Death‐associated protein kinase expression in human temporal lobe epilepsy

Henshall, David C.; Schindler, Clara K.; So, Norman K.; Lan, Jing-Quan; Meller, Robert; Simon, Roger P.

doi:10.1002/ana.20001

Cited by 44 publications

(49 citation statements)

References 59 publications

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“…Considering that the expression of the ubiquitin E3 ligase DIP-1 for DAPK-1 promotes TNF-␣-induced apoptosis (28), there may be a link between the ubiquitination of DAPK-1, its interaction with cathepsin B, and TNF apoptotic responses. DAPK-1 is known to bind to early responsive components in the TNF-␣ pathway, including TNFR-1 and FADD after brain seizures, although the function of these bindings is still unclear (32,33). Whether these binding interactions are linked to the proapoptotic ERK pathway remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Dominant Negative Functional Domain on DAPK-1 That Degrades DAPK-1 Protein and Stimulates TNFR-1-mediated Apoptosis

Lin

Stevens

Hupp

2007

Journal of Biological Chemistry

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DAPK-1 is a stress-activated tumor suppressor protein that plays a role in both proapoptotic or antiapoptotic signal transduction pathways. To define mechanisms of DAPK-1 protein regulation, we have determined that DAPK-1 protein has a long half-life, and therefore its activity is primarily regulated at the protein level. Changes in DAPK-1 protein levels occur by a cathepsin B-dependent pathway, prompting us to evaluate whether cathepsin B plays positive or negative role in DAPK-1 function. The transfection of p55-TNFR-1 induced complex formation between DAPK-1 and cathepsin B. Depletion of cathepsin B protein using small interfering RNA stimulated TNFR-1 dependent apoptosis. The minimal binding region on DAPK-1 for cathepsin B was mapped to amino acids 836 -947. The transfection of the DAPK-1-(836 -947) miniprotein acted in a dominant negative manner inducing endogenous DAPK-1 protein degradation in a TNFR-1-dependent manner. These data suggest that DAPK-1 forms a multiprotein survival complex with cathepsin B countering the rate of TNFR-1-dependent apoptosis and highlights the importance of developing DAPK-1 inhibitors as agents to sensitize cells to stress-induced apoptosis.

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Section: Discussionmentioning

confidence: 99%

Identification of a Dominant Negative Functional Domain on DAPK-1 That Degrades DAPK-1 Protein and Stimulates TNFR-1-mediated Apoptosis

Lin

Stevens

Hupp

2007

Journal of Biological Chemistry

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“…Altered expression of Bcl-2 family proteins, caspases and other apoptosisregulatory proteins is seen in neocortex and hippocampal resection material from TLE patients with intractable seizures (Henshall et al, 2000(Henshall et al, , 2004Henshall and Simon, 2005). Deoxyribose nucleic acid fragmentation is a commonly reported biochemical feature of seizure-induced neuronal death (Henshall and Simon, 2005), but the enzyme(s) responsible are not known.…”

Section: Discussionmentioning

confidence: 99%

“…Because DNA fragmentation is a consistent finding after experimentally evoked seizures, and apoptosis signaling pathways are activated in human TLE (Henshall et al, 2000(Henshall et al, , 2004Henshall and Simon, 2005), we investigated the localization of CAD in human TLE samples and compared findings to those for AIF and endonuclease G.…”

Section: Introductionmentioning

confidence: 99%

Caspase-3 Cleavage and Nuclear Localization of Caspase-Activated DNase in Human Temporal Lobe Epilepsy

Schindler

Pearson

Bonner

et al. 2005

J Cereb Blood Flow Metab

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Programmed cell death (apoptosis) signaling pathways have been implicated in seizure-induced neuronal death and the pathogenesis of human temporal lobe epilepsy (TLE). End-stage DNA fragmentation during cell death may be mediated by nucleases including caspase-activated DNase (CAD), apoptosis-inducing factor (AIF) and endonuclease G. In the present study, we investigated the subcellular localization of these nucleases in resected hippocampus from TLE patients and autopsy controls. Subcellular fractionation determined levels of CAD were significantly higher in the nuclear fraction of TLE samples compared with controls, and semiquantitative immunohistochemistry revealed cleaved caspase-3 positive cells in TLE sections but not controls. While mitochondrial levels of AIF and endonuclease G were higher in TLE samples than controls, nuclear localization of AIF was limited and restricted to cells that were negative for cleaved caspase-3. Nuclear accumulation of endonuclease G was not found in TLE samples. These data support ongoing caspase-dependent apoptosis signaling in human TLE and suggest that interventions targeting such pathways may have potential as adjunctive neuroprotective therapy in epilepsy.

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Section: Discussionmentioning

confidence: 99%

“…Expression levels of DAPK increase in hippocampal neurons by either seizure or ischemia (17,19,28,29). DAPK is induced to associate with various kinds of apoptosis-related molecules in the hippocampus following seizures (17,19,28). Since DAPK is expressed in a neuron-specific manner in normal hippocampus (15)(16)(17), DAPK may physiologically act as a Ca 2+ -dependent serine/threonine kinase in hippocampal neurons.…”

Section: Discussionmentioning

confidence: 99%

Deletion of the kinase domain from death-associated protein kinase enhances spatial memory in mice

Yukawa

Tanaka²,

Bai³

et al. 2006

Int J Mol Med

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Abstract. Death-associated protein kinase (DAPK) is a Ca 2+ /calmodulin-dependent serine/threonine kinase that is thought to mediate apoptosis. DAPK is highly expressed in hippocampal neurons which are essential elements for memory formation. To examine if DAPK is implicated in spatial learning and memory, both wild-type and DAPK-mutant mice were subjected to Morris water maze tests. DAPKmutant mice were generated by deleting 74 amino acids from the catalytic kinase domain of DAPK, and were used to investigate roles of the DAPK kinase domain in regulating spatial memory. Both mutant and wild-type mice were able to learn the water maze tasks to locate a hidden escape platform. In the first probe test, mutant mice showed a more precise memory for platform position compared to wild-type mice. In the reversal training in which the platform was located opposite from the original position, DAPK-mutant mice exhibited superior spatial learning compared to wildtype mice. DAPK-mutant mice also showed a more precise memory than their wild-type littermates in the probe trial of reversal test. Thus, the present results revealed crucial implications of DAPK in regulating spatial memory in mice.

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Death‐associated protein kinase expression in human temporal lobe epilepsy

Cited by 44 publications

References 59 publications

Identification of a Dominant Negative Functional Domain on DAPK-1 That Degrades DAPK-1 Protein and Stimulates TNFR-1-mediated Apoptosis

Identification of a Dominant Negative Functional Domain on DAPK-1 That Degrades DAPK-1 Protein and Stimulates TNFR-1-mediated Apoptosis

Caspase-3 Cleavage and Nuclear Localization of Caspase-Activated DNase in Human Temporal Lobe Epilepsy

Deletion of the kinase domain from death-associated protein kinase enhances spatial memory in mice

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