共查询到20条相似文献,搜索用时 15 毫秒
1.
2.
3.
The relationships between anxiety/stress, possible endogenous ligands for benzodiazepine receptors and the behavioral modification by drugs are discussed in this short review, including the specific characteristics of elements involved in those interactions, e.g. ones concerning the aversiveness of the stressful situation and the nature of the organism under investigation. These are important factors when considering aversive tasks, insofar as they may involve stressful conditions which differ in intensity and in the degree of control afforded the subject. These characteristics may well lead to differing functional effects on GABA-gated chloride channels or, in other words, to an incongruous balance between endogenous benzodiazepine receptor agonist and inverse agonist activity. This is not surprising, as it is well known that different forms of stressors often actually produce divergent behavioral, physiological and biochemical effects. This review also illustrates the necessity of taking into account the variable effects of stressors and/or drugs on animals differing in reactivity or emotionality, even in the case of 'non-selected' stocks. The implication is made that, by genetic and/or environmental manipulation of the emotional state of the animals used, it will be possible to obtain more clearly definable results in neuropharmacological and psychopharmacological studies. 相似文献
4.
L.A. Pile F.W.-H. Lee D.A. Wassarman 《Cellular and molecular life sciences : CMLS》2001,58(11):1715-1718
We examined the consequences of the deacetylase inhibitor trichostatin A (TSA) on the development of Drosophila melanogaster. When fed to flies, TSA caused lethality and delayed development at concentrations as low as 5 μM, had stronger effects on
males than females, and acted synergistically with mutations in the gene encoding the RPD3 deacetylase to cause notched wings,
but did not appear to affect a SINA signaling pathway that is normally repressed by the SIN3 corepressor. These findings suggest
that deacetylated histones play an important role in normal developmental progression and establish parameters for genetic
screens to dissect the role of deacetylases in this process.
Received 14 June 2001; received after revision 31 July 2001; accepted 21 August 2001 相似文献
5.
Endogenous opioids have been studied extensively since their discovery, in the hope of finding a perfect analgesic, devoid
of the secondary effects of alkaloid opioids. However, the design of selective opioid agonists has proved very difficult.
First, structural studies of peptides in general are hampered by their intrinsic flexibility. Second, the relationship between
constitution and the so-called 'bioactive conformation' is far from obvious. Ideally, a direct structural study of the complex
between a peptide and its receptor should answer both questions, but such a study is not possible, because opioid receptors
are large membrane proteins, difficult to study by standard structural techniques. Thus, conformational studies of opioid
peptides are still important for drug design and also for indirect receptor mapping. This review deals with conformational
studies of natural opioid peptides in several solvents that mimic in part the different environments in which the peptides
exert their action. None of the structural investigations yields a convincing bioactive conformation, but the global conformation
of longer peptides in biomimetic environments can shed light on the interaction with receptors.
Received 15 April 2001; received after revision 10 May 2001; accepted 11 May 2001 相似文献
6.
A. Fernández-Teruel R. M. Escorihuela A. Tobeña P. Driscoll 《Cellular and molecular life sciences : CMLS》1991,47(10):1051-1056
The relationships between anxiety/stress, possible endogenous ligands for benzodiazepine receptors and the behavioral modification by drugs are discussed in this short review, including the specific characteristics of elements involved in those interactions, e.g. ones concerning the aversiveness of the stressful situation and the nature of the organism under investigation. These are important factors when considering aversive tasks, insofar as they may involve stressful conditions which differ in intensity and in the degree of control afforded the subject. These characteristics may well lead to differing functional effects on GABA-gated chloride channels or, in other words, to an incongruous balance between endogenous benzodiazepine receptor agonist and inverse agonist activity. This is not surprising, as it is well known that different forms of stressors often actually produce divergent behavioral, physiological and biochemical effects. This review also illustrates the necessity of taking into account the variable effects of stressors and/or drugs on animals differing in reactivity or emotionality, even in the case of non-selected stocks. The implication is made that, by genetic and/or environmental manipulation of the emotional state of the animals used, it will be possible to obtain more clearly definable results in neuropharmacological and psychopharmacological studies. 相似文献
7.
