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181.
Al-Ramahi I Lam YC Chen HK de Gouyon B Zhang M Pérez AM Branco J de Haro M Patterson C Zoghbi HY Botas J 《The Journal of biological chemistry》2006,281(36):26714-26724
CHIP (C terminus of Hsc-70 interacting protein) is an E3 ligase that links the protein folding machinery with the ubiquitin-proteasome system and has been implicated in disorders characterized by protein misfolding and aggregation. Here we investigate the role of CHIP in protecting from ataxin-1-induced neurodegeneration. Ataxin-1 is a polyglutamine protein whose expansion causes spinocerebellar ataxia type-1 (SCA1) and triggers the formation of nuclear inclusions (NIs). We find that CHIP and ataxin-1 proteins directly interact and co-localize in NIs both in cell culture and SCA1 postmortem neurons. CHIP promotes ubiquitination of expanded ataxin-1 both in vitro and in cell culture. The Hsp70 chaperone increases CHIP-mediated ubiquitination of ataxin-1 in vitro, and the tetratricopeptide repeat domain, which mediates CHIP interactions with chaperones, is required for ataxin-1 ubitiquination in cell culture. Interestingly, CHIP also interacts with and ubiquitinates unexpanded ataxin-1. Overexpression of CHIP in a Drosophila model of SCA1 decreases the protein steady-state levels of both expanded and unexpanded ataxin-1 and suppresses their toxicity. Finally we investigate the ability of CHIP to protect against toxicity caused by expanded polyglutamine tracts in different protein contexts. We find that CHIP is not effective in suppressing the toxicity caused by a bare 127Q tract with only a short hemagglutinin tag, but it is very efficient in suppressing toxicity caused by a 128Q tract in the context of an N-terminal huntingtin backbone. These data underscore the importance of the protein framework for modulating the effects of polyglutamine-induced neurodegeneration. 相似文献
182.
Antioxidant activity in Spalax ehrenbergi: a possible adaptation to underground stress 总被引:1,自引:0,他引:1
Beatriz Caballero Cristina Tomás-Zapico Ignacio Vega-Naredo Verónica Sierra Delio Tolivia Rüdiger Hardeland María Josefa Rodríguez-Colunga Alma Joel Eviatar Nevo Aaron Avivi Ana Coto-Montes 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2006,192(7):753-759
The blind subterranean mole rat Spalax ehrenbergi superspecies has evolved adaptive strategies to cope with underground stress. Hypoxia is known to stimulate reactive oxygen species generation; however, mechanisms by which Spalax counteracts oxidative damage have not been investigated before. We studied in Spalax the oxidative status of the Harderian gland (HG), an organ which is particularly vulnerable to oxidative stress in many rodents. With regard to the sexual dimorphism found in this gland, differences between males and females were determined and compared to the surface-dwelling Syrian hamster. Our results show, for the first time, that Spalax exhibits remarkably low biomolecular damage, which implies the existence of physiological strategies to avoid oxidative damage under fluctuating O2 and CO2 levels existing in the mole rat’s subterranean niche. Correspondingly, main antioxidant enzymes, such as superoxide dismutase (SOD), catalase, and glutathione reductase (GR), exhibited high activities in both genders; in particular, remarkably high levels were measured in SOD. SOD and GR activities showed statistically significant differences between sexes. Melatonin, an important circadian agent is also a very important antioxidant molecule and is synthesized in the Harderian glands (HGs) of Spalax. Therefore, the possible interaction between antioxidant enzymes and melatonin is suggested.Joint senior authorship: Aaron Avivi and Ana Coto-Montes 相似文献
183.
Fernandez MC Castaño A Dominguez E Escribano A Jiang D Jimenez A Hong E Hornback WJ Nisenbaum ES Rankl N Tromiczak E Vaught G Zarrinmayeh H Zimmerman DM 《Bioorganic & medicinal chemistry letters》2006,16(19):5057-5061
The synthesis and initial SAR studies of novel, highly potent positive allosteric modulators of AMPA receptors based on 3-(4-tert-butylphenyl)-4-cyano-5-methylsulfanyl-thiophene-2-carboxylic acid (6a) are described. SAR studies at the thioether moiety indicated that substitution at this position was mandatory and better potency was achieved with small groups. 相似文献
184.
