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Biomedical subjects

R Bravo

Publications and source records attributed to R Bravo.

At least 145 records · Page 8Linked to original sources
PubMed1994

Biological activity of the growth factor-induced cytokine N51: structure-function analysis using N51/Interleukin-8 chimeric molecules.

The immediate-early gene N51/KC encodes a protein which following expression in the baculovirus system and purification to apparent homogeneity is able to induce chemotaxis and intracellular Ca2+ flux, to compete for 125I-labeled interleukin-8 (IL-8) binding, and upon iodination, to bind specifically to human neutrophils. The activity of N51/KC can be distinguished from that of IL-8 by a number of criteria. First, at equivalent concentrations, the specific binding of [125I]N51/KC to human neutrophils is about 10 times less than that of [125I]IL-8. Second, the competition studies of [125I]IL-8 with IL-8 define a single class of high-affinity receptors, while the presence of both a high- and a low-affinity class of receptors is defined by N51/KC. Third, although the changes in intracellular Ca2+ of fura-2/AM-preloaded human neutrophils elicited by N51/KC and IL-8 are similar, pretreatment of the cells with N51/KC did not result in a loss of response to a subsequent treatment with IL-8; in contrast, treatment with IL-8 did result in the subsequent desensitization to N51/KC. To further characterize N51/KC, mutants and hybrids of N51/KC and IL-8 were produced and analyzed for the ability to compete for [125I]IL-8 binding and elicit intracellular Ca2+ changes in human neutrophils. Two important observations came from these studies. First, the N51/IL-8I hybrid in which the N51/KC sequence between cysteines 2 and 3 (or first disulfide bond) is replaced by the corresponding sequence in IL-8 shows IL-8-like properties, indicating that this region is important for specific receptor recognition. Second, the N51 delta III and IL-8 delta III C-terminus deletion mutants were biologically inactive, but the hybrid molecules N51/IL-8III and IL-8/N51III, in which the C termini were exchanged, had biological activities similar to that of the wild-type molecules, demonstrating that the presence of the C terminus is essential for the biological activity of these chemokines but does not confer receptor specificity.

Amino Acid Sequence↗
PubMed1994

c-Fos-induced activation of a TATA-box-containing promoter involves direct contact with TATA-box-binding protein.

Transcriptional activation in eukaryotes involves protein-protein interactions between regulatory transcription factors and components of the basal transcription machinery. Here we show that c-Fos, but not a related protein, Fra-1, can bind the TATA-box-binding protein (TBP) both in vitro and in vivo and that c-Fos can also interact with the transcription factor IID complex. High-affinity binding to TBP requires c-Fos activation modules which cooperate to activate transcription. One of these activation modules contains a TBP-binding motif (TBM) which was identified through its homology to TBP-binding viral activators. This motif is required for transcriptional activation, as well as TBP binding. Domain swap experiments indicate that a domain containing the TBM can confer TBP binding on Fra-1 both in vitro and in vivo. In vivo activation experiments indicate that a GAL4-Fos fusion can activate a promoter bearing a GAL4 site linked to a TATA box but that this activity does not occur at high concentrations of GAL4-Fos. This inhibition (squelching) of c-Fos activity is relieved by the presence of excess TBP, indicating that TBP is a direct functional target of c-Fos. Removing the TBM from c-Fos severely abrogates activation of a promoter containing a TATA box but does not affect activation of a promoter driven only by an initiator element. Collectively, these results suggest that c-Fos is able to activate via two distinct mechanisms, only one of which requires contact with TBP. Since TBP binding is not exhibited by Fra-1, TBP-mediated activation may be one characteristic that discriminates the function of Fos-related proteins.

Adenovirus E1A Proteins↗
PubMed1994

NOT, a human immediate-early response gene closely related to the steroid/thyroid hormone receptor NAK1/TR3.

