Abstract:
:Parkinson's disease (PD) involves loss of dopaminergic neurons in the substantia nigra and is characterized by intracellular inclusions, Lewy bodies, consisting primarily of aggregated alpha-synuclein. Two substitution mutations (A53T and A30P) in alpha-synuclein gene have been identified in familial early-onset PD. To understand the biological changes that incur upon alpha-synuclein-induced cytotoxicity in the presence of dopamine, the current studies were undertaken. Human SH-SY5Y neuroblastoma cells coexpressing the human dopamine transporter [hDAT], and either wild type (wt) or mutant alpha-synucleins, were treated with 50 microM dopamine (DA). In cells expressing wt or A30P alpha-synuclein, DA accelerated production of reactive oxygen species and cell death as compared to cells expressing A53T or hDAT alone. The increased sensitivity of such cells to DA was investigated by measuring changes in cellular ionic gradient, by atomic absorption spectrometry, and cell metabolism, by high-resolution nuclear magnetic resonance spectroscopy. Both wt and A30P alpha-synuclein caused rapid decrease in levels of intracellular potassium, followed by mitochondrial damage and cytochrome c leakage, with decreased cellular metabolism as compared to cells expressing A53T or hDAT alone. Collapse of ionic gradient was significantly faster in A30P (t(1/2) = 3.5 h) than in wt (t(1/2) = 6.5 h) cells, and these changes in ionic gradient preceded cytochrome c leakage and depletion of metabolic energy. Neither wt nor mutant alpha-synuclein resulted in significant changes in ionic gradient or cellular metabolism in the absence of intracellular DA. These findings suggest a specific sequence of events triggered by dopamine and differentially exacerbated by alpha-synuclein and the A30P mutant.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Moussa CE,Wersinger C,Tomita Y,Sidhu Adoi
10.1021/bi036114fsubject
Has Abstractpub_date
2004-05-11 00:00:00pages
5539-50issue
18eissn
0006-2960issn
1520-4995journal_volume
43pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::PHD2 is a 2-oxoglutarate, non-heme Fe(2+)-dependent oxygenase that senses O2 levels in human cells by hydroxylating two prolyl residues in the oxygen-dependent degradation domain (ODD) of HIF1α. Identifying the active site contacts that determine the rate of reaction at limiting O2 concentrations is crucial for unders...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi501540c
更新日期:2015-05-12 00:00:00
abstract::Lon is a homo-oligomeric ATP-dependent serine protease that functions in the degradation of damaged and certain regulatory proteins. This enzyme has emerged as a novel target in the development of antibiotics because of its importance in conferring bacterial virulence. In this study, we explored the mechanism by which...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi7002789
更新日期:2007-06-05 00:00:00
abstract::A Rhodobacter sphaeroides bchD (magnesium chelatase) mutant was studied to determine the properties of its photosystem in the absence of bacteriochlorophyll (BChl). Western blots of reaction center H, M, and L (RC H/M/L) proteins from mutant membranes showed levels of 12% RC H, 32% RC L, and 46% RC M relative to those...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi701407k
更新日期:2007-10-30 00:00:00
abstract::The functional interaction of the recombinant alpha 2 adrenergic receptor subtypes, alpha 2-C10 (the human platelet alpha 2 receptor, equivalent to the alpha 2 A subtype) and alpha 2-C4 (an alpha 2 receptor subtype cloned from a human kidney cDNA library), with G proteins was characterized in an in vitro reconstitutio...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00227a024
更新日期:1991-04-02 00:00:00
abstract::The NADH absorbance spectrum of nicotinoprotein (NADH-containing) alcohol dehydrogenase from Amycolatopsis methanolica has a maximum at 326 nm. Reduced enzyme-bound pyridine dinucleotide could be reversibly oxidized by acetaldehyde. The fluorescence excitation spectrum for NADH bound to the enzyme has a maximum at 325...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi972115u
更新日期:1998-03-03 00:00:00
abstract::The dioxygen stretch bands in infrared spectra for solutions of oxy species of human hemoglobin A and its separated subunits, human mutant hemoglobin Zurich (beta 63His to Arg), rabbit hemoglobin, lamprey hemoglobin, sperm whale myoglobin, bovine myoglobin, and a sea worm chlorocruorin are examined. Each protein exhib...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00389a016
更新日期:1987-07-28 00:00:00
abstract::The mechanisms that control N protein dependent antitermination in phage lambda have counterparts in many eukaryotic systems, including specific regulatory interactions of the antitermination protein with the nascent RNA transcript. Here we describe the specific and nonspecific RNA binding modes of antitermination pro...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi961920q
更新日期:1997-02-11 00:00:00
abstract::Several snake venoms contain a phospholipase A2 in which position 49 in the active site is occupied by a lysine or a serine instead of the aspartate residue normally found. Although these proteins do not bind Ca2+ and are devoid of catalytic activity, they are still highly specific myotoxins and have recently been sho...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00014a021
更新日期:1995-04-11 00:00:00
