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The 68K protease has beta-secretase-like activity for lymphocyte precursor protein but not for brain substrate.

https://arctichealth.org/en/permalink/ahliterature199515
Source
Neuroreport. 2000 Feb 7;11(2):373-7
Publication Type
Article
Date
Feb-7-2000
Author
A. Matsumoto
Author Affiliation
Department of Radiation Biophysics and Genetics, Kobe University School of Medicine, Japan.
Source
Neuroreport. 2000 Feb 7;11(2):373-7
Date
Feb-7-2000
Language
English
Publication Type
Article
Keywords
Aged
Aged, 80 and over
Alzheimer Disease - enzymology
Amino Acid Sequence
Amyloid Precursor Protein Secretases
Amyloid beta-Protein Precursor - metabolism
Aspartic Acid Endopeptidases - metabolism
Blotting, Western
Cells, Cultured
Cerebral Cortex - enzymology
Chondroitin ABC Lyase - metabolism
Endopeptidases
Female
Humans
Isoenzymes - metabolism
Lymphocytes - cytology - enzymology
Male
Middle Aged
Molecular Sequence Data
Organ Specificity
Peptide Fragments - chemistry
Polysaccharide-Lyases - metabolism
Protein Processing, Post-Translational
Sequence Analysis, Protein
Serine Endopeptidases - metabolism
Substrate Specificity
Abstract
Processing and metabolism of beta-amyloid precursor protein (APP) and generation of a variety of beta-amyloid (Abeta) peptides in the human brain is essentially associated with pathophysiology of Alzheimer's disease (AD). APP degradation activity of the 68 kDa serine protease, which was originally prepared from familial AD lymphoblastoid cells and harbors beta-secretase-like activity, was analyzed by Western blot using anti Abeta 1/40 antibody and anti APP cytoplasmic domain (CT) antibody. Native lymphocyte APP (LAPP) prepared from normal or AD-derived lymphoblastoid cells was degraded by the protease, generating a 16 kDa Abeta-bearing C-terminal fragment of APP. N-terminal amino acid sequencing of the fragment indicated that the protease cleaves LAPP at the Abeta-N-terminus. When the LAPP was treated with chondroitinase ABC prior to proteolysis, the activity to generate the fragment was inhibited, but pretreatment with heparitinase resulted in no effect. Native hippocampal APP prepared from normal brain, however, did not generate the 16 kDa peptide by the protease treatment. These results suggest that the process of APP degradation and Abeta-peptides generation, including beta-secretase activity, is associated with tissue specificity of both APP substrate and proteases. They also indicate that sulfated glycoconjugates attached to a portion of APP isoforms may play a role as a molecular determinant in the proteolysis.
PubMed ID
10674489 View in PubMed
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Antenatal drugs affecting vitamin K status of the fetus and the newborn.