By analyzing the early genetic response of human T cells following mitogenic activation we have identified NOT, a member of the steroid/thyroid hormone family of receptors. NOT has all structural features of steroid/thyroid hormone receptors (C2C2 zinc-finger domain, ligand binding domain), but is rapidly and only very transiently expressed after cell activation, which is clearly at variance with classical steroid receptors such as glucocorticoid or estrogen receptors. NOT gene induction is independent of de novo protein synthesis, defining NOT as an immediate-early response gene. Short-lived NOT mRNA (4.2 kilobases) expression could be observed in vitro in a greater number of tissue types following activation by a variety of distinct stimuli. In vivo, NOT mRNA expression was detected exclusively in the brain, where a very strong signal was observed. By immunoblot analysis of human T cell lysates with NOT specific antisera two activation-dependent protein bands (66 and 59 kilodaltons) could be detected. NOT gene was localized to human chromosome 2q22-q23. Sequence comparison revealed that NOT is the human homolog of the murine NURR1 and rat RNR-1. Moreover NOT is closely related to NAK1/TR3, a previously identified human orphan steroid receptor. Several lines of evidence indicate that NOT and NAK1/TR3 form a distinct and exclusive subgroup of orphan steroid receptors, whose expression characteristics in vitro and in vivo resemble the expression of nonsteroid immediate-early transcription factors such as jun and fos. NOT and NAK1/TR3 thus may function as general coactivators of gene transcription rather than participate in the induction of specific target genes, as is the case with classical steroid receptors.

Amino Acid Sequence↗
PubMed1994

Developmental expression of the mouse c-rel proto-oncogene in hematopoietic organs.

We have studied the expression of the c-rel proto-oncogene during mouse embryonic development and adult animals using in situ hybridization and immunocytochemical analysis. c-rel transcripts were detected late in development with an expression pattern that parallels the emergence and diversification of hematopoietic cells. In the embryo, c-rel is expressed first in the mesoderm-derived hematopoietic cells of the liver and later also in other hematopoietic tissues such as thymus and spleen. This correlation between c-rel expression and places of hematopoietic infiltration is conserved in the postnatal period, with expression of c-rel mRNA in the medullary region of the thymus and in splenic B cell areas, including the marginal zone and the outer region of the periarterial sheath. High levels of c-rel transcripts were also detected in the splenic germinal centers, lymph nodes and Peyer's patches. Using double immunofluorescence and cell preparations from different embryonic and adult hematopoietic organs, we have defined the pattern and cell types of c-rel expression in different hematopoietic cell lineages and in the stromal cell content of the thymus. By using electrophoretic mobility shift assays, we have also correlated c-Rel expression in spleen with kappa B-binding activity in the form of c-Rel/p50 and c-Rel/p52 heterodimers. The timing and pattern of expression of the c-rel proto-oncogene in the different cell lineages suggest that temporally regulated changes in c-Rel expression may be required for vertebrate hematopoiesis.

Animals↗
PubMed1994

Isolation and characterization of c-fos recombinant baculovirus.

The use of the baculovirus system to produce recombinant proteins is based on the high level of protein production and the possibility to obtain, in Spodoptera frugiperda insect cells, recombinant proteins with the post-translational modifications found in the native proteins. Here we describe the isolation and characterization of a recombinant baculovirus containing the mouse c-fos gene. The c-fos cDNA was subcloned into the pVL1392 baculovirus transfer vector. The recombinant plasmid (pVL1392.fos) was introduced into Sf9 insect cells by co-transfection with viral wild-type DNA. Upon selection and characterization of a viral recombinant clone, Sf9 cells were infected with this virus stock and the cFos protein expression was detected by immunological methods using an anti-cFos polyclonal antiserum.

Animals↗
PubMed1994

Constitutive and inducible Rel/NF-kappa B activities in mouse thymus and spleen.

We have studied the expression of members of the rel family of transcription factors and ikba in mouse thymus and spleen by in situ hybridization. Our results show that the rel genes have different temporal and spatial patterns of expression suggesting distinct roles in these lymphoid tissues. The Rel/NF-kappa B proteins and I kappa B alpha in thymus and spleen were also analysed by Western blotting and electrophoretic mobility shift assays. Although RelB protein is present at significantly lower levels in thymus and spleen extracts when compared to RelA, in both tissues the predominant kappa B-binding activity consists of p50/RelB and p52/RelB heterodimers and only very little binding of RelA-containing complexes to kappa B sites was detected. Significant binding of c-Rel complexes was only found in spleen extracts. Treatment of thymus and spleen extracts with deoxycholate (DOC), however, results in a strong increase in binding to kappa B sites of both RelA and c-Rel complexes. In contrast, binding of RelB complexes is not induced after DOC treatment. Our results suggest a differential role of Rel/NF-kappa B complexes in mouse thymus and spleen with RelB heterodimers representing the constitutive kappa B-binding activity, whereas RelA and c-Rel complexes most likely are involved in inducible kappa B-binding and gene activation.

