Biomedical subjects

D Hevroni

Publications and source records attributed to D Hevroni.

7 recordsLinked to original sources

PubMed1998

Hippocampal plasticity involves extensive gene induction and multiple cellular mechanisms.

Long-term plasticity of the central nervous system (CNS) involves induction of a set of genes whose identity is incompletely characterized. To identify candidate plasticity-related genes (CPGs), we conducted an exhaustive screen for genes that undergo induction or downregulation in the hippocampus dentate gyrus (DG) following animal treatment with the potent glutamate analog, kainate. The screen yielded 362 upregulated CPGs and 41 downregulated transcripts (dCPGs). Of these, 66 CPGs and 5 dCPGs are known genes that encode for a variety of signal transduction proteins, transcription factors, and structural proteins. Seven novel CPGs predict the following putative functions: cpg2--a dystrophin-like cytoskeletal protein; cpg4--a heat-shock protein: cpg16--a protein kinase; cpg20--a transcription factor; cpg21--a dual-specificity MAP-kinase phosphatase; and cpg30 and cpg38--two new seven-transmembrane domain receptors. Experiments performed in vitro and with cultured hippocampal cells confirmed the ability of the cpg-21 product to inactivate the MAP-kinase. To test relevance to neural plasticity, 66 CPGs were tested for induction by stimuli producing long-term potentiation (LTP). Approximately one-fourth of the genes examined were upregulated by LTP. These results indicate that an extensive genetic response is induced in mammalian brain after glutamate receptor activation, and imply that a significant proportion of this activity is coinduced by LTP. Based on the identified CPGs, it is conceivable that multiple cellular mechanisms underlie long-term plasticity of the nervous system.

Amino Acid Sequence↗

PubMed1997

Neuritin: a gene induced by neural activity and neurotrophins that promotes neuritogenesis.

Neural activity and neurotrophins induce synaptic remodeling in part by altering gene expression. A cDNA encoding a glycosylphoshatidylinositol-anchored protein was identified by screening for hippocampal genes that are induced by neural activity. This molecule, named neuritin, is expressed in postmitotic-differentiating neurons of the developing nervous system and neuronal structures associated with plasticity in the adult. Neuritin message is induced by neuronal activity and by the activity-regulated neurotrophins BDNF and NT-3. Purified recombinant neuritin promotes neurite outgrowth and arborization in primary embryonic hippocampal and cortical cultures. These data implicate neuritin as a downstream effector of activity-induced neurite outgrowth.

Amino Acid Sequence↗

PubMed1993

Numerous candidate plasticity-related genes revealed by differential cDNA cloning.

Plasticity is a property of the nervous system that allows it to modify its response to an altered input. This capacity for change suggests that there are molecular mechanisms in neurons that can couple stimuli to long-term alterations in phenotype. Neuronal excitation elicits rapid transcriptional activation of several immediate-early genes, for example c-fos, c-jun and zif268. Many immediate-early genes encode transcription factors that control expression of downstream genes whose products are believed to bring about long-term plastic changes. Here we use a highly sensitive differential complementary DNA cloning procedure to identify genes that may participate in long-term plasticity. We cloned 52 cDNAs of genes induced by the glutamate analogue kainate in the hippocampus dentate gyrus. The number of these candidate plasticity-related genes (CPGs) is estimated to be 500-1,000. One of the cloned CPGs (16C8), encoding a protease inhibitor, is induced by a stimulus producing long-term potentiation and during dentate gyrus development; a second, cpg1, is dependent on activation of the NMDA (N-methyl-D-aspartate) receptor for induction and encodes a new small, dentate-gyrus-specific protein. Seventeen of the cloned CPGs encode known proteins, including six suggesting that strong neuronal activation leads to de novo synthesis of vesicular and other synaptic components.

Amino Acid Sequence↗

PubMed1988

Bypass and termination at apurinic sites during replication of single-stranded DNA in vitro: a model for apurinic site mutagenesis.

