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排序方式: 共有882条查询结果,搜索用时 32 毫秒
61.
Canals M Angulo E Casadó V Canela EI Mallol J Viñals F Staines W Tinner B Hillion J Agnati L Fuxe K Ferré S Lluis C Franco R 《Journal of neurochemistry》2005,92(2):337-348
Adenosine A1 receptors (A1Rs) and adenosine A(2A) receptors (A(2A)Rs) are the major mediators of the neuromodulatory actions of adenosine in the brain. In the striatum A1Rs and A(2A)Rs are mainly co-localized in the GABAergic striatopallidal neurons. In this paper we show that agonist-induced stimulation of A1Rs and A(2A)Rs induces neurite outgrowth processes in the human neuroblastoma cell line SH-SY5Y and also in primary cultures of striatal neuronal precursor cells. The kinetics of adenosine-mediated neuritogenesis was faster than that triggered by retinoic acid. The triggering of the expression of TrkB neurotrophin receptor and the increase of cell number in the G1 phase by the activation of adenosine receptors suggest that adenosine may participate in early steps of neuronal differentiation. Furthermore, protein kinase C (PKC) and extracellular regulated kinase-1/2 (ERK-1/2) are involved in the A1R- and A(2A)R-mediated effects. Inhibition of protein kinase A (PKA) activity results in a total inhibition of neurite outgrowth induced by A(2A)R agonists but not by A1R agonists. PKA activation is therefore necessary for A(2A)R-mediated neuritogenesis. Co-stimulation does not lead to synergistic effects thus indicating that the neuritogenic effects of adenosine are mediated by either A1 or A(2A) receptors depending upon the concentration of the nucleoside. These results are relevant to understand the mechanisms by which adenosine receptors modulate neuronal differentiation and open new perspectives for considering the use of adenosine agonists as therapeutic agents in diseases requiring neuronal repair. 相似文献
62.
63.
The synergistic interaction between xanthan and glucomannan in solution and in the gel phase has been studied by circular dichroism spectroscopy and differential scanning calorimetry. The study in solution of the polysaccharidic mixture indicates a preferred stoichiometry of the interaction corresponding to a weight fraction of xanthan around 0.55. This finding is in reasonable agreement with the differential scanning calorimetry measurements carried out on the gel phase. Models from conformational analysis based on these results were formulated in terms of 1:1 and 2:1 Konjac glucomannan/xanthan molecular assemblies. The experimental and calculation results clearly indicate the involvement of the side chains of xanthan and suggest that the ordered portions of the macromolecular complex in solution act in the gel phase as junction zones. 相似文献
64.
Hammond EM Denko NC Dorie MJ Abraham RT Giaccia AJ 《Molecular and cellular biology》2002,22(6):1834-1843
65.
Heba Diab Masashi Ohira Mali Liu Ester Cobb Patricia M. Kane 《The Journal of biological chemistry》2009,284(20):13316-13325
Disassembly of the yeast V-ATPase into cytosolic V1 and membrane
V0 sectors inactivates MgATPase activity of the
V1-ATPase. This inactivation requires the V1 H subunit
(Parra, K. J., Keenan, K. L., and Kane, P. M. (2000) J. Biol. Chem.
275, 21761–21767), but its mechanism is not fully understood. The H
subunit has two domains. Interactions of each domain with V1 and
V0 subunits were identified by two-hybrid assay. The B subunit of
the V1 catalytic headgroup interacted with the H subunit N-terminal
domain (H-NT), and the C-terminal domain (H-CT) interacted with V1
subunits B, E (peripheral stalk), and D (central stalk), and the cytosolic
N-terminal domain of V0 subunit Vph1p. V1-ATPase
complexes from yeast expressing H-NT are partially inhibited, exhibiting 26%
the MgATPase activity of complexes with no H subunit. The H-CT domain does not
copurify with V1 when expressed in yeast, but the bacterially
expressed and purified H-CT domain inhibits MgATPase activity in V1
lacking H almost as well as the full-length H subunit. Binding of full-length
H subunit to V1 was more stable than binding of either H-NT or
H-CT, suggesting that both domains contribute to binding and inhibition.
