Abstract:
:Peroxiredoxins (Prx), a family of peroxidases that reduce intracellular peroxides with the thioredoxin system as the electron donor, are highly expressed in various cellular compartments. Among the antioxidant Prx enzymes, Prx2 is the most abundant in mammalian neurons, making it a prime candidate to defend against oxidative stress. Here we report that Prx2 is S-nitrosylated (forming SNO-Prx2) by reaction with nitric oxide at two critical cysteine residues (C51 and C172), preventing its reaction with peroxides. We observed increased SNO-Prx2 in human Parkinson's disease (PD) brains, and S-nitrosylation of Prx2 inhibited both its enzymatic activity and protective function from oxidative stress. Dopaminergic neurons, which are lost in PD, become particularly vulnerable. Thus, our data provide a direct link between nitrosative/oxidative stress and neurodegenerative disorders such as PD.
journal_name
Proc Natl Acad Sci U S Aauthors
Fang J,Nakamura T,Cho DH,Gu Z,Lipton SAdoi
10.1073/pnas.0705904104subject
Has Abstractpub_date
2007-11-20 00:00:00pages
18742-7issue
47eissn
0027-8424issn
1091-6490pii
0705904104journal_volume
104pub_type
杂志文章abstract::The locus control region of the beta-globin gene is composed of four erythroid-specific hypersensitive sites. Hypersensitive site 2 has been shown to be a powerful enhancer and contains a tandem repeat sequence for the transcription factors AP1 and NFE2 (activating protein 1 and nuclear factor erythroid 2, respectivel...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.24.13943
更新日期:1996-11-26 00:00:00
abstract::In the filamentous fungus Neurospora crassa, several events in the process of conidiation are influenced by light. Two genes, con-6 and con-10, which were previously shown to be transcriptionally activated during conidiation and by exposure to light, were found to be unexpressed in mycelium maintained in constant dark...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.17.8249
更新日期:1993-09-01 00:00:00
abstract::Serum RNase (ribonuclease) of normal persons and of patients with pancreatitis, carcinoma of pancreas, or other neoplasms was determined with poly(C) as substrate. Strikingly abnormal elevations occur in the serum RNase of patients with pancreatic cancer. There is no elevation in the serum RNase level of patients with...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.73.7.2308
更新日期:1976-07-01 00:00:00
abstract::Ascorbic acid, at nontoxic concentrations, causes a substantial reduction in the ability of avian tumor viruses to replicate in both primary avian tendon cells and chicken embryo fibroblasts. The virus-infected cultures appear to be less transformed in the presence of ascorbic acid by the criteria of morphology, reduc...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.5.2711
更新日期:1980-05-01 00:00:00
abstract::The active conformation of native peroxisomal 3-ketoacyl-CoA thiolases (EC 2.3.1.16) is homodimeric. We have previously shown that a truncated Saccharomyces cerevisiae thiolase lacking its first 16 N-terminal amino acids fails to be translocated into peroxisomes but assembles into an enzymatically active form in the c...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.22.10541
更新日期:1994-10-25 00:00:00
abstract::Humans and other primates are distinct among placental mammals in having exceptionally slow rates of growth, reproduction, and aging. Primates' slow life history schedules are generally thought to reflect an evolved strategy of allocating energy away from growth and reproduction and toward somatic investment, particul...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1316940111
更新日期:2014-01-28 00:00:00
abstract::We introduce Pathifier, an algorithm that infers pathway deregulation scores for each tumor sample on the basis of expression data. This score is determined, in a context-specific manner, for every particular dataset and type of cancer that is being investigated. The algorithm transforms gene-level information into pa...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1219651110
更新日期:2013-04-16 00:00:00
abstract::Many "workers" in north temperate colonies of the eusocial paper wasp Polistes fuscatus disappear within a few days of eclosion. We provide evidence that these females are pursuing an alternative reproductive strategy, i.e., dispersing to overwinter and become nest foundresses the following spring, instead of helping ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.23.13737
更新日期:1998-11-10 00:00:00
