Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study investigates whether insulin (a differentiation factor for lens epithelial cells) acts as a survival factor. In the absence of insulin, 6-day embryonic chicken lens epithelial explants undergo apoptosis as shown by changes in cell morphology, DNA fragmentation, and loss of trypan blue exclusion. Insulin inhibits these changes and promotes survival of the cells. Aurintricarboxylic acid suppresses the apoptosis of lens explants. In contrast to 6-day embryonic explants, 19-day embryonic explants survive in the absence of insulin, presumably due to an endogenous survival factor. To explore the mechanism of the action of insulin as a survival factor for 6-day embryonic lens explants, we compared the pattern of cell cycle markers (c-fos, c-jun, c-myc, p53, histone H3, thymidine kinase, and cyclin B) in both apoptotic and differentiating lens explants. In the presence of insulin, the expression of c-fos and c-jun was down-regulated after an initial induction. Expression of these genes was also induced in the absence of insulin, but mRNA levels remained elevated as the cells underwent apoptosis. In contrast, expression of c-myc, p53, histone H3, thymidine kinase, and cyclin B showed only minor differences in differentiating and apoptotic cells. Since c-fos and c-jun have been shown to play a role in apoptosis in other cell types, the ability of insulin to regulate expression of these genes may be central to its ability to act as a survival factor for lens epithelial cells.
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PMID:Insulin regulates expression of c-fos and c-jun and suppresses apoptosis of lens epithelial cells. 854 23

The ability to direct expression of genes to astrocytes in mice has been one of the major motivators of transcriptional analyses of the glial fibrillary acidic protein (GFAP) gene. Another has been the possibility of discovering signaling pathways that operate during development, disease, and injury-all states that increase GFAP gene activity-by identifying and working back from the responsible DNA elements. Here we review studies in both these areas and provide practical guidelines for the construction and analysis of GFAP transgenes. Analyses of the GFAP promoter from cell transfection experiments are summarized to provide background information for the studies in transgenics. Another section provides practical information on the construction and analysis of transgenic mice, with particular reference to GFAP transgenes. The survey of analyses of GFAP transcription elements in transgenic mice reveals that a segment of about 2 kb of the 5'-flanking region of the gene is sufficient to direct reporter gene activity to astrocytes with high specificity. This segment also supports a response to brain injury by upregulation of the activity. Developmentally, the transgene activity is seen by e12.5, several days earlier than GFAP protein or mRNA has been detected. GFAP transcription control regions have already been used to express several proteins in astrocytes to evaluate their biological effects. These proteins include IL-3, IL-6, TGF-beta1, the HIV envelop protein gp120, the MHC Class I Db protein, somatosatin, CNTF, and the herpes simplex virus thymidine kinase. In the future many other GFAP transgenes are expected to be produced, with increasing knowledge of the GFAP regulatory elements promising greater sophistication through promoters that can be regulated, have higher activity, and target activity to particular brain regions.
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PMID:GFAP Transgenic Mice 895 47