Intact H and H-CT can bind to the expressed N-terminal domain of Vph1p, but
this fragment of Vph1p does not bind to V1 complexes containing
subunit H. We propose that upon disassembly, the H subunit undergoes a
conformational change that inhibits V1-ATPase activity and
precludes V0 interactions.V-ATPases are ubiquitous proton pumps responsible for compartment
acidification in all eukaryotic cells
(1,
2). These pumps couple
hydrolysis of cytosolic ATP to proton transport into the lysosome/vacuole,
endosomes, Golgi apparatus, clathrin-coated vesicles, and synaptic vesicles.
Through their role in organelle acidification, V-ATPases are linked to
cellular functions as diverse as protein sorting and targeting, zymogen
activation, cytosolic pH homeostasis, and resistance to multiple types of
stress (3). They are also
recruited to the plasma membrane of certain cells, where they catalyze proton
export (4,
5).V-ATPases are evolutionarily related to ATP synthases of bacteria and
mitochondria and consist of two multisubunit complexes, V1 and
V0, which contain the sites for ATP hydrolysis and proton
transport, respectively. Like the ATP synthase (F-ATPase), V-ATPases utilize a
rotational catalytic mechanism. ATP binding and hydrolysis in the three
catalytic subunits of the V1 sector generate sequential
conformational changes that drive rotation of a central stalk
(6–8).
The central stalk subunits are connected to a ring of proteolipid subunits in
the V0 sector that bind protons to be transported. The actual
transport is believed to occur at the interface of the proteolipids and
V0 subunit a. Rotational catalysis will be productive in proton
transport only if V0 subunit a is held stationary, whereas the
proteolipid ring rotates (8).
This “stator function” resides in a single peripheral stalk in
F-ATPases (9,
10), but is distributed among
up to three peripheral stalks in V-ATPases
(11–13).
The peripheral stator stalks link V0 subunit a to the catalytic
headgroup and ensures that there is rotation of the central stalk complex
relative to the V0 a subunit and catalytic headgroup.Eukaryotic V-ATPases are highly conserved in both their overall structure
and the sequences of individual subunits. Although homologs of most subunits
of eukaryotic V-ATPases are present in archaebacterial V-ATPases (also known
as A-ATPases), the C and H subunits are unique to eukaryotes. Both subunits
have been localized at the interface of the V1 and V0
sectors, suggesting that they are positioned to play a critical role in
structural and functional interaction between the two sectors
(14–16).
The yeast C and H subunits are the only eukaryotic V-ATPase subunits for which
x-ray crystal structures are available
(17,
18). The structure of the C
subunit revealed an elongated “dumbbell-shaped” molecule, with
foot, head, and neck domains
(18). The structure of the H
subunit indicated two domains. The N-terminal 348 amino acids fold into a
series of HEAT repeats and are connected by a 4-amino acid linker to a
C-terminal domain containing amino acids 352–478
(17). These two domains have
partially separable functions in the context of the assembled V-ATPase
(19). Complexes containing
only the N-terminal domain of the H subunit
(H-NT)2 supported some
ATP hydrolysis but little or no proton pumping in isolated vacuolar vesicles
(19,
20). The C-terminal domain
(H-CT) assembled with the rest of the V-ATPase in the absence of intact
subunit H, but supported neither ATPase nor proton pumping activity
(19). However, co-expression
of the H-NT and H-CT domains results in assembly of both sectors with the
V-ATPase and allows increased ATP-driven proton pumping in isolated vacuolar
vesicles. These results suggest that the H-NT and H-CT domains play distinct
and complementary roles even when the two domains are not covalently
attached.In addition to their role as dedicated proton pumps, eukaryotic V-ATPases
are also distinguished from F-ATPases and archaeal V-ATPases in their
regulation. Eukaryotic V-ATPases are regulated in part by reversible
disassembly of the V1 complex from the V0 complex
(1,
21,
22). In yeast, disassembly of
previously assembled complexes occurs in response to glucose deprivation, and
reassembly is rapidly induced by glucose readdition to glucose-deprived cells.