abstract::Inorganic elements, although required only in trace amounts, permit life and primary productivity because of their functions in catalysis. Every organism has a minimal requirement of each metal based on the intracellular abundance of proteins that use inorganic cofactors, but elemental sparing mechanisms can reduce th...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1422492112
更新日期:2015-03-03 00:00:00
abstract::An enzymatic activity, having the properties expected of a B-specific host-controlled modification enzyme, has been purified from an extract of Escherichia coli strain B. This activity renders the unmodified replicative form of phage fd resistant to B-specific restriction and is only present in strains carrying intact...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.63.2.556
更新日期:1969-06-01 00:00:00
abstract::The "false thumb" of pandas is a carpal bone, the radial sesamoid, which has been enlarged and functions as an opposable thumb. If the giant panda (Ailuropoda melanoleuca) and the red panda (Ailurus fulgens) are not closely related, their sharing of this adaptation implies a remarkable convergence. The discovery of pr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0504899102
更新日期:2006-01-10 00:00:00
abstract::Prion protein consists of an ensemble of glycosylated variants or glycoforms. The enzymes that direct oligosaccharide processing, and hence control the glycan profile for any given glycoprotein, are often exquisitely sensitive to other events taking place within the cell in which the glycoprotein is expressed. Alterat...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.23.13044
更新日期:1999-11-09 00:00:00
abstract::In human adults, learning and memory under acute stress are characterized by an increased use of rigid habitual response strategies at the cost of flexible cognitive strategies. The immediate effects of stress on cognitive functioning early in life are not well understood. Here we show experimentally that acute stress...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 临床试验,杂志文章
doi:10.1073/pnas.1508345112
更新日期:2015-10-13 00:00:00
abstract::Osteoclasts, bone-resorptive multinucleated cells derived from hematopoietic stem cells, are associated with many bone-related diseases, such as osteoporosis. Osteoclast-targeting small-molecule inhibitors are valuable tools for studying osteoclast biology and for developing antiresorptive agents. Here, we have discov...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0712239105
更新日期:2008-08-19 00:00:00
abstract::In the developing CNS, Notch1 and its ligand, Jagged1, regulate oligodendrocyte differentiation and myelin formation, but their role in repair of demyelinating lesions in diseases such as multiple sclerosis remains unresolved. To address this question, we generated a mouse model in which we targeted Notch1 inactivatio...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0902834106
更新日期:2009-11-10 00:00:00
abstract::Because of the relative inaccessibility of known calciferol target tissues (i.e., intestine and bone), we examined fibroblasts derived from normal human skin and grown in tissue culture as a means of evaluating the interaction of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] and its effector system. When dispersed, inta...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.78.4.2562
更新日期:1981-04-01 00:00:00
abstract::In the primary visual cortex, neurons with similar response preferences are grouped into domains forming continuous maps of stimulus orientation and direction of movement. These properties are widely believed to result from the combination of ascending and lateral interactions in the visual system. We have tested this...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.242399199
更新日期:2002-12-24 00:00:00
abstract::Bacillus anthrax lethal toxin can be engineered to deliver foreign proteins to the cytosol for antigen presentation to CD8 T cells. Vaccination with modified toxins carrying 8-9 amino acid peptide epitopes induces protective immunity in mice. To evaluate whether large protein antigens can be used with this system, rec...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.97.14.8027
更新日期:2000-07-05 00:00:00
abstract::A sensitive in vitro crosslinking technique using a photoactive derivative of the chimeric activator LexA-E2F-1 was used to identify yeast proteins that might influence the response of RNA polymerase II to transcriptional activators. We found that a novel yeast protein, Xtc1p, could be covalently crosslinked to the ac...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.19.11122
更新日期:1998-09-15 00:00:00
