain as neuropathology characteristic of a chronic disease state . Key Words : Alzheimer disease-Agonal stress-Heat-shock response-hsp70 mRNA induction .

show abstract

Reversible phosphorylation of tau to form A68 in heat-shocked neuronal PC12 cells

Cited by 15 publications

References 19 publications

Ether stress‐induced Alzheimer‐like tau phosphorylation in the normal mouse brain

Ether stress‐induced Alzheimer‐like tau phosphorylation in the normal mouse brain

Production of paired helical filament, tau-like proteins by PC12 cells: A model of neurofibrillary degeneration

Heat‐Shock 70 Messenger RNA Levels in Human Brain: Correlation with Agonal Fever

Contact Info

Product

Resources

About