Ana Lucía De Paul Andrs Maximiliano Attademo Ruben Walter Carn Marta Soaje Alicia Ins Torres Graciela Alma Jahn María Ester Celis 《Peptides》2009,30(11):2081
The neuropeptide EI (NEI) is derived from proMCH. It activates GnRH neurons, and has been shown to stimulate the LH release following intracerebroventricular administration in several experimental models. The aim of the present paper was to evaluate NEI actions on pituitary hormone secretion and cell morphology in vitro. Pituitary cells from female rats were treated with NEI for a wide range of concentrations (1–400 × 10−8 M) and time periods (1–5 h). The media were collected and LH, FSH, PRL, and GH measured by RIA. The interaction between NEI (1, 10 and 100 × 10−8 M) and GnRH (0.1 and 1 × 10−9 M) was also tested. Pituitary cells were harvested for electron microscopy, and the immunogold immunocytochemistry of LH was assayed after 2 and 4 h of NEI incubation. NEI (100 × 10−8 M) induced a significant LH secretion after 2 h of stimulus, reaching a maximum response 4 h later. A rapid and remarkable LH release was induced by NEI (400 × 10−8 M) 1 h after stimulus, attaining its highest level at 2 h. However, PRL, GH and FSH were not affected. NEI provoked ultrastructural changes in the gonadotrophs, which showed accumulations of LH-immunoreactive granules near the plasma membrane and exocytotic images, while the other populations exhibited no changes. Although NEI (10 × 10−8 M), caused no action when used alone, its co-incubation with GnRH (1 × 10−9 M), promoted a slight but significant increase in LH. These results demonstrate that NEI acts at the pituitary level through a direct action on gonadotrophs, as well as through interaction with GnRH. 相似文献
185.
Alma Balestrazzi Silvia Botti Samantha Zelasco Stefania Biondi Cinzia Franchin Paolo Calligari Milvia Racchi Adelaide Turchi Guido Lingua Graziella Berta Daniela Carbonera 《Plant cell reports》2009,28(8):1179-1192
Marker-free transgenic white poplar (Populus alba L., cv ‘Villafranca’) plants, expressing the PsMT
A1
gene from Pisum sativum for a metallothionein-like protein, were produced by Agrobacterium tumefaciens-mediated transformation. The 35SCaMV-PsMT
A1
-NosT cassette was inserted into the ipt-type vector pMAT22. The occurrence of the abnormal ipt-shooty phenotype allowed the visual selection of transformants, while the yeast site-specific recombination R/RS system was
responsible for the excision of the undesired vector sequences with the consequent recovery of normal marker-free transgenic
plants. Molecular analyses confirmed the presence of the 35SCaMV-PsMT
A1
-NosT cassette and transgene expression. Five selected lines were further characterized, revealing the ability to withstand
heavy metal toxicity. They survived 0.1 mM CuCl2, a concentration which strongly affected the nontransgenic plants. Moreover, root development was only slightly affected
by the ectopic expression of the transgene. Reactive oxygen species were accumulated to a lower extent in leaf tissues of
multi-auto-transformation (MAT)-PsMTA1 plants exposed to copper and zinc, compared to control plants. Tolerance to photo-oxidative stress induced by paraquat was
another distinctive feature of the MAT-PsMTA1 lines. Finally, low levels of DNA damage were detected by quantifying the amounts of 8-hydroxy-2′-deoxyguanosine in leaf
tissues of the transgenic plants exposed to copper. 相似文献
186.
187.
188.
