PubMed · 14092874
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
A M FOURNIER, P GUERIN. 1963. [APPENDICULAR LITHIASIS].. https://pubmed.ncbi.nlm.nih.gov/14092874/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Explore the source record for details and available documents.
Programmed cell death or apoptosis is a physiologically important process in neurogenesis wherein approximately 50% of the neurons apoptose during maturation of the nervous system. However, premature apoptosis and/or aberrations in apoptosis control contribute to the pathogenesis of a variety of neurological disorders including acute brain injury such as trauma, spinal cord injury, ischemic stroke and ischemia/reperfusion as well as chronic disease states such as Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, spinal muscular atrophy, and diabetic neuropathy. The current review will focus on two major topics, namely, the general concepts of our current understanding of the apoptosis death machinery, its mediators and regulation, and the relationship between aberrant apoptosis and genesis of neurodegenerative disorders. This knowledge of apoptosis mechanisms will underpin the basis for development of novel therapeutic strategies and treatment modalities that are directed at control of the neuronal apoptotic death program.
Programmed cell death and survival are controlled by complex pathways, with the anti-apoptotic proteins Bcl-2 and Bcl-X(L) and the pro-apoptotic proteins Bax and Bcl-X(S) being major regulators. Variations in the expression of Bcl-X(S) have been observed in leukemic cells from acute myeloid leukemia (AML) patients and correlated with clinical outcome, but the impact of Bcl-X(S) on molecular pathophysiological mechanisms and the potential role of Bcl-X(S) as a therapeutic target in AML are not yet defined. In order to analyze the functional relevance of Bcl-X(S) in AML, Bcl-X(S) was moderately (2-3 fold) overexpressed in the AML cell lines HL-60 and MO7e by transfection with a tetracycline-regulatable Bcl-X(S) expression system. Increased Bcl-X(S) did not change the rate of spontaneous apoptosis, chemosensitivity to ara-C, or cell cycle kinetics. Further analysis of this unexpected result revealed a compensatory transcriptional upregulation of endogenous anti-apoptotic Bcl-X(L) in MO7e and HL-60, and Bcl-2 in HL-60 cells resulting in increased protein levels. Bax levels were unchanged. Bcl-X(L) and Bcl-2 were found to heterodimerize with Bcl-X(S), thereby providing a possible explanation for the abrogation of its pro-apoptotic function. These results suggest the existence of a regulatory mechanism aimed to protect leukemic cells from pro-apoptotic stimuli.