Mutations produced in Escherichia coli by apurinic sites are believed to arise via SOS-assisted translesion replication. Analysis of replication products synthesized on depurinated single-stranded DNA by DNA polymerase III holoenzyme revealed that apurinic sites frequently blocked in vitro replication. Bypass frequency of an apurinic site was estimated to be 10-15%. Direct evidence for replicative bypass was obtained in a complete single-stranded----replicative form replication system containing DNA polymerase III holoenzyme, single-stranded DNA binding protein, DNA polymerase I, and DNa ligase, by demonstrating the sensitivity of fully replicated products to the apurinic endonuclease activity of E. coli exonuclease III. Termination at apurinic sites, like termination at pyrimidine photodimers, involved dissociation of the polymerase from the blocked termini, followed by initiations at available primer templates. When no regular primer templates were available, the polymerase underwent repeated cycles of dissociation and rebinding at the blocked termini and, while bound, carried out multiple polymerization-excision reactions opposite the apurinic sites, leading to turnover of dNTPs into dNMPs. From the in vitro turnover rates, we could predict with striking accuracy the specificity of apurinic site mutagenesis, as determined in vivo in depurinated single-stranded DNA from an M13-lac hybrid phage. This finding is consistent with the view that DNA polymerase III holoenzyme carries out the mutagenic "misinsertion" step during apurinic site mutagenesis in vivo and that the specificity of the process is determined primarily by the polymerase. SOS-induced proteins such as UmuD/C might act as processivity-like factors to stabilize the polymerase-DNA complex, thus increasing the efficiency of the next stage of past-lesion polymerization required to complete the bypass reaction.

Apurinic Acid↗

PubMed1986

Lii-Nao countertransport and Li leak in erythrocytes are differentially affected by membrane enrichment with cholesteryl hemisuccinate.

Enrichment of erythrocytes with cholesteryl hemisuccinate caused a marked reduction in Li leak but did not change kinetic and thermodynamic properties of Lii-Nao countertransport of either normotensive persons or patients with essential hypertension. As cholesteryl hemisuccinate was shown to affect the membrane similarly to cholesterol, it is likely that the unique thermodynamic properties of erythrocyte Lii-Nao countertransport in essential hypertension are not caused by changes in cholesterol.

Cholesterol Esters↗

PubMed1986

Thermodynamic properties of erythrocyte Li efflux may facilitate detection of essential hypertension in pregnant women.

Thermodynamic properties of red cell lithium efflux were examined in pregnant women in relation to hypertension. Twenty-two normotensive women, 15 women with essential hypertension, and 27 with pregnancy-induced hypertension were studied. The rates of Li efflux at 37 degrees C in the three groups of pregnant women were similar and nondiscriminatory. The temperature dependence of the Li efflux, known to be uniquely modified in essential hypertension, allowed the differentiation of most (73%) of the pregnant women with essential hypertension as well. Among the women with pregnancy-induced hypertension, 63% showed a temperature-dependence pattern typical for normotensives, and they may be classified as patients with toxemia of pregnancy. The others (37%) showed a thermodynamic pattern of essential hypertension, but a follow-up study is required to ascertain whether they will indeed develop essential hypertension in the future.

Adult↗

PubMed1984

Li efflux in erythrocytes of pregnant women: comparison of rates and temperature dependence for detection of hypertension.

Two determinants of lithium efflux in erythrocytes were compared, in relation to pregnancy: (a) efflux rates at 37 degrees C; (b) efflux temperature dependence, expressed by the 'break' of Arrhenius plots. Eighteen women were studied both at term and after delivery. While efflux rates were changed markedly, from 0.87 +/- 0.07 to 0.56 +/- 0.05 mmol/ (IRBC h) at term and post-partum, respectively, the characteristic break temperature of each woman remained essentially constant during and after pregnancy. The property of temperature dependence is more suitable than efflux rates for differentiation of hypertension during pregnancy.

Adult↗