Animals↗
PubMed1994

Rearrangement and altered expression of the NFKB-2 gene in human cutaneous T-lymphoma cells.

The NF-kappa b/Rel and I kappa B proteins are important regulators of lymphocyte activation and gene expression. We have identified a rearrangement of the NFKB-2 gene in the HUT 78 human cutaneous T-cell leukemia (CTCL) line, cDNA and genomic DNA sequence predicted the presence of a truncated 80 kD NFKB-2 precursor protein (p80HT), instead of the normal p100 protein. No wild-type allele was identified. Elevated levels of two aberrantly sized RNAs were detected, and high levels of p80HT and processed p52 protein were present in HUT 78 cell nuclei. The p52 protein bound to a palindromic kappa B DNA motif, however p80HT did not. Rearrangement of the NFKB-2 gene was also detected in DNA from two patients with CTCL. Rearrangement and overexpression of the NFKB-2 gene may contribute to the genesis of a subset of T-cell malignancies.

Amino Acid Sequence↗
PubMed1994

Regulation of Fra-1 and Fra-2 phosphorylation differs during the cell cycle of fibroblasts and phosphorylation in vitro by MAP kinase affects DNA binding activity.

The Fos family of transcription factors, c-Fos, FosB, Fra-1 and Fra-2, are rapidly induced in quiescent fibroblasts following serum or growth factor stimulation. The Fos proteins show distinct patterns of expression during cell growth with only Fra-1 and Fra-2 maintained at significant levels in growing cells, suggesting that the different family members direct unique functions for cell growth. Post-translational modification of Fos proteins has been observed following serum stimulation, which may allow an additional level of regulation. Our studies show that the synthesis and post-translational modification of Fra-1 and Fra-2 in Swiss 3T3 cells is serum-dependent during G1 following the transition from G0 and during asynchronous growth but is serum-independent during S phase and mitosis. Post-translational modification of Fra-1 and Fra-2 causes a significant shift in their gel mobility which is eliminated by alkaline phosphatase treatment. Several kinases can phosphorylate Fra-1 and Fra-2 in vitro, including cAMP-dependent kinase (PKA), protein kinase C (PKC), cyclin-dependent kinase 1-cdc2 (cdc2), and mitogen activated protein (MAP) kinase. From these, MAP kinase is the only one that causes a shift in gel mobility similar to that observed in vivo. One dimensional phosphopeptide maps of Fra-1 and Fra-2 phosphorylated by MAP kinase in vitro are similar to those of in vivo labeled Fra-1 and Fra-2, suggesting that MAP kinase may also phosphorylate Fra-1 and Fra-2 in vivo. We have also determined that phosphorylation of Fra-1 and Fra-2 by MAP kinase increases their DNA binding activity.

3T3 Cells↗
PubMed1993

A sub-set of immediate early mRNAs induced by tumor necrosis factor-alpha during cellular cytotoxic and non-cytotoxic responses.

TNF-alpha is a multifunctional cytokine which is cytotoxic for some cell lines. In order to characterize the early genomic response to TNF-alpha, we have analyzed the induction of a sub-set of serum-inducible immediate early genes in WEHI-S and L929 fibrosarcoma cell lines, which are sensitive to TNF-alpha, and in the 3T3-LI pre-adipocytic cell line, which is resistant to TNF-alpha cytotoxicity. Among 77 immediate early mRNAs screened by dot blot and/or Northern blot analyses, the expression of 23 mRNAs was found to be induced by TNF-alpha. Ten of these mRNAs encode proteins known to function as pro-inflammatory cytokines or transcription factors, while 13 others have as yet uncharacterized activities. The magnitude of c-fos induction by TNF-alpha inversely correlated with cell-type-specific cytotoxicity. Rapid and transient mRNA responses were observed in the TNF-alpha-resistant cells, whereas a slower and more persistent response was characteristic for TNF-alpha-sensitive cells. The prolonged induction of immediate early mRNAs may contribute to TNF-alpha-induced cellular cytotoxic responses.

Animals↗
PubMed1993

Differential time course and spatial expression of Fos, Jun, and Krox-24 proteins in spinal cord of rats undergoing subacute or chronic somatic inflammation.