https://arctichealth.org/en/permalink/ahliterature23368
Source
Semin Thromb Hemost. 1995;21(4):364-70
Publication Type
Article
Date
1995
Author
B. Astedt
Author Affiliation
Department of Obstetrics and Gynecology, University Hospital, Lund, Sweden.
Source
Semin Thromb Hemost. 1995;21(4):364-70
Date
1995
Language
English
Publication Type
Article
Keywords
Abnormalities, Drug-Induced - etiology
Anticoagulants - adverse effects - pharmacokinetics
Anticonvulsants - adverse effects - pharmacokinetics
Blood Coagulation Factors - metabolism
Child
Cohort Studies
Coumarins - adverse effects - pharmacokinetics
Epilepsy - drug therapy
Female
Fetal Diseases - chemically induced
Great Britain - epidemiology
Hemorrhage - chemically induced
Humans
Infant, Newborn
Maternal-Fetal Exchange
Neoplasms - chemically induced - epidemiology
Pregnancy
Pregnancy Complications - drug therapy
Prenatal Exposure Delayed Effects
Protein Processing, Post-Translational
Research Support, Non-U.S. Gov't
Sweden - epidemiology
Thrombosis - drug therapy
Vitamin K - adverse effects - physiology - therapeutic use
Vitamin K Deficiency - chemically induced - embryology - prevention & control
Abstract
Coumarin derivatives and anticonvulsants administered during pregnancy enter the fetal circulation, interfering with the action of vitamin K. Vitamin K plays a crucial part in the gamma-carboxylation of glutamic acid residues of the vitamin K-dependent coagulation factors prothrombin, FVII, FIX, and FX. Other vitamin K-dependent proteins in the coagulation cascade are protein C and protein S. Vitamin K-dependent bone proteins are osteocalcin and gamma-carboxyglutamate matrix protein. Administration of coumarol derivatives results in under carboxylation of the vitamin K-dependent proteins. Anticoagulation therapy with warfarin is followed by an increased risk of embryopathy, which has been shown to be greatest between gestational weeks 6 and 12. Administration of warfarin is also followed by an increased risk both of fetal intraventricular hemorrhage, and of cerebral microbleedings, which may result in microencephaly and mental retardation. Treatment with coumarol derivatives should therefore be avoided during pregnancy, even in pregnant women with artificial heart valves, and replaced by heparin. Hemorrhage in the newborn related to the use of anticonvulsant drugs during pregnancy occurs very early within the first 24 hours, probably due to increased degradation of vitamin K. Transplacental administration of vitamin K has been shown to prevent neonatal hemorrhage induced by maternal anticonvulsant therapy. Prophylactic administration of vitamin K, especially by intramuscular injection, has been reported to be associated with an increased risk of childhood cancer. However, subsequent extensive studies have yielded no evidence of any relationship between prophylactic vitamin K administration and the occurrence of childhood cancer.
PubMed ID
8747699 View in PubMed
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[A procedure for determining the oxidative modification of apolipoproteins in low-density lipoproteins]

https://arctichealth.org/en/permalink/ahliterature83771
Source
Klin Lab Diagn. 2007 Jun;(6):14-7
Publication Type
Article
Date
Jun-2007
Author
Ragino Iu I
Polonskaia Ia V
Sadovskii E V
Source
Klin Lab Diagn. 2007 Jun;(6):14-7
Date
Jun-2007
Language
Russian
Publication Type
Article
Keywords
Aged
Apolipoproteins - blood
Biological Markers - blood
Coronary Arteriosclerosis - blood
Humans
Lipoproteins, LDL - blood
Male
Middle Aged
Oxidation-Reduction
Oxidative Stress
Protein Processing, Post-Translational
Reproducibility of Results
Siberia
Spectrophotometry, Ultraviolet
Abstract
The purpose of the present study was to develop a new procedure for estimating the oxidative modification of apolipoproteins in low-density lipoproteins (LDLs). The procedure was developed to use blood serum from 153 males aged 45-65 years, including 69 patients with coronary angiography-verified coronary atherosclerosis and 84 males from a representative sample from Novosibirsk residents of the same age. The new procedure is as follows: a rapid method for isolating serum LDLs, their apolipoprotein (apoLP) protein measurement by the Lowry procedure, their precipitation, a reaction with 2,4-dinitrophenylhydrazine in 2 M HCl solution, by subsequently rinsing in the ethanol:ethyl acetate (1:1) solution, dissolving the precipitate in 8 M urea, and by determining the level of the resultant dinitrophenylhydrazones by spectrophotometry at 363 nm, followed by conversion to LDL concentration of apoLP. The procedure is of informative value for the degree of oxidative LDL modification of apoLP under oxidative stress; it is technically simple, takes little time, and shows a good reproducibility. The values of determined oxidized LDL apoLP by the developed procedure highly positively correlated with the estimates of an oxidized total blood protein fraction and with the values of endothelial dysfunction and did not with the parameters of blood LDL peroxidation. The detected elevated oxidation LDL apoLP in males with coronary atherosclerosis suggests that this index is an additional marker of potentially atherogenic LDL changes.
PubMed ID
17682473 View in PubMed
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Collaboration between centres of the World Health Organization. Italy supports a Mexican university.