Disassembly down-regulates pump activity, and both the disassembled sectors
are inactivated. Inhibition of ATP hydrolysis in free V1 sectors is
particularly critical, because release of an active ATPase into the cytosol
could deplete cytosolic ATP stores. This inhibition is dependent in part on
the H subunit. V1 complexes isolated from vma13Δ
mutants, which lack the H subunit gene (V1(-H) complexes) have
MgATPase activity. Consistent with a physiological role for H subunit
inhibition of V1, heterozygous diploids containing elevated levels
of free V1 complexes without subunit H have severe growth defects
(23). V1 complexes
containing subunit H have no MgATPase activity, but retain some CaATPase
activity, suggesting a role for nucleotides in inhibition
(24,
25). Consistent with such a
role, both the CaATPase activity of native V1 and the MgATPase
activity of V1(-H) complexes are lost within a few minutes of
nucleotide addition (24).A number of points of interaction between the H subunit and the
V1 and V0 complexes have been identified through
two-hybrid assays, binding of expressed proteins, and cross-linking
experiments. These experiments have indicated that the H subunit binds to
V1 subunits E and G of the V-ATPase peripheral stalks
(26,
27), the catalytic subunit
(V1 subunit A)
(28), regulatory V1
subunit B (15), and the
N-terminal domain of subunit a
(28). Recently, Jeffries and
Forgac (29) have found that
cysteines introduced into the C-terminal domain of subunit H can be
cross-linked to subunit F in isolated V1 sectors via a 10-Å
cross-linking reagent.In this work, we examine both the subunit-subunit interactions and
functional roles of the H-NT and H-CT domains in inhibition of
V1-ATPase activity. When expressed in yeast cells lacking subunit
H, H-NT can be isolated with cytosolic V1 complexes, but H-CT
cannot. We find that both of these domains contribute to inhibition of ATPase
activity, but that stable binding to V1 and full inhibition of
activity requires both domains. We also find that the H-CT can bind to the
cytosolic N-terminal domain of V0 subunit Vph1p (Vph1-NT) in
isolation, but does not support tight binding of Vph1-NT to isolated
V1 complexes. 相似文献
66.
Itzhak Zander Ester Shmidov Shira Roth Yossi Ben-David Irit Shoval Sivan Shoshani Amos Danielli Ehud Banin 《Environmental microbiology》2020,22(12):5048-5057
Toxin–antitoxin (TA) systems are small genetic modules usually consisting of two elements—a toxin and an antitoxin. The abundance of TA systems among various bacterial strains may indicate an important evolutionary role. Pseudomonas aeruginosa, which can be found in a variety of niches in nature, is an opportunistic pathogen for various hosts. While P. aeruginosa strains are very versatile and diverse, only a few TA systems were characterized in this species. Here, we describe a newly characterized TA system in P. aeruginosa that is encoded within the filamentous Pf4 prophage. This system, named PfiT/PfiA, is a homologue of the ParE/YefM TA system. It is a type II TA system, in which the antitoxin is a protein that binds the toxic protein and eliminates the toxic effect. PfiT/PfiA carries several typical type II characteristics. Specifically, it constitutes two small genes expressed in a single operon, PfiT inhibits growth and PfiA eliminates this effect, PfiA binds PfiT, and PfiT expression results in elongated cells. Finally, we assigned a novel function to this TA system, where an imbalance between PfiT and PfiA, favouring the toxin, resulted in cell elongation and an increase in virion production. 相似文献
67.
68.
