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1.
In this study we evaluated the effect of quercetin on D-galactose-induced aged mice using the Morris water maze (MWM) test. Based on the free radical theory of aging,experiments were performed to study the possible biochemical mechanisms of glutathione (GSH) level and hydroxyl radical (OH-) in the hippocampus and cerebral cortex and the brain tissue enzyme activity of the mice. The results indicated that quercetin can enhance the exploratory behavior,spatial learning and memory of the mice. The effects relate with enhancing the brain functions and inhibiting oxidative stress by quercetin,and relate with increasing the GSH level and decreasing the OH-content. These findings suggest that quercetin can work as a possible natural anti-aging pharmaceutical product. 相似文献
2.
3.
Repair effects of rutin and quercetin on purine deoxynucleotide radical cations were studied using pulse radiolysis technique. On electron pulse irradiation of N2 saturated deoxynucleotide aqueous solution containing 20 mmol/L K2S2O8, 200 mmol/Lt-BuOH and rutin or quercetin, the transient absorption spectra of the deoxynucleotide radical cations decayed quickly. At the same time, the spectra of flavonoid phenoxyl radicals formed within several dozen microseconds. The results indicated that deoxynucleotide radical cations can be repaired by flavonoids. The rate constants of the repair reactions were 3.8 ×108-4.4 ×108 mol−1 · L · s−1 and 1.3×108-1.8×108 mol−1 · L · s−1 for dAMP and dGMP radical cations, respectively. 相似文献
4.
Repair effects of rutin and quercetin on purine deoxynucleotide radical cations were studied using pulse radiolysis technique. On electron pulse irradiation of N2 saturated deoxynucleotide aqueous solution containing 20 mmol/L K2S2O8, 200 mmol/L f-BuOH and rutin or quercetin, the transient absorption spectra of the deoxynucleotide radical cations decayed quickly. At the same time, the spectra of flavonoid phenoxyl radicals formed within several dozen microseconds. The results indicated that deoxynucleotide radical cations can be repaired by flavonoids. The rate constants of the repair reactions were 3.8 × 108-4.4×108 mol-1 · L · s-1 and 1.3×108-1.8×108 mol-1 · L · s-1 for dAMP and dGMP radical cations, respectively. 相似文献
5.
The possible ameliorative effects of quercetin on soybean [Glycine max (L.) Merr.] leaves exposed to UV-B radiation were conducted in greenhouse. The symmetrical leaves supplied with quercetin
solution (0.2%, 1%) were exposed to UV-B radiation (0, 3.5, 6.5 kJ m−2 d−1). 0.2% quercetin ameliorated leaf photosynthesis, improved leaf water content (LWC), and decreased lipid oxidation. The unfavorable
effect on photosynthetic parameter was displayed in 1% quercetin treatment. The effect of quercetin on phenylalanine ammonia
lyase (PAL) activity varied with the quercetin concentration, UV-B radiation intensity and leaf development. In the later
development polyphenol oxidase (PPO) activity was increased significantly by quercetin treatments. We suggested that quercetin
with suitable concentration could serve as UV-B protective agent partly due to its antioxidant capacity. 相似文献
6.
We investigate the electrophysiological salt stress response of the salt-sensitive charophyte Chara australis as a function of time in saline artificial pond water (saline APW) containing 50 mM NaCl and 0.1 mM CaCl2. The effects are due to an increase in Na+ concentration rather than an increase in Cl− concentration or medium osmolarity. A previous paper (Shepherd et al. Plant Cell Environ 31:1575–1591, 2008) described the
rise in the background conductance and inhibition of proton pumping in saline APW in the first 60 min. Here we investigate
the shift of membrane potential difference (PD) to levels above −100 mV and the change of shape of the current–voltage (I/V)
profiles to upwardly concave. Arguing from thermodynamics, the I/V characteristics can be modeled by channels that conduct
H+ or OH−. OH− was chosen, as H+ required an unrealistic increase in the number/permeability of the channels at higher pH levels. Prolonged exposure to saline
APW stimulated opening of more OH− channels. Recovery was still possible even at a PD near −50 mV, with partial return of proton pumping and a decrease in OH− current following APW wash. Upon change of pH from 7 to 9, the response was consistent with previously observed I/V characteristics
of OH− channels. For a pH change to 6, the response was transient before channel closure but could still be modeled. The consequences
of opening of H+ or OH− channels while the cell is under salt stress are discussed. 相似文献
7.