abstract::[15N]Glycine was biosynthetically incorporated into normal cellular N-ras p21 and a position 12 transforming mutant, in order to produce p21 proteins containing several site-specific NMR probes at or near activating positions in the guanine nucleotide binding domain. We have previously assigned all five glycine resona...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00450a035
更新日期:1989-11-28 00:00:00
abstract::The solution conformation of the DNA duplex d(C1G2C3A4C5L6C7A8C9G10C11).d(G12C13G14T15G16T17G18T19G20C21G22 ) containing the 2'-deoxyribonolactone lesion (L6) in the middle of the sequence has been investigated by NMR spectroscopy and restrained molecular dynamics calculations. Interproton distances have been obtained...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi982743r
更新日期:1999-03-30 00:00:00
abstract::The second-order rate constants for the reactions between nitrogen monoxide and oxymyoglobin or oxyhemoglobin, determined by stopped-flow spectroscopy, increase with increasing pH. At pH 7.0 the rates are (43.6 +/- 0.5) x 10(6) M(-1) x s(-1) for oxymyoglobin and (89 +/- 3) x 10(6) M(-1) x s(-1) for oxyhemoglobin (per ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi002407m
更新日期:2001-03-20 00:00:00
abstract::In the absence of any external electron donor, the "peroxy" intermediate of cytochrome c oxidase (CcO-607) is converted to the ferryl form (CcO-580) and subsequently to oxidized enzyme. The rate of conversion of CcO-607 to the CcO-580 form is pH dependent between pH 3.0 and pH 7.6. A plot of the logarithm of the rate ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi002373i
更新日期:2001-02-13 00:00:00
abstract::Eicosanoids have been implicated in the regulation of arterial smooth muscle cell (SMC) cholesteryl ester (CE) metabolism. These eicosanoids, which include prostacyclin (PGI2), stimulate CE hydrolytic activities. High-density lipoproteins (HDL), which promote cholesterol efflux, also stimulate PGI2 production, suggest...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00459a033
更新日期:1990-02-20 00:00:00
abstract::In the reaction center (RC) of the photosynthetic bacterium Rhodobacter sphaeroides, two ubiquinone molecules, QA and QB, play a pivotal role in the conversion of light energy into chemical free energy by coupling electron transfer to proton uptake. In native RCs, the transfer of an electron from QA to QB takes place ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi700297b
更新日期:2007-04-17 00:00:00
abstract::The transglutaminase Factor XIII (FXIII) catalyzes the formation of covalent cross-links between adjacent noncovalently associated fibrin chains in blood coagulation. The resulting covalently cross-linked hard clot is much more mechanically stable and resistant to proteolytic degradation. FXIII is activated by the ser...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi049260+
更新日期:2004-08-03 00:00:00
abstract::D-Xylose isomerase (XI) is a heat-stable homotetrameric enzyme used in industry for the production of high-fructose corn syrups by isomerization of D-glucose into D-fructose. To carry out biochemical and structural studies of this enzyme and of its engineered variants, a rapid and convenient method of purification of ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00125a009
更新日期:1992-03-17 00:00:00
abstract::The hairpin catalytic motif in tobacco ringspot virus satellite RNA consists of two helix-loop-helix elements on two adjacent arms of a four-way helical junction. The bases essential for catalytic activity are located in the loops that are brought into proximity by a conformational change as a prerequisite for catalys...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi010773f
更新日期:2001-09-18 00:00:00
abstract::High-resolution 2D NMR spectra of the duplex CGCGAATTCGCG with deoxyribose sugars but with the normal phosphodiester linker replaced by an N3' --> P5' phosphoramidate (NP) group have been used to establish a solution structure for the duplex. Distance, angle, and base pair hydrogen-bonding constraints were used to ref...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi980711y
更新日期:1998-09-01 00:00:00
abstract::The reduction of substrates catalyzed by nitrogenase normally requires nucleotide-dependent Fe protein delivery of electrons to the MoFe protein, which contains the active site FeMo cofactor. Here, it is reported that independent substitution of three amino acids (β-98(Tyr→His), α-64(Tyr→His), and β-99(Phe→His)) locat...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.5b00140
更新日期:2015-04-21 00:00:00
abstract::Time-resolved infrared (TRIR) techniques have been employed to study the reactions of carbon monoxide with the cytochrome alpha 3-Cu(B) site of cytochrome c oxidase (CcO). The ligation dynamics immediately following photodissociation have been investigated using picosecond TRIR spectroscopy and linear dichroism. The r...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00168a015
更新日期:1994-01-18 00:00:00
abstract::The aureolic acid antitumor antibiotic mithramycin (MTM) inhibits both cancer growth and bone resorption by cross-linking GC-rich DNA, thus blocking binding of Sp-family transcription factors to gene regulatory elements. Transcription of c-src, a gene implicated in many human cancers and required for osteoclast-depend...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi034091z
更新日期:2003-07-15 00:00:00
abstract::G.U pairs occur frequently and have many important biological functions. The stability of symmetric tandem G.U motifs depends both on the adjacent Watson-Crick base pairs, e.g., 5'G > 5'C, and the sequence of the G.U pairs, i.e., 5'-UG-3' > 5'-GU-3', where an underline represents a nucleotide in a G.U pair [Wu, M., Mc...