https://arctichealth.org/en/permalink/ahliterature138745
Source
Med Lav. 2010 Nov-Dec;101(6):453-7
Publication Type
Article
Author
J. Alegria-Torres
A. Baccarelli
Author Affiliation
Departamento de Toxicologia Ambiental, Facultad de Medicina, Universidad Autonoma de San Luis Potosi, Mexico.
Source
Med Lav. 2010 Nov-Dec;101(6):453-7
Language
English
Publication Type
Article
Keywords
Academic Medical Centers - organization & administration
Acetylation
Biological Markers - analysis
Child
Child Welfare
Child, Preschool
DNA Methylation
Environmental Health - organization & administration
Environmental Pollutants - adverse effects
Genetic Predisposition to Disease
Health Status Indicators
Histones - chemistry
Humans
Infant
International Cooperation
Methylation
Mexico
MicroRNAs - analysis - genetics
Protein Processing, Post-Translational
Vulnerable Populations
World Health Organization - organization & administration
Abstract
Mexico is the third most populous country in America. A sizeable percentage of Mexicans live under unfavorable conditions such as malnutrition, marginalization and overcrowding. Environmental injustice includes: indigenous exposed to wood smoke, families living in mining zones, children working and living in garbage dumps and brick factories. Polycyclic aromatic hydrocarbons, pesticides, electronic waste and heavy metals exposure represent a health risk. These pollutants can induce biochemical lesions as DNA damage and epigenetic changes which could modif the gene expression profile of each individual.
The aim of this work is to create an Italy-Mexico collaboration (within the context of WHO collaborating centres) between the Center of Molecular and Genetic Epidemiology, University of Milan and the University of San Luis Potosi, will allow molecular approaches to develop early indicators of susceptibility to adult disease and cancer.
PubMed ID
21141348 View in PubMed
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Covalent protein adducts in the liver as a result of ethanol metabolism and lipid peroxidation.

https://arctichealth.org/en/permalink/ahliterature11580
Source
Lab Invest. 1994 Apr;70(4):537-46
Publication Type
Article
Date
Apr-1994
Author
O. Niemelä
S. Parkkila
S. Ylä-Herttuala
C. Halsted
J L Witztum
A. Lanca
Y. Israel
Author Affiliation
Department of Clinical Chemistry, Univeristy of Oulu, Finland.
Source
Lab Invest. 1994 Apr;70(4):537-46
Date
Apr-1994
Language
English
Publication Type
Article
Keywords
Acetaldehyde - chemistry
Alcoholism - metabolism
Animals
Ethanol - metabolism - pharmacology
Hepatitis, Alcoholic - metabolism - pathology
Humans
Immunologic Techniques
Lipid Peroxides - metabolism
Liver - metabolism
Malondialdehyde - chemistry
Protein Processing, Post-Translational
Proteins - chemistry
Rats
Rats, Sprague-Dawley
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Swine
Swine, Miniature
Abstract
BACKGROUND: The primary mechanisms of ethanol-induced tissue damage have been suggested to include aldehyde-derived protein modifications resulting from ethanol metabolism and lipid peroxidation. Conjugation of reactive aldehydes to a variety of target proteins and cellular constituents have been recently reported. This research was undertaken in order to examine the presence of covalent chemical addition products (adducts) of proteins and acetaldehyde, the first metabolite of ethanol, and those with malondialdehyde, a product of lipid peroxidation, as formed in vivo. EXPERIMENTAL DESIGN: Specific antibodies recognizing acetaldehyde- and malondialdehyde-modified epitopes in proteins were used in immunoperoxidase and double immunofluorescence stainings of liver specimens obtained from ethanol-fed rats and micropigs and from human alcoholics. RESULTS: The centrilobular region of the liver contained the protein modifications both in alcohol-consuming humans and in animals fed ethanol before any apparent histologic damage. With inflammation and fibrosis, such protein modifications were more widespread, and the positive staining for the malondialdehyde-derived modification became more dominant. The presence of the adducts colocalized with the areas of fatty infiltration, focal necrosis and fibrosis. In addition, the erythrocytes of alcohol consumers were found to contain such modifications. CONCLUSIONS: The studies support the view that covalent damage to proteins and cellular constituents induced by aldehyde-derived modifications in vivo may play a role in the sequence of events leading to liver disease in alcohol consumers. Species and dietary differences may be important in the relative contribution of lipid peroxidation to alcohol-induced tissue damage.
PubMed ID
8176892 View in PubMed
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Effects of divergent resistance exercise contraction mode and dietary supplementation type on anabolic signalling, muscle protein synthesis and muscle hypertrophy.