We have used the evoked expression of both immediate early gene (IEG)-encoded proteins (Krox-24, c-Fos, Fos B, Jun D, Jun B, c-Jun), and dynorphin to monitor sensory processing in the spinal cords of rats undergoing subacute or chronic somatic inflammation (i.e., subcutaneous inflammation of the plantar foot and monoarthritis, respectively). Behavioral and immunocytochemical approaches were conducted in parallel up to 15 weeks postinjection in order to detect possible relationships between clinical evolution and spatiotemporal pattern of IEG-encoded protein expression. Each disease had specific characteristics both in terms of their clinical evolution and pattern of evoked protein expression. All IEG proteins were expressed in both cases. Most of the staining was observed in both the superficial layers of the dorsal horn and deep dorsal horn (laminae V-VII and X). Monoarthritis was distinguished by a high level of total protein expression. Staining was especially dense in the deep dorsal horn. More labelled cells were observed at 1-2 days and at 2 weeks postinjection, corresponding to the initiation and progressive phases of the disease, respectively. Subcutaneous inflammation was characterized by a moderate level of total IEG expression. More labelled cells were observed in the first day following injection. It is the relative degree of expression of each IEG-encoded protein with regard to the others that characterized the progression of the diseases. Early stages of the diseases coincided with the expression of all Fos and Jun proteins, while late stages showed an increase in Jun D and Fos B involvement; Krox-24 was induced mostly during the early phases and/or periods of paroxysm of the diseases. Persistent stimulation was characterized by a predominant expression in deep versus superficial layers of the dorsal horn. Evoked expression of c-Jun in motoneurons was only observed in monoarthritis. The peak of dynorphin expression was late in regard to both the induction of inflammation and period of maximal IEG-encoded protein expression. The present work indicates that the neural processing that takes place during progression of these diseases can be monitored well at the spinal cord level by using the expression of an array of IEG-encoded proteins. Study of long term evolutive diseases and especially those that evolve into chronicity can largely benefit from such an approach.

Acute Disease↗
PubMed1993

JUN, FOS, KROX, and CREB transcription factor proteins in the rat cortex: basal expression and induction by spreading depression and epileptic seizures.

The expression of the nuclear c-JUN, JUN B, JUN D, c-FOS, FOS B, KROX-24, and CREB transcription factors was investigated in the cortex of adult rats by immunocytochemistry. The expression patterns were studied in untreated rats and up to 24 hours following topical application of 1 M KCl to the cortical surface (KCl) or i.v. injection of bicuculline (BIC). Topical KCl induced cortical spreading depression and systemic injection of bicuculline evoked generalized tonic-clonic seizures. In untreated rats, JUN B, c-FOS, and FOS B were expressed in a small number of neurons in the piriform, perirhinal, entorhinal, and insular cortex and in layers II, III, and VI of all neocortical areas. In contrast, c-JUN, JUN D, and KROX-24 were expressed in all cortical layers but with different intensities of immunoreactivity (IR): c-JUN-IR was generally weak and predominantly present in layers II, III, and VI. JUN D-IR was equally strong in all layers. KROX-24 showed a prominent expression in layers II, IV, and VI. The CREB protein exhibited a slight preponderance in layer II and piriform cortex. Following KCl or BIC, a strong induction was seen for c-FOS, JUN B, and KROX-24, whereas c-JUN, JUN D, and FOS B showed only a moderate increase compared to basal levels. Changes of CREB-IR could not be detected. The localization of induced JUN, FOS, and KROX proteins reflected the pattern of labelling in untreated animals but demonstrated a higher intensity of labelling and an increased number of immunoreactive nuclei. The intensity and persistence of IR as well as the number of labelled cells following BIC exceeded those following KCl. Following BIC, increased levels of FOS B and JUN D were still present after 24 hours. Counterstaining with cresyl-violet and GFAP, a marker for astrocytes, revealed that JUN, FOS, and KROX proteins were expressed in neurons but not in glial cell populations. The present data demonstrate that CREB, JUN, FOS, and KROX transcription factors exhibit a layer-specific expression in the cerebral cortex with only slight area-specific differences both in untreated rats and following stimulation with KCl and BIC. The expression of transcription factor proteins indicate complex molecular genetic changes in cortical neurons due to pathophysiological events such as seizure activity and spreading depression.

Activating Transcription Factor 1↗
PubMed1993

Spatiotemporal induction of immediate early genes in the rat brain after limbic seizures: effects of NMDA receptor antagonist MK-801.