The prolyl oligopeptidase family 总被引:6,自引:0,他引:6
Polgár L 《Cellular and molecular life sciences : CMLS》2002,59(2):349-362
A group of serine peptidases, the prolyl oligopeptidase family, cannot hydrolyze peptides containing more than about 30 residues.
This group is unrelated to the classical trypsin and subtilisin families, and includes dipeptidyl peptidase IV, acylaminoacyl
peptidase and oligopeptidase B, in addition to the prototype prolyl oligopeptidase. The recent crystal structure determination
of prolyl oligopeptidase (80 kDa) has shown that the enzyme contains a peptidase domain with an α/β hydrolase fold, and its catalytic triad is covered by the central tunnel of an unusual seven-bladed β-propeller. This domain operates as a gating filter, excluding large, structured peptides from the active site. The binding
mode of substrates and the catalytic mechanism differ from that of the classical serine peptidases in several features. The
members of the family are important targets of drug design. Prolyl oligopeptidase is involved in amnesia, depression and blood
pressure control, dipeptidyl peptidase IV in type 2 diabetes and oligopeptidase B in trypanosomiasis.
Received 8 August 2001; received after revision 19 September 2001; accepted 21 September 2001 相似文献
8.
Aging appears to be an irreversible process. Here we report that nicotinamide (NAA) can induce rapid and reversible reversion
of aging phenotypes in human diploid fibroblasts in terms of cell morphology and senescence-associated β-galactosidase activity.
Although NAA seems to enhance the replicative potential of the cells, it has little effect on their growth rate and life span,
suggesting that NAA action is rather separated from the cellular replicative system. The effects are unique to NAA: none of
the NAA-related compounds examined (an NAD precursor/niacin, NAD analogs, and poly(ADP-ribose) polymerase inhibitors) exerted
similar effects. Thus, NAD-related metabolism and poly(ADP-ribosyl)ation are unlikely related to the NAA action. On the other
hand, histone acetyltransferase (HAT) activity was elevated in NAA-exposed cells, while in aged cells, HAT activity and histone
H4 acetylation were lowered. Taken together, the results suggest that NAA may cause rejuvenation by restoring, at least in
part, altered gene expression in aged cells through its activation of HAT.
Received 27 August 2001; received after revision 15 October 2001; accepted 15 October 2001 相似文献
9.
Evidence of undiscovered cell regulatory mechanisms: phosphoproteins and protein kinases in mitochondria 总被引:3,自引:0,他引:3
Thomson M 《Cellular and molecular life sciences : CMLS》2002,59(2):213-219
The finding that mitochondria contain substrates for protein kinases lead to the discovery that protein kinases are located
in the mitochondria of certain tissues and species. These include pyruvate dyhydrogenase kinase, branched-chain α-ketoacid dehydrogenase kinase, protein kinase A, protein kinase Cδ, stress-activated kinase and A-Raf as well as unidentified kinases. Recent evidence suggests that mitochondrial protein kinases
may be involved in physiological processes such as apoptosis and steroidogenesis. Additionally, the novel finding of low-molecular-weight
GTP-binding proteins in mitochondria suggests the possibility that these may interact with mitochondrial protein kinases to
regulate the activity of mitochondrial effector proteins. The fact that there are components of cellular regulatory systems
in mitochondria indicates the exciting possibility of undiscovered systems regulating mitochondrial physiology.
Received 19 June 2001; received after revision 7 August 2001; accepted 8 August 2001 相似文献
10.