abstract::The transthyretin amyloidoses (ATTR) are invariably fatal diseases characterized by progressive neuropathy and/or cardiomyopathy. ATTR are caused by aggregation of transthyretin (TTR), a natively tetrameric protein involved in the transport of thyroxine and the vitamin A-retinol-binding protein complex. Mutations with...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1121005109
更新日期:2012-06-12 00:00:00
abstract::Voltage-gated sodium (Na(V)) and potassium (K(V)) channels are critical components of neuronal action potential generation and propagation. Here, we report that Na(V)β1 encoded by SCN1b, an integral subunit of Na(V) channels, coassembles with and modulates the biophysical properties of K(V)1 and K(V)7 channels, but no...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1209142109
更新日期:2012-11-06 00:00:00
abstract::After adrenalectomy, the plasma levels of adrenocorticotropic hormone (corticotropin, ACTH)/endorphin peptides in rats rise dramatically in the first 4 hr while pituitary peptide levels fall sharply. Eight hours after adrenalectomy, plasma levels are near control values again but they then increase continuously over t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.22.6982
更新日期:1983-11-01 00:00:00
abstract::Computers are organized into hardware and software. Using a theoretical approach to identify patterns in gene expression in a variety of species, organs, and cell types, we found that biological systems similarly are comprised of a relatively unchanging hardware-like gene pattern. Orthogonal patterns of software-like ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1200790109
更新日期:2012-03-20 00:00:00
abstract::The trilaminate vascular architecture provides biochemical regulation and mechanical integrity. Yet regulatory control can be regained after injury without recapitulating tertiary structure. Tissue-engineered (TE) endothelium controls repair even when placed in the perivascular space of injured vessels. It remains unc...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0802463105
更新日期:2008-05-13 00:00:00
abstract::The auditory and motor neural systems are closely intertwined, enabling people to carry out tasks such as playing a musical instrument whose mapping between action and sound is extremely sophisticated. While the dorsal auditory stream has been shown to mediate these audio-motor transformations, little is known about h...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 临床试验,杂志文章
doi:10.1073/pnas.1721414115
更新日期:2018-06-26 00:00:00
abstract::pRK212.2, a derivative of the broad host range plasmid RK2, contains two EcoRI cleavage fragments, A and B, neither of which can replicate by itself in Escherichia coli. Fragment A (41.7 kilobases), but not fragment B (14.4 kilobases), can be cloned by insertion into the unrelated plasmids mini-F and ColE1. Fragment B...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.76.4.1648
更新日期:1979-04-01 00:00:00
abstract::Heat shock locus V (HslV; also called ClpQ) is the proteolytic core of the ATP-dependent protease HslVU in Escherichia coli. It has sequence similarity with the beta-type subunits of the eukaryotic and archaebacterial proteasomes. Unlike these particles, which display 72-point symmetry, it is a dimer of hexamers with ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.12.6070
更新日期:1997-06-10 00:00:00
abstract::Night-shift workers are at high risk of drowsiness-related motor vehicle crashes as a result of circadian disruption and sleep restriction. However, the impact of actual night-shift work on measures of drowsiness and driving performance while operating a real motor vehicle remains unknown. Sixteen night-shift workers ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1510383112
更新日期:2016-01-05 00:00:00
abstract::We describe a cell-free system in which the transcription of the yeast metallothionein gene is inducible by the addition of metal ions plus a specific regulatory protein. Efficient transcription requires the complete yeast ACE1 metalloregulatory protein, including both its DNA-binding and transactivation domains; a mo...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.21.8377
更新日期:1989-11-01 00:00:00
abstract::We report the molecular cloning of the first beta-1,3 glucanase from animal tissue. Three peptide sequences were obtained from beta-1,3 glucanase that had been purified from eggs of the sea urchin Strongylocentrotus purpuratus and the gene was cloned by PCR using oligonucleotides deduced from the peptide sequences. Th...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.13.6808
更新日期:1996-06-25 00:00:00