Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuronal cell death in the embryonic brain was first recognized almost a century ago. Its significance for normal nervous system development and function has been a major focus of neuroscientific investigation ever since. Remarkable progress has been made in defining the cellular processes controlling neuronal cell death and studies performed over the last ten years have revealed extensive homology between the molecules regulating programmed cell death in Caenorhabditis elegans and apoptosis in mammalian cells. Targeted gene disruptions of members of the bcl-2 and caspase gene families have demonstrated particularly significant roles for bcl-x, bax, caspase-9 and caspase-3 in mammalian brain development. As expected from previous studies of synapse-bearing neurons and neurotrophic factors, reduced neuronal cell death in mice bearing mutations in key pro-apoptotic molecules resulted in increased numbers of neurons in a variety of neuronal subpopulations. However, targeted gene disruptions also demonstrated a heretofore underappreciated significance of neural precursor cell death and immature neuron death in nervous system development. Pathological activation of apoptotic death pathways may lead to neuroanatomic abnormalities and possibly to developmental disabilities.
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PMID:Apoptosis and brain development. 1175 20

Homozygous endothelin B receptor deficiency leads to congenital aganglionosis of the gut in rats and mice, equivalent to human Hirschsprung disease. Homozygous endothelin B receptor deficient rats (spotting lethal rats, sl/sl) are characterized not only by this developmental disorder of the enteric nervous system, which limits their life span to 3-4 weeks, but exhibit an increased rate of apoptosis in the dentate gyrus compared to wildtype (+/+) rats. Recently, endothelin B receptor deficient transgenic rescue rats (sl/sl, tg/tg) were created to further investigate the role of the endothelin B receptor in mature animals. Linkage of the human dopamine-beta-hydroxylase promoter to the rat endothelin B receptor gene and expression of this transgenic construct results in normal development of the enteric nervous system. We investigated the expression pattern of this transgenic construct in the brain by using reverse transcriptase polymerase chain reaction. Unexpectedly, transgene mRNA expression was not restricted to the brain stem where adrenergic and noradrenergic nuclei are known to be present but, in addition, was also detectable in hippocampus and cortex. Using in situ tailing technique, cleaved caspase-3 immunohistochemistry and analysis of hematoxylin-eosin-stained serial sections, we found that all studied transgenic animals were rescued from the increased rate of apoptosis in the dentate gyrus characteristic for non-transgenic sl/sl rats. This finding supports our previous observation that the endothelin B receptor might be an important regulatory element supporting cellular survival in the hippocampus during postnatal development. The endothelin B receptor deficient transgenic rescue rats used here are rescued from developmental disorders both in the gut and in the brain.
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PMID:Endothelin B receptor deficient transgenic rescue rats: a rescue phenomenon in the brain. 1502 12

Hypoxia is a consistent challenge for aquatic animals. It is a pressing environmental problem; hypoxia can cause cranial edema and ovarium dysfunction in fish. Although several studies have reported the effect of hypoxic insult to the visual system, the hypoxic effect on perinatal animals and in particular their offspring has yet to be elucidated. In this study, activated caspase-3 activity was investigated using immunohistochemistry in order to examine the perinatal hypoxic damage in offspring fish. Offspring were divided into groups based on different time points of sacrifice. This allowed assessment of ocular development for different age groups. The results indicated that perinatal hypoxia induced ocular developmental defects in the offspring. The defects took the form of trabecular cell death and fibre degeneration, corneal thinning and lens fibre derangement. A concomitant change in intraocular pressure was recorded by tonometer in the experimental animals compared with the controls. Further investigation should be initiated to develop strategies to prevent developmental disability due to perinatal hypoxia and to increase survivability of the offspring.
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PMID:Perinatal hypoxia induces anterior chamber changes in the eyes of offspring fish. 1769 1

Fetal alcohol syndrome is a neurological and developmental disorder caused by exposure of developing brain to ethanol. Administration of osmotin to rat pups reduced ethanol-induced apoptosis in cortical and hippocampal neurons. Osmotin, a plant protein, mitigated the ethanol-induced increases in cytochrome c, cleaved caspase-3, and PARP-1. Osmotin and ethanol reduced ethanol neurotoxicity both in vivo and in vitro by reducing the protein levels of cleaved caspase-3, intracellular [Ca(2+)]cyt, and mitochondrial transmembrane potential collapse, and also upregulated antiapoptotic Bcl-2 protein. Osmotin is a homolog of adiponectin, and it controls energy metabolism via phosphorylation. Adiponectin can protect hippocampal neurons against ethanol-induced apoptosis. Abrogation of signaling via receptors AdipoR1 or AdipoR2, by transfection with siRNAs, reduced the ability of osmotin and adiponectin to protect neurons against ethanol-induced neurodegeneration. Metformin, an activator of AMPK (adenosine monophosphate-activated protein kinase), increased whereas Compound C, an inhibitor of AMPK pathway, reduced the ability of osmotin and adiponectin to protect against ethanol-induced apoptosis. Osmotin exerted its neuroprotection via Bcl-2 family proteins and activation of AMPK signaling pathway. Modulation of AMPK pathways by osmotin, adiponectin, and metformin hold promise as a preventive therapy for fetal alcohol syndrome.
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PMID:Neuroprotective effect of osmotin against ethanol-induced apoptotic neurodegeneration in the developing rat brain. 2467 68