Fos, jun and krox belong to multigene families coding for transcription factors. These cellular immediate early genes (IEGs) are thought to be involved in coupling neuronal excitation to changes of target gene expression. Immunocytochemistry with specific antisera was used to assess regional levels of six IEG-encoded proteins (c-Fos, Fos B, Krox-24, c-Jun, Jun B, Jun D) in the rat forebrain after kainic acid-induced limbic seizures. The results demonstrate a complex spatial pattern of IEG induction and/or suppression in limbic and non-limbic structures. The sequence of induction within hippocampal subpopulations was identical for all IEGs investigated, following the order dentate gyrus, CA1 and CA3, and irrespective of different temporal profiles for individual transcription factors. Since Fos and Jun proteins act via homo- and heterodimer complexes at specific DNA sites, our data imply that the postictal combinatorial changes of these dimers allow a sequential and differential regulation of target gene expression in specific forebrain regions. Pretreatment with the non-competitive NMDA receptor antagonist MK-801 did not affect kainate-induced expression of IEGs in the limbic system, indicating that IEG induction in these regions is mediated by high-affinity kainate and AMPA receptors rather than NMDA receptors. In contrast, MK-801 abolished IEG induction in the somatosensory cortex and striatum, suggesting that IEG expression in non-limbic neurons occurs transsynaptically and is mediated by NMDA receptors.

Animals↗
PubMed1993

Long-lasting increase of nitric oxide synthase immunoreactivity, NADPH-diaphorase reaction and c-JUN co-expression in rat dorsal root ganglion neurons following sciatic nerve transection.

Changes of NADPH-diaphorase reaction (NDP) and nitric oxide synthase immunoreactivity (NOS-IR) in neurons of dorsal root ganglia (DRG) were investigated following transection and ligation of rat sciatic nerve. In untreated rats, 2.7% of L4/L5 DRG neurons were labelled by NDP. After 3 days, intensity of NDP and number of labelled neurons increased and reached a maximal level between 10 and 20 days in 26.8% neurons which persisted up to 50 days. After 150 days, 8.7% of DRG neurons were still labelled. In contralateral L4/L5 DRG, but not L1 and T10 DRG, the number but not the intensity of NDP labelled neurons slightly increased between 10 and 50 days. The patterns of NOS-IR and NDP were congruent. Ipsilaterally, 76% to 92% of NDP neurons showed co-expression with the c-JUN transcription factor which is supposed to play a crucial role in the regeneration process. NDP accumulated in the peripheral nerve stump and was increased in the superficial dorsal horn between 10 and 30 days, whereas motoneurons were not labelled by NOS and NDP.

Amino Acid Oxidoreductases↗
PubMed1993

Expression of JUN, KROX, and CREB transcription factors in goldfish and rat retinal ganglion cells following optic nerve lesion is related to axonal sprouting.

Goldfish and rat optic nerves were cut and crushed, respectively, and the expression of the transcription factor proteins c-JUN, JUN B, JUN D, c-FOS, FOS B, KROX-24, and CREB was investigated in retinal ganglion cells (RGCs) by immunocytochemistry. Immunoreactivities (IRs) were followed up to 350 days in the goldfish and up to 22 days in the rat. In RGCs of untreated goldfish and rats, all JUN, FOS, and KROX proteins were absent whereas CREB was constitutively expressed. After optic nerve cut in goldfish, a JUN-like immunoreactivity (JUN-IR) appeared in a small number of RGCs of central retina after 24 h, reached a maximum within 5 days, declined after 30 days, and was on a half-maximal level after 50 days. Between 100 and 200 days, JUN-IR was only visible in a few RGCs and was completely absent after 350 days. Specific antibodies against c-JUN, JUN B, and JUN D gave no distinct immunoreactive signal. Thus, we could not determine which member of the JUN family contributed to the JUN-IR. The expression of CREB declined after 5 days. The number of CREB-labeled RGCs was reduced (not significant) and the intensity of labeling faded out. After 50 days, CREB-IR had returned to basal level. c-FOS, FOS B, and KROX-24 could not be detected in goldfish RGCs following optic nerve cut. After optic nerve crush in the rat, c-JUN, JUN D, and KROX-24 appeared in a substantial number of RGCs after 24 h, had a maximal expression after 5 days, and strongly declined after 8 days. c-JUN and KROX-24 were completely absent after 22 days whereas JUN D was still present in a few rat RGCs. The number of CREB-labeled RGCs decreased after 5 days and had declined by 50% after 22 days. Expression of JUN B, c-FOS, FOS B could not be detected in rat RGCs after optic nerve crush. Our data demonstrate that the decrease of CREB and the increase of JUN and KROX-24 transcription factors precedes and parallels both the alteration of de novo protein synthesis and the axonal sprouting, which are long lasting in goldfish and transient in rat.