journal_title:Biochemistry
pub_type: 杂志文章
doi:
更新日期:2000-08-01 00:00:00
abstract::Apo horse spleen ferritin (apo HoSF) was reconstituted to various core sizes (100-3500 Fe3+/HoSF) by depositing Fe(OH)3 within the hollow HoSF interior by air oxidation of Fe2+. Fe2+ and phosphate (Pi) were then added anaerobically at a 1:4 ratio, and both Fe2+ and Pi were incorporated into the HoSF cores. The resulti...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi982727u
更新日期:1999-05-18 00:00:00
abstract::In eukaryotes, choline acetyltransferase (ChAT) catalyzes the reversible formation of the neurotransmitter acetylcholine from choline and acetyl-CoA. ChAT belongs to a family of CoA-dependent enzymes that also includes the carnitine acyltransferases CrAT, CrOT, and CPTs. In contrast to CrOT and CPTs that are very acti...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi1007996
更新日期:2010-07-27 00:00:00
abstract::Neuronal PAS protein 2 (NPAS2), a heme-binding transcriptional regulatory factor, is involved in circadian rhythms. Period homologue (Per) is another important transcriptional regulatory factor that binds to cryptochrome (Cry). The resultant Per/Cry heterodimer interacts with the NPAS2/BMAL1 heterodimer to inhibit the...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi7023892
更新日期:2008-06-10 00:00:00
abstract::In Campylobacter jejuni 2,4-diacetamido-2,4,6-trideoxy-alpha-d-glucopyranose, termed N,N'-diacetylbacillosamine (Bac2,4diNAc), is the first carbohydrate in the glycoprotein N-linked heptasaccharide. With uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) as a starting point, two enzymes of the general protein glycos...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi061456h
更新日期:2006-11-14 00:00:00
abstract::Little is known about the extent to which protein flexibility contributes to antigen-antibody recognition and cross-reactivity. Using short coil peptides (leucine zippers) as model antigens, we demonstrate that a monoclonal antibody can force a noncognate peptide into a conformation that is similar to the conformation...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00050a035
更新日期:1995-12-19 00:00:00
abstract::Protein misfolding due to missense mutations is a common pathogenic mechanism in cystathionine β-synthase (CBS) deficiency. In our previous studies, we successfully expressed, purified, and characterized nine CBS mutant enzymes containing the following patient mutations: P49L, P78R, A114V, R125Q, E176K, R266K, P422L, ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi300435e
更新日期:2012-06-12 00:00:00
abstract::The reaction of Pseudomonas fluorescens kynureninase with L-kynurenine and L-alanine has been examined using rapid-scanning stopped-flow spectrophotometry. Mixing kynureninase with 0.5 mM L-kynurenine results in formation of a quinonoid intermediate, with lambdamax = 494 nm, within the dead time (ca. 2 ms) of the stop...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi980066v
更新日期:1998-06-16 00:00:00
abstract::Snake venom contains a number of the hemostatically active C-type lectin-like proteins, which affect the interaction between von Willebrand factor (vWF) and the platelet glycoprotein (GP) Ib or platelet receptor to inhibit/induce platelet activation. Flavocetin-A (FL-A) is a high-molecular mass C-type lectin-like prot...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi992134z
更新日期:2000-02-29 00:00:00