Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.17 (MMP-3)
 3,419 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have examined the hypothesis that neuronal programmed cell death requires a genetic program; we used a model wherein rat sympathetic neurons maintained in vitro are deprived of NGF and subsequently undergo apoptosis. To evaluate gene expression potentially necessary for this process, we used a PCR-based technique and in situ hybridization; patterns of general gene repression and selective gene induction were identified in NGF-deprived neurons. A temporal cascade of induced genes included "immediate early genes," which were remarkable in that their induction occurred hours after the initial stimulus of NGF removal and the synthesis of some required ongoing protein synthesis. The cascade also included the cell cycle gene c-myb and the genes encoding the extracellular matrix proteases transin and collagenase. Concurrent in situ hybridization and nuclear staining revealed that while c-jun was induced in most neurons, c-fos induction was restricted to neurons undergoing chromatin condensation, a hallmark of apoptosis. To evaluate the functional role of the proteins encoded by these genes, neutralizing antibodies were injected into neurons. Antibodies specific for either c-Jun or the Fos family (c-Fos, Fos B, Fra-1, and Fra-2) protected NGF-deprived neurons from apoptosis, whereas antibodies specific for Jun B, Jun D, or three nonimmune antibody preparations had no protective effect. Because these induced genes encode proteins ranging from a transcription factor necessary for death to proteases likely involved in tissue remodeling concurrent with death, these data may outline a genetic program responsible for neuronal programmed cell death.
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PMID:Altered gene expression in neurons during programmed cell death: identification of c-jun as necessary for neuronal apoptosis. 779 22

Cerebellar granule cells maintained in medium containing serum and 25 mM potassium undergo an apoptotic death within 96 hr when switched to serum-free medium with 5 mM potassium. Because large numbers of apparently homogeneous neurons can be obtained, this represents a potentially useful model of neuronal programmed cell death (PCD). Analysis of the time course and extent of death after removal of either serum or K+ alone demonstrated that a fast-dying (T(1/2) = 4 hr) population (20%) responded to serum deprivation, whereas a slow-dying (T(1/2) = 25 hr) population (80%) died in response to K+ deprivation. Taking advantage of the complete death after removing both K+ and serum, changes in metabolic events and mRNA levels were analyzed in this model. Glucose uptake, protein synthesis, and RNA synthesis fell to <35% of control by 9 hr after potassium/serum deprivation, a time when 85% of the cells were still viable. The pattern of the fall in these metabolic parameters was similar to that reported for trophic factor-deprived sympathetic neurons. Most mRNAs decreased markedly after K+/serum deprivation. Levels of c-jun mRNA increased fivefold in potassium/serum-deprived granule cells; c-jun is required for cell death of sympathetic neurons. mRNA levels of cyclin D1, c-myb, collagenase, and transin remained relatively constant in potassium/serum-deprived granule cells. These data demonstrate the existence of two populations of granule cells with respect to cell death and define common metabolic and genetic events involved in neuronal PCD.
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PMID:Metabolic and genetic analyses of apoptosis in potassium/serum-deprived rat cerebellar granule cells. 892 4