Release of iron from ferritin requires reduction of ferric to ferrous iron. The iron can participate in the diabetogenic action
of alloxan. We investigated the ability of ascorbate to catalyze the release of iron from ferritin in the presence of alloxan.
Incubation of ferritin with ascorbate alone elicited iron release (33 nmol/10 min) and the generation of ascorbate free radical,
suggesting a direct role for ascorbate in iron reduction. Iron release by ascorbate significantly increased in the presence
of alloxan, but alloxan alone was unable to release measurable amounts of iron from ferritin. Superoxide dismutase significantly
inhibited ascorbate-mediated iron release in the presence of alloxan, whereas catalase did not. The amount of alloxan radical
(A·−) generated in reaction systems containing both ascorbate and alloxan decreased significantly upon addition of ferritin, suggesting
that A·− is directly involved in iron reduction. Although release of iron from ferritin and generation of A·− were also observed in reactions containing GSH and alloxan, the amount of iron released in these reactions was not totally
dependent on the amount of A·− present, suggesting that other reductants in addition to A·− (such as dialuric acid) may be involved in iron release mediated by GSH and alloxan. These results suggest that A·− is the main reductant involved in ascorbate-mediated iron release from ferritin in the presence of alloxan and that both
dialuric acid and A·− contribute to GSH/alloxan-mediated iron release. 相似文献
8.
A topic emerging roughly 30 years ago and engendering an incompletely resolved controversy is reviewed in this article: the
relatively high permeability and pH independence associated with H+/OH− passive movements across lipid membranes. We summarize the expected characteristics of simple H+/OH− diffusion and those of a reaction between H+ and OH− being attracted from opposite surfaces and condensing in an interfacial zone of the membrane. An interfacial H+/OH− reaction mechanism gives the experimentally observed behavior of an H+/OH− flux that is independent of the pH measurement range. This mechanism assumes that H+ and OH− within the interfacial zone become electrostatically aligned on opposite sides of the hydrophobic membrane core. Electrostatic
attraction and charge delocalization among a small cluster of water molecules surrounding the ions reduce the Born energy
for H+/OH− insertion into lipid. This transmembrane condensation model predicts the magnitude of the experimentally determined H+/OH− flux, which is significantly greater than that of other monovalent ions. The consequences of an elevated H+/OH− permeability compared to other ions and the relative pH independence of this flux have consequences for understanding the
chemical evolution of life. 相似文献
9.
Kanakis CD Tarantilis PA Polissiou MG Diamantoglou S Tajmir-Riahi HA 《Cell biochemistry and biophysics》2007,49(1):29-36
In this report we are examining how the antioxidant flavonoids can prevent DNA damage and what mechanism of action is involved
in the process. Flavonoids are strong antioxidants that prevent DNA damage. The anticancer and antiviral activities of these
natural products are implicated in their mechanism of actions. We study the interactions of quercetin (que), kaempferol (kae),
and delphinidin (del) with DNA and transfer RNA in aqueous solution at physiological conditions, using constant DNA or RNA
concentration 6.25 mmol (phosphate) and various pigment/polynucleotide(phosphate) ratios of 1/65 to 1 (DNA) and 1/48 to 1/8
(tRNA). The structural analysis showed quercetin, kaempferol, and delphinidin intercalate DNA and RNA duplexes with minor
external binding to the major or minor groove and the backbone phosphate group with overall binding constants for DNA adducts
K
que = 7.25 (±0.65) × 104 M−1, K
kae = 3.60 (±0.33) × 104 M−1, and K
del = 1.66 (±0.25) × 104 M−1 and for tRNA adducts K
que = 4.80 (±0.50) × 104 M−1, K
kae = 4.65 (±0.45) × 104 M−1, and K
del = 9.47 (±0.70) × 104 M−1. The stability of adduct formation is in the order of del>que>kae for tRNA and que>kae>del for DNA. Low flavonoid concentration
induces helical stabilization, whereas high pigment content causes helix opening. A partial B to A-DNA transition occurs at
high drug concentration, while tRNA remains in A-family structure. The antioxidant activity of flavonoids changes in order
delphinidin>quercetin>kaempferol. The results show intercalated flavonoids can make them strong antioxidants to protect DNA
from harmful free radical reactions. 相似文献
10.