https://arctichealth.org/en/permalink/ahliterature263594
Source
Amino Acids. 2014 Oct;46(10):2377-92
Publication Type
Article
Date
Oct-2014
Author
Stine Klejs Rahbek
Jean Farup
Andreas Buch Møller
Mikkel Holm Vendelbo
Lars Holm
Niels Jessen
Kristian Vissing
Source
Amino Acids. 2014 Oct;46(10):2377-92
Date
Oct-2014
Language
English
Publication Type
Article
Keywords
Adult
Denmark
Dietary Carbohydrates - administration & dosage
Dietary Supplements
Double-Blind Method
Energy Metabolism
Exercise
Humans
Male
Milk Proteins - administration & dosage
Muscle Contraction
Muscle Development
Muscle Proteins - biosynthesis
Muscle, Skeletal - metabolism
Phosphorylation
Protein Processing, Post-Translational
Resistance Training
Signal Transduction
Young Adult
Abstract
Greater force produced with eccentric (ECC) compared to concentric (CONC) contractions, may comprise a stronger driver of muscle growth, which may be further augmented by protein supplementation. We investigated the effect of differentiated contraction mode with either whey protein hydrolysate and carbohydrate (WPH + CHO) or isocaloric carbohydrate (CHO) supplementation on regulation of anabolic signalling, muscle protein synthesis (MPS) and muscle hypertrophy. Twenty-four human participants performed unilateral isolated maximal ECC versus CONC contractions during exercise habituation, single-bout exercise and 12 weeks of training combined with WPH + CHO or CHO supplements. In the exercise-habituated state, p-mTOR, p-p70S6K, p-rpS6 increased by approximately 42, 206 and 213 %, respectively, at 1 h post-exercise, with resistance exercise per se; whereas, the phosphorylation was exclusively maintained with ECC at 3 and 5 h post-exercise. This acute anabolic signalling response did not differ between the isocaloric supplement types, neither did protein fractional synthesis rate differ between interventions. Twelve weeks of ECC as well as CONC resistance training augmented hypertrophy with WPH + CHO group compared to the CHO group (7.3 ± 1.0 versus 3.4 ± 0.8 %), independently of exercise contraction type. Training did not produce major changes in basal levels of Akt-mTOR pathway components. In conclusion, maximal ECC contraction mode may constitute a superior driver of acute anabolic signalling that may not be mirrored in the muscle protein synthesis rate. Furthermore, with prolonged high-volume resistance training, contraction mode seems less influential on the magnitude of muscle hypertrophy, whereas protein and carbohydrate supplementation augments muscle hypertrophy as compared to isocaloric carbohydrate supplementation .
PubMed ID
25005782 View in PubMed
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Effects of the amyloid precursor protein Glu693-->Gln 'Dutch' mutation on the production and stability of amyloid beta-protein.

https://arctichealth.org/en/permalink/ahliterature201872
Source
Biochem J. 1999 Jun 15;340 ( Pt 3):703-9
Publication Type
Article
Date
Jun-15-1999
Author
D J Watson
D J Selkoe
D B Teplow
Author Affiliation
Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women's Hospital, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Source
Biochem J. 1999 Jun 15;340 ( Pt 3):703-9
Date
Jun-15-1999
Language
English
Publication Type
Article
Keywords
Amino Acid Sequence
Amino Acid Substitution
Amyloid beta-Peptides - chemistry - genetics - metabolism
Amyloid beta-Protein Precursor - chemistry - genetics - metabolism
Amyloidosis - genetics
Cell Line
Cerebral Hemorrhage - genetics
Culture Media, Conditioned - chemistry - metabolism
Glutamic Acid - genetics - metabolism
Glutamine - genetics - metabolism
Humans
Molecular Sequence Data
Molecular Weight
Netherlands
Peptide Fragments - chemistry - metabolism
Precipitin Tests
Protein Processing, Post-Translational
Sequence Analysis
Sweden
Time Factors
Abstract
Hereditary cerebral haemorrhage with amyloidosis, Dutch type (HCHWA-D), is a cerebral amyloidosis characterized by prominent vascular deposits and fatal haemorrhages. The disorder is caused by a point mutation in codon 693 of the gene encoding the amyloid precursor protein (APP), resulting in a Glu-->Gln amino acid substitution at position 22 of the amyloid beta-protein (Abeta) region. The pathogenetic mechanisms of HCHWA-D are unknown but could involve alterations in the proteolytic processing of APP and in amyloid fibril formation. We examined Abeta production and stability by using cultured human embryonic kidney 293 cells stably expressing wild-type or 'Dutch' APP. Radiosequencing and quantitative immunoprecipitation experiments showed that cells expressing Dutch APP secreted increased quantities of Abeta peptides beginning at Asp1, and of truncated peptides beginning at Val18 and Phe19. The ratio of levels of 4 kDa (Abeta) to 3 kDa (p3) peptides remained constant due to co-ordinate decreases in other peptide species. Novel truncated or elongated peptides were not observed. Pulse-chase experiments showed that the Dutch mutation did not affect the stability of the Abeta or p3 populations. These results are consistent with a disease process in which the Dutch mutation results in the production of Abeta peptides with enhanced propensities for fibrillogenesis, leading to accelerated vascular deposition and disease.
Notes
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PubMed ID
10359654 View in PubMed
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Elevated Golgi pH impairs terminal N-glycosylation by inducing mislocalization of Golgi glycosyltransferases.