Malaria results in up to 2.5 million deaths annually, with young children and pregnant women at greatest risk. The great
majority of severe disease is caused by Plasmodium falciparum. A characteristic feature of infection with P. falciparum is the accumulation or sequestration of parasite-infected red blood cells (RBCs) in various organs, such as the brain, lung
and placenta, and together with other factors is important in the pathogenesis of severe forms of malaria. Sequestration results
from adhesive interactions between parasite-derived proteins expressed on the surface of infected RBCs and a number of host
molecules on the surface of endothelial cells, placental cells and uninfected RBCs. Some receptors for parasite adhesion have
been implicated in particular malaria syndromes, such as intercellular adhesion molecule 1 in cerebral malaria and chondroitin
sulfate A and hyaluronic acid in placental infection. The principal parasite ligand and antigen on the RBC surface, P. falciparum erythrocyte membrane protein 1 encoded by a multigene family termed var, is clonally variant, enabling evasion of specific immune responses. An understanding of these host-parasite interactions
in the context of clinical disease and immunity may reveal potential targets to prevent or treat severe forms of malaria.
Received 25 June 2001; received after revision 22 August 2001; accepted 24 August 2001 相似文献
11.
Tsatsanis C Dermitzaki E Venihaki M Chatzaki E Minas V Gravanis A Margioris AN 《Cellular and molecular life sciences : CMLS》2007,64(13):1638-1655
Corticotropin-releasing factor (CRF), also termed corticotropin-releasing hormone (CRH) or corticoliberin, is the major regulator
of the adaptive response to internal or external stresses. An essential component of the adaptation mechanism is the adrenal
gland. CRF regulates adrenal function indirectly through the central nervous system (CNS) via the hypothalamic-pituitary-adrenal
(HPA) axis and via the autonomic nervous system by way of locus coeruleus (LC) in the brain stem. Accumulating evidence suggests
that CRF and its related peptides also affect the adrenals directly, i.e. not through the CNS but from within the adrenal gland where they form paracrine regulatory loops. Indeed, CRF and its related
peptides, the urocortins (UCNs: UCN1, UCN2 and UCN3), their receptors CRF type 1 (CRF1) and 2 (CRF2) as well as the endogenous pseudo-receptor CRF-binding protein (CRF-BP) are all expressed in adrenal cortical, medullary
chromaffin and resident immune cells. The intra-adrenal CRF-based regulatory system is complex and depends on the balance
between the local concentration of CRF ligands and the availability of their receptors.
Received 19 December 2006; received after revision 20 February 2007; accepted 26 March 2007 相似文献
12.
Immunological evidence suggests that plants, like vertebrates, contain natriuretic peptides (NPs) and that rat atrial NP
(rANP) binds specifically to plant membranes and promotes concentration and conformation-dependent stomatal opening. Stomatal
opening and specific increases in cGMP levels were also observed in response to immunoreactive plant NP (irPNP). Here we report
that both 1 μM rANP and irPNP (100 ng total protein/100 μL) significantly increase radial water movements out of the xylem
of shoots of Tradescantia multiflora. Enhanced radial water movements are also observed in response to the cell permeant cGMP analogue 8-Br-cGMP (100 nM). The
water channel inhibitor mercuric chloride (HgCl2) significantly inhibits radial water movements at concentrations of 50 μM, while the presence of 10 μM 2-hydroxyethylmercaptoethanol
(ME) prevents the inhibitory effect of the mercurial. The guanylate cyclase inhibitor LY 83583 at a concentration of 20 μM
and sodium azide (NaN3) at concentrations of ≥ 1 μM both also reduce radial water movements. We therefore conclude that the regulation of radial
water movement out of the xylem involves modulation of cGMP levels, water channels and respiration-dependent processes. In
addition, we propose that NPs have a critical role to play in radial water movements out of the xylem and speculate that as
in vertebrates, NP effects might, at least in part, be mediated via the regulation of guanylate cyclases and water channels.
Received 15 June 1998; received after revision 7 August 1998; accepted 26 August 1998 相似文献
13.