Roger Miras Isabelle Morin Florent Guillain Elisabeth Mintz 《Journal of biological inorganic chemistry》2008,13(2):195-205
Copper is both an essential element as a catalytic cofactor and a toxic element because of its redox properties. Once in the
cell, Cu(I) binds to glutathione (GSH) and various thiol-rich proteins that sequester and/or exchange copper with other intracellular
components. Among them, the Cu(I) chaperone Atx1 is known to deliver Cu(I) to Ccc2, the Golgi Cu–ATPase, in yeast. However,
the mechanism for Cu(I) incorporation into Atx1 has not yet been unraveled. We investigated here a possible role of GSH in
Cu(I) binding to Atx1. Yeast Atx1 was expressed in Escherichia coli and purified to study its ability to bind Cu(I). We found that with an excess of GSH [at least two GSH/Cu(I)], Atx1 formed
a Cu(I)-bridged dimer of high affinity for Cu(I), containing two Cu(I) and two GSH, whereas no dimer was observed in the absence
of GSH. The stability constants (log β) of the Cu(I) complexes measured at pH 6 were 15–16 and 49–50 for CuAtx1 and Cu2I(GS−)2(Atx1)2, respectively. Hence, these results suggest that in vivo the high GSH concentration favors Atx1 dimerization and that Cu2I(GS−)2(Atx1)2 is the major conformation of Atx1 in the cytosol. 相似文献
11.
Kim CH Hong MJ Park SD Kim CK Park MY Sohn HJ Cho HI Kim TG Hong YK 《Cancer immunology, immunotherapy : CII》2006,55(11):1309-1319
Aim: The aim of this study was to develop an immunotherapy specific to a malignant glioma by examining the efficacy of glioma tumor-specific cytotoxic T lymphocytes (CTL) as well as the anti-tumor immunity by vaccination with dendritic cells (DC) engineered to express murine IL-12 using adenovirus-mediated gene transfer and pulsed with a GL26 glioma cell lysate (AdVIL-12/DC+GL26) was investigated. Experimentl: For measuring CTL activity, splenocytes were harvested from the mice immunized with AdVIL-12/DC+GL26 and restimulated with syngeneic GL26 for 7 days. The frequencies of antigen-specific cytokine-secreting T cell were determined with mIFN-γ ELISPOT. The cytotoxicity of CTL was assessed in a standard 51Cr-release assay. For the protective study in the subcutaneous tumor model, the mice were vaccinated subcutaneously (s.c) with 1×106 AdVIL-12/DC+GL26 in the right flanks on day −21, −14 and −7. On day 7, the mice were challenged with 1×106 GL26 tumor cells in the shaved left flank. For a protective study in the intracranial tumor model, the mice were vaccinated with 1×106 AdVIL-12/DC+GL26 s.c in the right flanks on days −21, −14 and −7. Fresh 1×104 GL26 cells were inoculated into the brain on day 0. To prove a therapeutic benefit in established tumors, subcutaneous or intracranial GL26 tumor-bearing mice were vaccinated s.c with 1×106 AdVIL-12/DC+GL26 on day 5, 12 and 19 after tumor cell inoculation. Results: Splenocytes from the mice vaccinated with the AdVIL-12/DC+GL26 showed enhanced induction of tumor-specific CTL and increased numbers of IFN-γ: secreting T cells by ELISPOT. Moreover, vaccination of AdVIL-12/DC+GL26 enhanced the induction of anti-tumor immunity in both the subcutaneous and intracranial tumor models. Conclusions: These preclinical model results suggest that DC engineered to express IL-12 and pulsed with a tumor lysate could be used in a possible immunotherapeutic strategy for malignant glioma.Korea Research Foundation Grant (KRF-2004-005-E00001). 相似文献
12.
Katrin Kuehnle Maria D. Ledesma Lucie Kalvodova Alicia E. Smith Arames Crameri Fabienne Skaanes-Brunner Karin M. Thelen Luka Kulic Dieter Lütjohann Frank L. Heppner Roger M. Nitsch M. Hasan Mohajeri 《Neurochemical research》2009,34(6):1167-1182
Cholesterol is a prominent modulator of the integrity and functional activity of physiological membranes and the most abundant
sterol in the mammalian brain. DHCR24-knock-out mice lack cholesterol and accumulate desmosterol with age. Here we demonstrate
that brain cholesterol deficiency in 3-week-old DHCR24−/− mice was associated with altered membrane composition including disrupted detergent-resistant membrane domain (DRM) structure.
