Linked Life Data

19672954

Source:http://linkedlifedata.com/resource/pubmed/id/19672954

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2009-10-19
pubmed:abstractText
Apoptosis can be modulated by K(+) and Ca(2+) inside the cell and/or in the extracellular milieu. In murine organotypic cultures, membrane potential-regulated Ca(2+) signaling through calcineurin phosphatase has a pivotal role in development and maturation of cerebellar granule cells (CGCs). P8 cultures were used to analyze the levels of expression of B cell lymphoma 2 (BCL2) protein, and, after particle-mediated gene transfer in CGCs, to study the posttranslational modifications of BCL2 fused to a fluorescent tag in response to a perturbation of K(+)/Ca(2+) homeostasis. There are no changes in Bcl2 mRNA after real time PCR, whereas the levels of the fusion protein (monitored by calculating the density of transfected CGCs under the fluorescence microscope) and of BCL2 (inWestern blotting) are increased. After using a series of agonists/antagonists for ion channels at the cell membrane or the endoplasmic reticulum (ER), and drugs affecting protein synthesis/degradation, accumulation of BCL2 was related to a reduction in posttranslational cleavage by macroautophagy. The ER functionally links the [K(+)](e) and [Ca(2+)](i) to the BCL2 content in CGCs along two different pathways. The first, triggered by elevated [K(+)](e) under conditions of immaturity, is independent of extracellular Ca(2+) and operates via IP3 channels. The second leads to influx of extracellular Ca(2+) following activation of ryanodine channels in the presence of physiological [K(+)](e), when CGCs are maintained in mature status. This study identifies novel mechanisms of neuroprotection in immature and mature CGCs involving the posttranslational regulation of BCL2.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1932-846X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
69
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
855-70
pubmed:meshHeading
pubmed-meshheading:19672954-Animals, pubmed-meshheading:19672954-Apoptosis, pubmed-meshheading:19672954-Autophagy, pubmed-meshheading:19672954-Blotting, Western, pubmed-meshheading:19672954-Calcium, pubmed-meshheading:19672954-Cell Survival, pubmed-meshheading:19672954-Cerebellum, pubmed-meshheading:19672954-Cyclic AMP Response Element-Binding Protein, pubmed-meshheading:19672954-Endoplasmic Reticulum, pubmed-meshheading:19672954-Fluorescent Antibody Technique, pubmed-meshheading:19672954-Gene Transfer Techniques, pubmed-meshheading:19672954-Image Processing, Computer-Assisted, pubmed-meshheading:19672954-Inositol 1,4,5-Trisphosphate Receptors, pubmed-meshheading:19672954-Membrane Potentials, pubmed-meshheading:19672954-Mice, pubmed-meshheading:19672954-Microscopy, Confocal, pubmed-meshheading:19672954-Neurons, pubmed-meshheading:19672954-Organ Culture Techniques, pubmed-meshheading:19672954-Phosphorylation, pubmed-meshheading:19672954-Potassium, pubmed-meshheading:19672954-Protein Processing, Post-Translational, pubmed-meshheading:19672954-Proto-Oncogene Proteins, pubmed-meshheading:19672954-RNA, Messenger, pubmed-meshheading:19672954-Reverse Transcriptase Polymerase Chain Reaction
pubmed:year
2009
pubmed:articleTitle
Posttranslational regulation of BCL2 levels in cerebellar granule cells: A mechanism of neuronal survival.
pubmed:affiliation
Dipartimento di Morfofisiologia Veterinaria, Università degli Studi di Torino, Italy. laura.lossi@unito.it
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't