Axonal transport of neurofilaments in normal and disease states 总被引:5,自引:0,他引:5
Miller CC Ackerley S Brownlees J Grierson AJ Jacobsen NJ Thornhill P 《Cellular and molecular life sciences : CMLS》2002,59(2):323-330
Neurofilaments are among the most abundant organelles in neurones. They are synthesised in cell bodies and then transported
into and through axons by a process termed 'slow axonal transport' at a rate that is distinct from that driven by conventional
fast motors. Several recent studies have now demonstrated that this slow rate of transport is actually the consequence of
conventional fast rates of movement that are interrupted by extended pausing. At any one time, most neurofilaments are thus
stationary. Accumulations of neurofilaments are a pathological feature of several human neurodegenerative diseases suggesting
that neurofilament transport is disrupted in disease states. Here, we review recent advances in our understanding of neurofilament
transport in both normal and disease states. Increasing evidence suggests that phosphorylation of neurofilaments is a mechanism
for regulating their transport properties, possibly by promoting their detachment from the motor(s). In some neurodegenerative
diseases, signal transduction mechanisms involving neurofilament kinases and phosphatases may be perturbed leading to disruption
of transport.
Received 11 July 2001; received after revision 30 August 2001; accepted 31 August 2001 相似文献
14.
Lisowska E 《Cellular and molecular life sciences : CMLS》2002,59(3):445-455
Glycosylation of proteins is a common event and contributes to protein antigenic properties. Most data have been obtained
from model studies on glycoprotens with well-defined structure or synthetic glycopeptides and their respective monoclonal
antibodies. Antibodies raised against glycoprotein antigens may be specific for their carbohydrate units which are recognized
irrespective of the protein carrier (carbohydrate epitopes), or in the context of the adjacent amino acid residues (glycopeptidic
epitopes). Conformation or proper exposure of peptidic epitopes of glycoproteins is also frequently modulated by glycosylation
due to intramolecular carbohydrate-protein interactions. The effects of glycosylation are broad: glycosylation may 'inactivate'
the peptidic epitope or may be required for its reactivity with the antibody, depending on the structure of the antigenic
site and antibody fine specificity. Evidence is increasing that similar effects of glycosylation pertain to T cell-dependent
cellular immune responses. Glycosylated peptides can be bound and presented by MHC class I or II molecules and elicit glycopeptide-specific
T cell clones.
Received 5 July 2001; received after revision 9 October 2001; accepted 11 October 2001 相似文献
15.
Significance and molecular targets of protein kinase A during cAMP-mediated protection of cold stored liver grafts 总被引:6,自引:0,他引:6
The use of marginal donor livers is followed by a higher frequency of primary dys- or nonfunction after transplantation.
The present study was designed to test the hypothesis that stimulation of the cAMP second-messenger signal pathway might protect
the liver from ischemic injury, laying emphasis on the role of protein kinase A-mediated signal transduction.?Rat livers were
harvested after 45 min of cardiac arrest and preserved in HTK solution for 24 h. Hepatic integrity was assessed thereafter
using a blood-free reperfusion model.?Supplementation of the preservation solution with dibutyryl-cAMP (db-cAMP) promoted
phosphorylation of BAD at Ser 112 and concomitantly mitigated mitochondrial release of cytochrome c into the cytosol. Apoptotic
cell transformation was evident in reperfused livers by positive TUNEL-staining of sinusoidal lining cells and the detection
of cleaved poly(ADP-ribose) polymerase (PARP) in tissue homogenates by western analysis. Treatment with db-cAMP was effective
in minimizing both TUNEL staining and PARP cleavage and significantly reduced postischemic enzyme leakage of alanine aminotransferase
to one half, while hepatic bile production was enhanced by approximately 60% when compared to untreated livers. This functional
improvement was accompanied by a net amelioration of portal vascular conductivity. Inhibition of A kinase-anchoring protein
with HT31 completely reversed any of the observed effects obtained by db-cAMP.?We conclude that enhancement of cellular cAMP
signal maintains hepatic integrity during and after ischemic preservation which may be attributed to protein kinase A dependent
phosphorylation of BAD in line with subsequent inhibition of mitochondria-initiated apoptosis of sinusoidal lining cells.