Furthermore, membrane-related functions differed extensively in the brains of these mice, resulting in lower plasmin activity,
decreased β-secretase activity and diminished Aβ generation. Age-dependent accumulation and integration of desmosterol in
brain membranes of 16-week-old DHCR24−/− mice led to the formation of desmosterol-containing DRMs and rescued the observed membrane-related functional deficits. Our
data provide evidence that an alternate sterol, desmosterol, can facilitate processes that are normally cholesterol-dependent
including formation of DRMs from mouse brain extracts, membrane receptor ligand binding and activation, and regulation of
membrane protein proteolytic activity. These data indicate that desmosterol can replace cholesterol in membrane-related functions
in the DHCR24−/− mouse.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
An erratum to this article can be found at 相似文献
13.
Yamaguchi M Hamamoto R Uchiyama S Ishiyama K 《Molecular and cellular biochemistry》2007,303(1-2):83-88
The effect of various flavonoids, which are present in food and plants, on bone calcium content and osteoclastogenesis were
investigated to compare action of flavonoid on bone formation and bone resorption in vitro. Rat femoral-diaphyseal (cortical
bone) and -metaphyseal (trabecular bone) tissues were cultured for 48 h in Dulbecco’s modified Eagle’s medium (high glucose)
supplemented with antibiotics and bovine serum albumin. Amoung quercetin, myricetin, kaempferol, isorhamnetin, curcumin, hesperidin,
or astaxanthin in the range of 10−7–10−5 M, culture with quercetin (10−6 or 10−5 M) caused a significant increase in diaphyseal calcium content. Such an effect was not seen in other compounds. Mouse bone
marrow cells were cultured for 7 days in the presence of parathyroid hormone (PTH; 10−7 M), a bone-resorbing factor, in vitro. Culture with PTH caused a significant increase in osteoclast-like cell formation. This
increase was significantly inhibited in the presence of quercetin, myricetin, kaempferol, isorhamnetin, or curcumin in the
range of 10−8–10−6 M. Such an effect was not seen in the case of hesperidin or astaxanthin. In addition, culture with PTH (10−7 M) caused a significant decrease in diaphyseal calcium content. This decrease was completely prevented in the presence of
quercetin, myricetin, kaempferal, or isorhamnetin of 10−6 M. This study demonstrates that various flavonoids have a potent inhibitory effect on osteoclastogenesis and bone resorption
rather than bone formation in vitro. Among various flavonoids, quercetin had a stimulatory effect on bone formation and an
inhibitory effect on bone resorption in vitro. 相似文献
14.
CCN2 (Connective Tissue Growth Factor) is essential for extracellular matrix production and integrin signaling in chondrocytes 总被引:2,自引:0,他引:2
Nishida T Kawaki H Baxter RM Deyoung RA Takigawa M Lyons KM 《Journal of cell communication and signaling》2007,1(1):45-58
The matricellular protein CCN2 (Connective Tissue Growth Factor; CTGF) is an essential mediator of ECM composition, as revealed through analysis of Ccn2 deficient mice. These die at birth due to complications arising from impaired endochondral ossification. However, the mechanism(s)
by which CCN2 mediates its effects in cartilage are unclear. We investigated these mechanisms using Ccn2
−/−
chondrocytes. Expression of type II collagen and aggrecan were decreased in Ccn2
−/− chondrocytes, confirming a defect in ECM production. Ccn2
−/−
chondrocytes also exhibited impaired DNA synthesis and reduced adhesion to fibronectin. This latter defect is associated
with decreased expression of α5 integrin. Moreover, CCN2 can bind to integrin α5β1 in chondrocytes and can stimulate increased
expression of integrin α5. Consistent with an essential role for CCN2 as a ligand for integrins, immunofluorescence and Western
blot analysis revealed that levels of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK)1/2 phosphorylation
were reduced in Ccn2
−/−
chondrocytes. These findings argue that CCN2 exerts major effects in chondrocytes through its ability to (1) regulate ECM
production and integrin α5 expression, (2) engage integrins and (3) activate integrin-mediated signaling pathways. 相似文献
15.