Animals↗
PubMed1993

Colocalisation and covariation of c-JUN transcription factor with galanin in primary afferent neurons and with CGRP in spinal motoneurons following transection of rat sciatic nerve.

The expression of galanin (GAL) in L5 dorsal root ganglia (DRG) and calcitonin gene-related peptide (CGRP) in motoneurons (MN) of lumbar spinal cord and their colocalisation with the nuclear c-JUN protein was investigated by immunocytochemistry following transection of rat sciatic nerve. Expression of c-JUN in L5 DRG neurons increased 10 h following transection. Between 24 h and 10 days 64%-72% of all neurons were labelled. After 50 and 150 days, the end of the observation period, 62% and 27%, respectively, of neurons were labelled by c-JUN. Expression of GAL started after 24 h, reached a maximum between 2 and 10 days in 40-50% of all neurons and persisted in 37% up to 50 days. After 150 days, GAL-IR had returned to basal levels. Between 24 h and 150 days, 75%-86% of all GAL positive neurons showed a nuclear c-JUN immunoreactivity, the maximal number was visible between 2 and 10 days. After 30 days, small diameter neurons showed a slightly increased colocalisation of GAL and c-JUN compared to large diameter neurons. In motoneurons (MN) of lumbar spinal cord of untreated rats, c-JUN was predominantly visible in small diameter MN. The number of c-JUN labelled MN raised 15 h following sciatic nerve transection in both small and large diameter MN. It reached its maximum after 2 days and declined after 40 days. CGRP showed basal expression exclusively in large MN. Its expression raised after 20 h, showed a maximum after 48 h and returned to control levels after 20 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

The KROX-20 transcription factor in the rat central and peripheral nervous systems: novel expression pattern of an immediate early gene-encoded protein.

The KROX-20 protein (also termed EGR-2) is encoded by an immediate early gene cloned by cross-hybridization to the Drosophila melanogaster Krüppel gene. It belongs to a class of transcription factors with zinc finger motifs and binding activity to a transcriptional regulatory DNA element termed the early growth response consensus sequence. In the present study the temporospatial expression of KROX-20 was investigated in the central and peripheral nervous systems of normal rats and after various stimuli known to induce immediate early genes, including epileptic seizures, axotomy, pharmacological treatment with glutamate and alpha-adrenergic receptor antagonists, and peripheral noxious stimulation. Immunocytochemistry was performed with a specific polyclonal antiserum generated against a fusion protein containing KROX-20 sequences. In the central nervous system, KROX-20 protein demonstrated distinct constitutive nuclear expression in specific neuronal subpopulations of the cortex, septum, amygdala, olfactory bulb and hypothalamus. In addition, distinct cytoplasmic immunoreactivity was present in spinal and medullary motoneurons, dorsal root ganglion neurons and a few neuronal cell populations of midbrain and forebrain. In the CNS, KROX-20 was only induced by bicuculline-induced epileptic seizures. Topographically, the postictal increase of KROX-20 levels was restricted to areas with constitutive expression, such as cerebral cortex, fornix and amygdala. Induction of KROX-20 peaked at 4-8 h after onset of seizure activity. No increase in immunoreactivity was observed in the hippocampus, the brain region most severely affected by bicuculline-induced seizures. Transection of central and peripheral nerve fibers did not result in KROX-20 induction in axotomized neurons. However, KROX-20 was induced in Schwann-like cells after transection of the sciatic nerve. In contrast to KROX-20, KROX-24, a related transcription factor of the zinc finger family, was markedly induced in hippocampal and spinal neurons following seizures and peripheral noxious stimulation, respectively, as well as in CNS neurons following axotomy. Our data indicate that KROX-20 represents an immediately early gene product with basal expression in selected neuronal populations of the nervous system and a restricted inducibility after intentional stimuli.

Animals↗