scholarly journals Anandamide-induced cell death in primary neuronal cultures: role of calpain and caspase pathways

2004 ◽  
Vol 11 (10) ◽  
pp. 1121-1132 ◽  
Author(s):  
V A Movsesyan ◽  
B A Stoica ◽  
A G Yakovlev ◽  
S M Knoblach ◽  
P M Lea ◽  
...  
2008 ◽  
Vol 62 (6) ◽  
pp. 2325-2332 ◽  
Author(s):  
Yi-Hsuan Lee ◽  
David L. Deupree ◽  
Shine-Chi Chen ◽  
Lung-Sen Kao ◽  
Jang-Yen Wu

2016 ◽  
Vol 37 (6) ◽  
pp. 1982-1993 ◽  
Author(s):  
Jian Zhang ◽  
Xiaoling Li ◽  
Herman Kwansa ◽  
Yun Tai Kim ◽  
Liye Yi ◽  
...  

Tissue acidosis is a key component of cerebral ischemic injury, but its influence on cell death signaling pathways is not well defined. One such pathway is parthanatos, in which oxidative damage to DNA results in activation of poly(ADP-ribose) polymerase and generation of poly(ADP-ribose) polymers that trigger release of mitochondrial apoptosis-inducing factor. In primary neuronal cultures, we first investigated whether acidosis per sé is capable of augmenting parthanatos signaling initiated pharmacologically with the DNA alkylating agent, N-methyl- N′-nitro- N-nitrosoguanidine. Exposure of neurons to medium at pH 6.2 for 4 h after N-methyl- N′-nitro- N-nitrosoguanidine washout increased intracellular calcium and augmented the N-methyl- N′-nitro- N-nitrosoguanidine-evoked increase in poly(ADP-ribose) polymers, nuclear apoptosis-inducing factor , and cell death. The augmented nuclear apoptosis-inducing factor and cell death were blocked by the acid-sensitive ion channel-1a inhibitor, psalmotoxin. In vivo, acute hyperglycemia during transient focal cerebral ischemia augmented tissue acidosis, poly(ADP-ribose) polymers formation, and nuclear apoptosis-inducing factor , which was attenuated by a poly(ADP-ribose) polymerase inhibitor. Infarct volume from hyperglycemic ischemia was decreased in poly(ADP-ribose) polymerase 1-null mice. Collectively, these results demonstrate that acidosis can directly amplify neuronal parthanatos in the absence of ischemia through acid-sensitive ion channel-1a . The results further support parthanatos as one of the mechanisms by which ischemia-associated tissue acidosis augments cell death.


2000 ◽  
Vol 14 (12) ◽  
pp. 1814-1824 ◽  
Author(s):  
Christoph Harms ◽  
Marion Lautenschlager ◽  
Alexandra Bergk ◽  
Dorette Freyer ◽  
Markus Weih ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Anat Idan-Feldman ◽  
Regina Ostritsky ◽  
Illana Gozes

The peptide drug candidate NAP (davunetide) has demonstrated protective effects in variousin vivoandin vitromodels of neurodegeneration. NAP was shown to reduce tau hyperphosphorylation as well as to prevent caspase-3 activation and cytochrome-3 release from mitochondria, both characteristic of apoptotic cell death. Recent studies suggest that caspases may play a role in tau pathology. The purpose of this study was to evaluate the effect of NAP on tau hyperphosphorylation and caspase activity in the same biological system. Our experimental setup used primary neuronal cultures subjected to oxygen-glucose deprivation (OGD), with and without NAP or caspase inhibitor. Cell viability was assessed by measuring mitochondrial activity (MTS assay), and immunoblots were used for analyzing protein level. It was shown that apoptosis was responsible for all cell death occurring following ischemia, and NAP treatment showed a concentration-dependent protection from cell death. Ischemia caused an increase in the levels of active caspase-3 and hyperphosphorylated tau, both of which were prevented by either NAP or caspase-inhibitor treatment. Our data suggest that, in this model system, caspase activation may be an upstream event to tau hyperphosphorylation, although additional studies will be required to fully elucidate the cascade of events.


2000 ◽  
Vol 37 (5-6) ◽  
pp. 497-507 ◽  
Author(s):  
Joseph G. Rudolph ◽  
John J. Lemasters ◽  
Fulton T. Crews

2000 ◽  
Vol 20 (2) ◽  
pp. 396-404 ◽  
Author(s):  
Kohji Matsushita ◽  
Wei Meng ◽  
Xiaoying Wang ◽  
Minoru Asahi ◽  
Kazuko Asahi ◽  
...  

The overall hypothesis that cell death after intracerebral hemorrhage is mediated in part by apoptotic mechanisms was tested. Intracerebral hemorrhage was induced in rats using stereotactic infusions of 0.5 U of collagenase (1-μL volume) into the striatum. After 24 hours, large numbers of TUNEL-positive stained cells with morphologies suggestive of apoptosis were present in the center and periphery of the hemorrhage. Double staining with Nissl and immunocytochemical labeling with antibodies against neuronal nuclei and glial fibrillary acidic protein suggested that these TUNEL-positive cells were mostly neurons and astrocytes. Electrophoresis of hemorrhagic brain extracts showed evidence of DNA laddering into ∼200-bp fragments. Western blots showed cleavage of the cytosolic caspase substrate gelsolin. The density of TUNEL-positive cells at 24 and 48 hours after hemorrhage was significantly reduced by treatment with the broad-spectrum caspase inhibitor zVADfmk. It was unlikely that apoptotic changes were due to neurotoxicity of injected collagenase because TUNEL-positive cells and DNA laddering were also obtained in an alternative model of hemorrhage where autologous blood was infused into the striatum. Furthermore, equivalent doses of collagenase did not induce cell death in primary neuronal cultures. These results provide initial evidence that apoptotic mechanisms may mediate some of the injury in brain after intracerebral hemorrhage.


2011 ◽  
Vol 124 (2) ◽  
pp. 414-423 ◽  
Author(s):  
R. B. Hernández ◽  
M. Farina ◽  
B. P. Espósito ◽  
N. C. Souza-Pinto ◽  
F. Barbosa ◽  
...  

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