Received 12 July 2001; received after revision 14 August 2001; accepted 14 August 2001 相似文献
16.
17.
Protein farnesylation in mammalian cells: effects of farnesyltransferase inhibitors on cancer cells 总被引:3,自引:0,他引:3
F. Tamanoi C.-L. Gau C. Jiang H. Edamatsu J. Kato-Stankiewicz 《Cellular and molecular life sciences : CMLS》2001,58(11):1636-1649
Protein farnesylation, catalyzed by protein farnesyltransferase, plays important roles in the membrane association and protein-protein
interaction of a number of eukaryotic proteins. Recent development of farnesyltransferase inhibitors (FTIs) has led to further
insight into the biological significance of farnesylation in cancer cells. A number of reports point to the dramatic effects
FTIs exert on cancer cells. In addition to inhibiting anchorage-independent growth, FTIs cause changes in the cell cycle either
at the G1/S or at the G2/M phase. Furthermore, induction of apoptosis by FTIs has been reported. FTIs also affects the actin
cytoskeleton and cell morphology. This review summarizes these reports and discusses implications for farnesylated proteins
responsible for these FTI effects.
Received 17 April 2001; received after revision 28 May 2001; accepted 28 May 2001 相似文献
18.
Molina H 《Cellular and molecular life sciences : CMLS》2002,59(2):220-229
Complement has an important role in inflammation and in the normal function of the immune system. Activated complement fragments
have the capacity to bind and damage self-tissues. Cells from vertebrates express on their surface regulators of complement
activation that protect them from the deleterious effects of cell-bound complement fragments. Abnormalities in these regulators
of complement activation may participate in the pathogenesis of autoimmune diseases and inflammatory disorders. Murine Crry
is one of these regulators that inhibits the activation of the third component of complement and protects self-tissues from
complement-mediated damage. Experimental work on Crry has increased our understanding of the immunobiology of complement regulation
and the potential role of complement and complement inhibitors in the development and treatment of human diseases.
Received 13 June 2001; received after revision 12 July 2001; accepted 9 August 2001 相似文献
19.
Trefoil factors 总被引:6,自引:0,他引:6
Hoffmann W 《Cellular and molecular life sciences : CMLS》2005,62(24):2932-2938
Rapid repair of mucous epithelia is essential for preventing inflammation which is a critical component of cancer progression. 'Restitution' is an early repair process which can begin within minutes and is achieved via the migration of neighbouring cells into the wounded area. Mucosal restitution is a multistep process which requires continuous blood flow and includes at least (i) the reduction of cell-cell contacts and a shift in the cell shape towards a migratory phenotype (characteristics of the epithelial-mesenchymal transition), (ii) migration of cells, (iii) repolarization and formation of tight junctions (morphological restitution) and (iv) restoration of barrier function (transmucosal epithelial resistance, functional restitution). Secretory TFF (trefoil factor family) peptides TFF1, TFF2 and TFF3 are well known for their potent protective and healing effects after mucosal damage (function as 'luminal surveillance peptides'). Here, the contributions of the TFFs during the different steps of mucosal restitution are discussed, i. e. the modulation of cell-cell contacts, their motogenic activity and synergy with epidermal growth factor, their anti-apoptotic and pro-angiogenic effects. Special emphasis has been given to discussion of the various signal transduction networks triggered by TFFs. It is becoming increasingly clear that these pathways differ depending on the respective TFF. 相似文献
20.
Activation of immediate early genes and memory formation 总被引:14,自引:0,他引:14