Taíse F. Pedroso Cláudia S. Oliveira Mariana M. Fonseca Vitor A. Oliveira Maria Ester Pereira 《Biological trace element research》2017,180(2):275-284
This study investigated the toxicity of rats exposed to lead acetate (AcPb) during the second phase of brain development (8–12 days postnatal) in hematological and cerebral parameters. Moreover, the preventive effect of zinc chloride (ZnCl2) and N-acetylcysteine (NAC) was investigated. Pups were injected subcutaneously with saline (0.9% NaCl solution), ZnCl2 (27 mg/kg/day), NAC (5 mg/kg/day) or ZnCl2 plus NAC for 5 days (3rd–7th postnatal days), and with saline (0.9% NaCl solution) or AcPb (7 mg/kg/day) in the five subsequent days (8th–12th postnatal days). Animals were sacrificed 21 days after the last AcPb exposure. Pups exposed to AcPb presented inhibition of blood porphobilinogen-synthase (PBG-synthase) activity without changes in hemoglobin content. ZnCl2 pre-exposure partially prevented PBG-synthase inhibition. Regarding neurotoxicity biomarkers, animals exposed to AcPb presented a decrease in cerebrum acetylcholinesterase (AChE) activity and an increase in Pb accumulation in blood and cerebrum. These changes were prevented by pre-treatment with ZnCl2, NAC, and ZnCl2 plus NAC. AcPb exposure caused no alteration in behavioral tasks. In short, results show that AcPb inhibited the activity of two important enzymatic biomarkers up to 21 days after the end of the exposure. Moreover, ZnCl2 and NAC prevented the alterations induced by AcPb. 相似文献
69.
Although climate warming is affecting most marine ecosystems, the Mediterranean is showing earlier impacts. Foundation seagrasses are already experiencing a well‐documented regression in the Mediterranean which could be aggravated by climate change. Here, we forecast distributions of two seagrasses and contrast predicted loss with discrete regions identified on the basis of extant genetic diversity. Under the worst‐case scenario, Posidonia oceanica might lose 75% of suitable habitat by 2050 and is at risk of functional extinction by 2100, whereas Cymodocea nodosa would lose only 46.5% in that scenario as losses are compensated with gained and stable areas in the Atlantic. Besides, we predict that erosion of present genetic diversity and vicariant processes can happen, as all Mediterranean genetic regions could decrease considerably in extension in future warming scenarios. The functional extinction of Posidonia oceanica would have important ecological impacts and may also lead to the release of the massive carbon stocks these ecosystems stored over millennia. 相似文献
70.
Passive immunization reduces murine cytomegalovirus-induced brain pathology in newborn mice 下载免费PDF全文
Cekinović D Golemac M Pugel EP Tomac J Cicin-Sain L Slavuljica I Bradford R Misch S Winkler TH Mach M Britt WJ Jonjić S 《Journal of virology》2008,82(24):12172-12180
Human cytomegalovirus (HCMV) is the most frequent cause of congenital viral infections in humans and frequently leads to long-term central nervous system (CNS) abnormalities that include learning disabilities, microcephaly, and hearing loss. The pathogenesis of the CNS infection has not been fully elucidated and may arise as a result of direct damage of CMV-infected neurons or indirectly secondary to inflammatory response to infection. We used a recently established model of mouse CMV (MCMV) infection in newborn mice to analyze the contribution of humoral immunity to virus clearance from the brain. In brains of MCMV-infected newborn mice treated with immune serum, the titer of infectious virus was reduced below detection limit, whereas in the brains of mice receiving control (nonimmune) serum significant amounts of virus were recovered. Moreover, histopathological and immunohistological analyses revealed significantly less CNS inflammation in mice treated with immune serum. Treatment with MCMV-specific monoclonal antibodies also resulted in the reduction of virus titer in the brain. Recipients of control serum or irrelevant antibodies had more viral foci, marked mononuclear cell infiltrates, and prominent glial nodules in their brains than mice treated with immune serum or MCMV-specific antibodies. In conclusion, our data indicate that virus-specific antibodies have a protective role in the development of CNS pathology in MCMV-infected newborn mice, suggesting that antiviral antibodies may be an important component of protective immunological responses during CMV infection of the developing CNS. 相似文献