Grzelak A Kruszewski M Macierzyńska E Piotrowski Ł Pułaski Ł Rychlik B Bartosz G 《Cellular & molecular biology letters》2009,14(1):23-34
The erythrocytes of 12-month old Sod1
−/−
mice showed an increased level of reactive oxygen species (ROS), as estimated by the degree of dihydroethidine and dihydrorhodamine
oxidation, and the increased level of Heinz bodies. No indices of severe oxidative stress were found in the red blood cells
and blood plasma of Sod1
−/−
mice as judged from the lack of significant changes in the levels of erythrocyte and plasma glutathione, plasma protein thiol
and carbonyl groups and thiobarbituric-acid reactive substances in the blood plasma. However, a decreased erythrocyte lifespan,
increased reticulocyte count and splenomegaly were noted, indicating the importance of superoxide dismutase for maintaining
erythrocyte viability. The levels of erythrocyte ROS and Heinz bodies and the reticulocyte count were indistinguishable in
Sod1
+/+
and Sod1
+/−
mice, suggesting that a superoxide dismutase activity decrease to half of its normal value may be sufficient to secure the
protective effects of the enzyme. 相似文献
16.
Guenterberg KD Lesinski GB Mundy-Bosse BL Karpa VI Jaime-Ramirez AC Wei L Carson WE 《Cancer immunology, immunotherapy : CII》2011,60(9):1281-1288
Interferon-alpha (IFN-α) is an immunomodulatory cytokine that is used clinically for the treatment of melanoma in the adjuvant
setting. The cellular actions of IFN-α are regulated by the suppressors of cytokine signaling (SOCS) family of proteins. We
hypothesized that the anti-tumor activity of exogenous IFN-α would be enhanced in SOCS1-deficient mice. SOCS1-deficient (SOCS1−/−) or control (SOCS1+/+) mice on an IFN-γ−/− C57BL/6 background bearing intraperitoneal (i.p.) JB/MS murine melanoma cells were treated for 30 days with i.p. injections
of IFN-A/D or PBS (vehicle). Log-rank Kaplan-Meier survival curves were used to evaluate survival. Tumor-bearing control SOCS1+/+ mice receiving IFN-A/D had significantly enhanced survival versus PBS–treated mice (P = 0.0048). The anti-tumor effects of IFN-A/D therapy were significantly enhanced in tumor-bearing SOCS1−/− mice; 75% of these mice survived tumor challenge, whereas PBS-treated SOCS1−/− mice all died at 13-16 days (P = 0.00038). Antibody (Ab) depletion of CD8+ T cells abrogated the anti-tumor effects of IFN-A/D in SOCS1−/− mice as compared with mice receiving a control antibody (P = 0.0021). CD4+ T-cell depletion from SOCS1−/− mice also inhibited the effects of IFN-A/D (P = 0.0003). IFN-A/D did not alter expression of CD80 or CD86 on splenocytes of SOCS1+/+ or SOCS1−/− mice, or the proportion of T regulatory cells or myeloid-derived suppressor cells in SOCS1+/+ or SOCS1−/− mice. An analysis of T-cell function did reveal increased proliferation of SOCS1-deficient splenocytes at baseline and in
response to mitogenic stimuli. These data suggest that modulation of SOCS1 function in T-cell subsets could enhance the anti-tumor
effects of IFN-α in the setting of melanoma. 相似文献
17.
Christopher Bolton Elizabeth G. Wood Gwen S. Scott Roderick J. Flower 《Cellular and molecular neurobiology》2009,29(5):707-717
The potent oxidant peroxynitrite (ONOO−) is formed after the combination of nitric oxide with superoxide and has been closely associated with the pathology of inflammatory
disease. In particular, the generation of ONOO− has been linked to central nervous system disorders including Alzheimer’s and Parkinson’s disease, multiple sclerosis and
bacterial and viral meningitis. Specifically, ONOO− has been implicated in the loss of blood–brain barrier (BBB) integrity during neuroinflammation, but the precise mechanisms
through which the molecule acts to mediate neurovascular breakdown have not been established. The disruptive effects of ONOO− could be mediated by either direct or indirect actions on the endothelial cells that comprise the major component of the
BBB. The current study has comparatively assessed the direct toxic effects of ONOO− on the brain endothelial cell line, b.End3 and C6 astrocytoma and NA neuroblastoma preparations. b.End3 cells were relatively
resistant to ONOO−-induced cell death compared with C6 and NA cultures. The indirect involvement of ONOO− in neuroendothelial disruption was pharmacologically determined via adhesion molecule expression and immunocompetent cell
attachment to b.End3 cells. ONOO−-targeted drugs, including the selective free radical scavenger, uric acid, the decomposition catalyst 5,10,15,20-tetrakis
(4-sulphonatophenyl) porphyrinatoiron (III) (FeTPPS) and the poly(ADP-ribose) polymerase inhibitor N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-(N,N-dimethylamino) acetamide hydrochloride (PJ34) revealed that ONOO− was only partly involved in E-selectin, ICAM-1 and VCAM-1 expression on b.End3 cells and also cytokine-induced T-lymphocyte
attachment to the cell line. The results indicate that ONOO− contributes to b.End3 cell disruption but is not exclusively responsible for the breakdown of neuroendothelial function. 相似文献
18.