https://arctichealth.org/en/permalink/ahliterature89702
Source
J Cell Physiol. 2009 Jul;220(1):144-54
Publication Type
Article
Date
Jul-2009
Author
Rivinoja Antti
Hassinen Antti
Kokkonen Nina
Kauppila Annika
Kellokumpu Sakari
Author Affiliation
Department of Biochemistry and The Finnish Glycoscience Graduate School, University of Oulu, Oulu, Finland.
Source
J Cell Physiol. 2009 Jul;220(1):144-54
Date
Jul-2009
Language
English
Publication Type
Article
Keywords
Animals
COS Cells
Carcinoembryonic Antigen - metabolism
Cercopithecus aethiops
Chloroquine - pharmacology
Dose-Response Relationship, Drug
Endosomes - enzymology
Galactosyltransferases - metabolism
Glycosylation
Glycosyltransferases - genetics - metabolism
Golgi Apparatus - drug effects - enzymology
Hydrogen-Ion Concentration
Lysosomes - enzymology
Mannosidases - metabolism
Mutation
Protein Processing, Post-Translational - drug effects
Protein Structure, Tertiary
Protein Transport
Recombinant Fusion Proteins - metabolism
Sialyltransferases - metabolism
Time Factors
Transfection
Abstract
Acidic pH of the Golgi lumen is known to be crucial for correct glycosylation, transport and sorting of proteins and lipids during their transit through the organelle. To better understand why Golgi acidity is important for these processes, we have examined here the most pH sensitive events in N-glycosylation by sequentially raising Golgi luminal pH with chloroquine (CQ), a weak base. We show that only a 0.2 pH unit increase (20 microM CQ) is sufficient to markedly impair terminal alpha(2,3)-sialylation of an N-glycosylated reporter protein (CEA), and to induce selective mislocalization of the corresponding alpha(2,3)-sialyltransferase (ST3) into the endosomal compartments. Much higher pH increase was required to impair alpha(2,6)-sialylation, or the proximal glycosylation steps such as beta(1,4)-galactosylation or acquisition of Endo H resistance, and the steady-state localization of the key enzymes responsible for these modifications (ST6, GalT I, MANII). The overall Golgi morphology also remained unaltered, except when Golgi pH was raised close to neutral. By using transmembrane domain chimeras between the ST6 and ST3, we also show that the luminal domain of the ST6 is mainly responsible for its less pH sensitive localization in the Golgi. Collectively, these results emphasize that moderate Golgi pH alterations such as those detected in cancer cells can impair N-glycosylation by inducing selective mislocalization of only certain Golgi glycosyltransferases.
PubMed ID
19277980 View in PubMed
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Expression of the mature luteinizing hormone receptor in rodent urogenital and adrenal tissues is developmentally regulated at a posttranslational level.

https://arctichealth.org/en/permalink/ahliterature63225
Source
Endocrinology. 2005 Aug;146(8):3224-32
Publication Type
Article
Date
Aug-2005
Author
Pirjo M Apaja
Jyrki T Aatsinki
Hannu J Rajaniemi
Ulla E Petäjä-Repo
Author Affiliation
Biocenter Oulu and Department of Anatomy and Cell Biology, University of Oulu, FI-90014 Oulu, