The neuroprotective effects of 2-APB in rats with experimentally- -induced severe acute pancreatitis (original) (raw)
Related papers
Neurotoxicity Research, 2003
While the role of apoptosis in neuronal injury is continually being redefined , approaches to intervene in the progression of apoptotic injury have been documented to provide neuroprotection against a variety of insults. The present studies were undertaken to systematically study the effects of certain neuroprotective agents against neuronal apoptosis mediated by staurosporine (ST). ST (0.01-5 μM) produced a dose-related apoptotic injury (as characterized by cellular morphology, 'Comet' assay analysis [single cell gel electrophoresis] and caspase-3 activation) in primary cultures of forebrain neurons. ST significantly increased caspase-3 activity. The NMDA receptor subtype non-selective antagonist dizocilpine [(+) MK-801; 0.1-50 μM] and a novel sodium channel blocker RS100642 (1.0-250 μM) had no significant effects against ST-induced neurotoxicity. Conversely, NR2B-selective NMDA receptor antagonists CGX-1007 (0.01-50 μM) and ifenprodil (0.01-50 μM) provided dose-dependent neuroprotection against ST-induced neurotoxicity (as measured by neuronal viability and comet assay analysis). CGX-1007 had no significant effect on ST-induced caspase-3 activity; however, ifenprodil did block activation of caspase-3. These studies demonstrate that NR2B NMDA receptor antagonists are anti-apoptotic and may mediate their action via mechanism(s) that are dependent or independent of caspase-3 activation.
Efficacy of 2-APB (2-Aminoethyldiphenylborate) in Rescuing Neurons After Soman-Induced Brain Injury
2005
Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188),
BCL-2 Inhibits Death of Central Neural Cells Induced by Multiple Agents
Proceedings of the National Academy of Sciences, 1993
The protooncogene bcl-2, which has been implicated in B-cell lymphoma development, inhibits apoptosis due to growth factor withdrawal in some, but not all, hematopoietic cells. Recently we found that bcl-2 also inhibits apoptosis in PC12 pheochromocytoma cells. We now report that bcl-2 inhibits the death of a central neural cell line due to serum and growth factor withdrawal, the calcium ionophore A23187, glucose withdrawal, membrane peroxidation, and, in some cases, free radical-induced damage. This broad range of protective effects of BCL-2 protein suggests that BCL-2 may interact with a central step in neural cell death. Measurements of intracellular free calcium suggest that BCL-2 alters the transduction of neural death signals at a point distal to the rise in intracellular free calcium.
Neurorx, 2004
It has been increasingly recognized that cell death phenotypes and their molecular mechanisms are highly diverse. Necrosis is no longer considered a single entity, passively mediated by energy failure. Moreover, caspase-dependent apoptosis is not the only pathway involved in programmed cell death or even the only apoptotic mechanism. Recent experimental work emphasizes the diverse and interrelated nature of cell death mechanisms. Thus, there are both caspase-dependent and caspase-independent forms of apoptosis, which may differ morphologically as well as mechanistically. There are also necrotic-like phenotypes that requirede novo protein synthesis and are, therefore, forms of programmed cell death. In addition, forms of cell death showing certain morphological features of both necrosis and apoptosis have been identified, leading to the term aponecrosis. Considerable experimental evidence also shows that modulation of one form of cell death may lead to another. Together, these observations underscore the need to substantially revise our conceptions about neuroprotection strategies. Use of multiple treatments that target different cell death cascades, or single agents that moderate multiple cell death pathways, is likely to lead to more effective neuroprotection for clinical disorders.
Apoptosis and Alzheimer's disease
Journal of Neural Transmission, 2000
Cell death by apoptosis comprises a sequence of events leading to the activation of caspases. Caspases execute the fragmentation of the cellular protein and DNA, ultimately, leading to disintegration of the cell. Apoptosis is a tightly regulated physiological mechanism that is crucial during development and thereafter for the maintenance of the balance between cell division and cell death. In contrast to the rather smoothly operating cell death machinery of apoptosis, necrosis is caused by insults leading to the rapid disruption of cellular metabolism and the non-physiological disintegration of the cells. Frequently, toxic events or traumatic challenges trigger the rapid necrotic cell death. Apoptosis and necrosis can be discriminated by a number of morphological and biochemical characteristics. To describe the specific mechanisms of cell death occurring during neurodegenerative disorders, such as Alzheimer's disease (AD), many investigations, both in vivo and in vitro, have attempted to label the particular pathway of cell death either as apoptosis or as necrosis. The elucidation of the mechanism of cell death promises to identify novel pharmaceutical targets for the prevention and therapy of AD. Apoptotic and necrotic cells can be found in AD tissue, and both pathways can be mimicked employing a variety of models systems of AD-associated nerve cell degeneration. Certain genes that are linked to familial AD may render neurons more vulnerable to apoptosis, but it has to be stressed that the vast majority of AD cases are sporadic and not strictly genetically determined. Apoptosis and necrosis may overlap, may sequentially occur under certain conditions, and may not be detected unequivocally. In conclusion, on the basis of the presently available data it has to be stated that although many studies in vivo and in vitro favor apoptosis in AD, there is considerable evidence that a mixture of both events may contribute to neurodegeneration in AD and to its final pathology.
Anti-apoptosis therapy: A way of treating neural degeneration?
Current Biology, 1998
Many degenerative diseases involve apoptotic cell death-can they be treated with apoptosis inhibitors, while protecting the normal physiological function of the rescued cells? Reason for optimism comes from a recent study of mutant flies with an analogue of the human degenerative disease retinitis pigmentosa.
2002
Among the many regulatory steps in brain development is the process of elimination of differentiating neurons at certain stages of maturation through an intrinsic suicide program now widely known as apoptosis. Apoptosis may thus describe a cell death pathway utilized by many developing cells in the nervous system, but may also be activated as a consequence of acute or chronic pathological impulses. Such pathological impulses may include brain injury, cerebral hypoxia-ischemia and the potentials of selected drugs such as N-methyl D-aspartate (NMDA) receptor antagonists, GABA mimetics and ethanol. In recent years, there has been a great interest in mechanisms of cell death in the nervous system and apoptotic cell death has been implicated in many neurodegenerative diseases such as Alzheimer’s disease, amiotrophic lateral sclerosis, Parkinson’s disease and other central and peripheral nervous system disorders. Recent findings have evaluated the contribution of programmed cell death and...