To clarify the neuroprotective property of ceruloplasmin and the pathogenesis of aceruloplasminemia, we generated ceruloplasmin-deficient
(CP
−/−) mice on the C57BL/10 genetic background and further treated them with a mitochondrial complex I inhibitor, rotenone. There
was no iron accumulation in the brains of CP
−/− mice at least up to 60 weeks of age. Without rotenone treatment, CP
−/− mice showed slight motor dysfunction compared with CP
+/+ mice, but there were no detectable differences in the levels of oxidative stress markers between these two groups. A low
dose of rotenone did not affect the mitochondrial complex I activity in our mice, however, it caused a significant change
in motor behavior, neuropathology, or the levels of oxidative stress markers in CP
−/− mice, but not in CP
+/+ mice. Our data support that ceruloplasmin protects against rotenone-induced oxidative stress and neurotoxicity, probably
through its antioxidant properties independently of its function of iron metabolism. 相似文献
19.
Gerard Leblondel Yves Mauras Annie Cailleux Pierre Allain 《Biological trace element research》2001,83(3):191-206
The transport and uptake of the most common Se compounds, selenate (SeO
4
2−
), selenite (SeO
3
2−
), selenomethionine, and selenocystine, were investigated using confluent monolayers of Caco-2 cells, a human carcinoma cell
line. Comparative measurements were performed in the absorptive (apical to basolateral side) and exsorptive (basolateral to
apical side) directions. Apparent permeability coefficients (P
app), calculated from transport experiments in the absorptive direction, showed increasing values in the following rank order:
about 1×10−6 cm/s ≤ mannitol ≤ SeO
3
2−
≤ selenocystine < selenomethionine < SeO
4
2−
≤ about 16×10−6 cm/s. The ratios of the P
app measured in the absorptive versus exsorptive directions indicated that only the organic forms presented a net polarized transport
(P
app ratio ≫1), suggesting the presence of a transcellular pathway. No significant excretion was observed. The transport of selenomethionine
was inhibited by its sulfur analog, methionine, suggesting a common transport mechanism. In contrast, an inhibition of the
transport of selenocystine by cysteine was not observed. From the two substrates tested, sulfate and thiosulfate, only thiosulfate
inhibited the transport of SeO
4
2−
. This effect was also observed for SeO
3
2−
(i.e., was unspecific), which questioned the assertion of a common transport for sulfate and SeO
4
2−
and may confirm the paracellular pathway of SeO
4
2−
suggested by the P
app ratio of about 1. The addition of glutathione (GSH) in large excess had no consequence on the passage of SeO
3
2−
but strongly increased the uptake (about fourfold). The liquid chromatography — mass spectrometry (LC-MS) data showed that,
in the ionic condition of incubation medium, GSH promptly reduced SeO
3
2−
(≤2 min) in its elemental form Se0, which cannot ascribe to selenodiglutathione a direct role in the effect of GSH. 相似文献
20.
Jacoby Arie S. Holmes Fiona E. Hort Yvonne J. Shine John Iismaa Tiina P. 《International journal of peptide research and therapeutics》2001,8(3-5):139-146
Summary The GALR1 galanin receptor is expressed at high levels within the central nervous system and is hypothesised to play a significant
role in many of the central actions of galanin. To determine which specific actions of galanin are mediated by GALR1, we have
developed mice that carry an insertional inactivating mutation within the first coding exon of the gene encoding GALR1 (Galr1). HomozygousGalr1
−/− mice are viable. Both male and female mice exhibit reduced circulating levels of insulin-like growth factor-I (IGF-I) but
no significant difference in growth rate relative toGalr1
+/+ controls. Female homozygousGalr1
−/− mice are capable of breeding and nursing offspring. Functional recovery after sciatic nerve crush is not significantly different
inGalr1
−/− mice relative toGalr1
+/+ controls, indicating that GALR1 does not mediate the nerve regenerative effects of galanin. However, homozygousGalr1
−/− mice exhibit spontaneous seizures, identifying a critical role for GALR1 in mediating the anti-seizure activity of galanin. 相似文献