Pituitary adenylate cyclase-activating polypeptide (PACAP) 38 is a multifunctional anti-inflammatory and anti-apoptotic neuropeptide widely distributed in the nervous system. The objective of this study is to determine whether PACAP38 is neuroprotective against sodium nitroprusside (SNP) and thrombin, two mechanistically distinct neurotoxic agents. Treatment of primary cortical neuronal cultures with 1 mM SNP for 4 h causes neuronal cell death that is significantly reduced by 100 nM PACAP38. PACAP38 down-regulates SNP-induced cell cycle protein (cyclin E) expression and up-regulates p57(KIP2), a cyclin-dependent kinase inhibitor as well as the anti-apoptotic protein Bcl-2. Similarly, neuronal death induced by 100 nM thrombin or the thrombin receptor activating peptide (TRAP 6) is reduced by PACAP38 treatment. Thrombin-stimulated cell cycle protein (cdk4) expression is decreased by PACAP38 while PACAP38 inhibits thrombin-mediated reduction of p57(KIP2). However, the decrease in Bcl-2 evoked by thrombin is not affected by PACAP38. Finally, both SNP and thrombin (or TRAP) increase caspase 3 activity, an effect that is decreased by PACAP38. These data show that PACAP38 supports neuronal survival in vitro suppressing cell cycle progression and enhancing anti-apoptotic proteins. Our results support the possibility that PACAP could be a useful therapeutic agent for reducing neuronal cell death in neurodegenerative diseases. 相似文献
189.
Sonja Fraas Alma K. Steinbach Anja Tabbert Jens Harder Ulrich Ermler Kai Tittmann Axel Meyer Peter M.H. Kroneck 《Journal of Molecular Catalysis .B, Enzymatic》2009,61(1-2):47
Alicyclic alcohols are naturally occurring compounds which can be degraded by microorganisms via cleavage of the ring C–C bond. Denitrifying Azoarcus sp. strain 22Lin grows on cyclohexane-1,2-diol which serves as electron donor and carbon source. The diol is converted to cyclohexane-1,2-dione followed by hydrolysis to the corresponding semialdehyde and oxidation to adipate. The latter two reactions are catalyzed by the thiamine diphosphate-dependent flavoenzyme cyclohexane-1,2-dione hydrolase, the first α-ketolase known so far. Biochemical and structural properties of this new member of the thiamine diphosphate enzyme family will be presented. 相似文献
190.
Massimo Confalonieri † Maria Cammareri † Elisa Biazzi † Paola Pecchia Manuel Pedro Salema Fevereiro Alma Balestrazzi Aldo Tava Clara Conicella 《Plant biotechnology journal》2009,7(2):172-182
Triterpene saponins are a group of bioactive compounds abundant in the genus Medicago , and have been studied extensively for their biological and pharmacological properties. In this article, we evaluated the effects of the ectopic expression of AsOXA1 cDNA from Aster sedifolius on the production of triterpene saponins in barrel medic ( Medicago truncatula Gaertn.). AsOXA1 cDNA encodes β-amyrin synthase, a key enzyme involved in triterpene saponin biosynthesis. One of the four transgenic lines expressing AsOXA1 accumulated significantly larger amounts of some triterpenic compounds in leaf and root than did control plants. In particular, the leaf exhibited significantly higher levels of bayogenin, medicagenic acid and zanhic acid. The amounts of medicagenic acid and zanhic acid, which represent the core of the M. truncatula leaf saponins, were 1.7 and 2.1 times higher, respectively, than the amounts extracted from the control line. In root, the production of bayogenin, hederagenin, soyasapogenol E and 2β-hydroxyoleanolic acid was increased significantly. The increase in the total amounts of triterpenic compounds observed in the leaves of transgenic lines correlated with the AsOXA1 expression level. Interestingly, the plants expressing AsOXA1 showed, under different growth conditions, improved nodulation when compared with the control line. Nodulation enhancement was also accompanied by a significant change in the soyasapogenol B content. Our results indicate that the ectopic expression of AsOXA1 in barrel medic leads to a greater accumulation of triterpene saponins and enhanced root nodulation. 相似文献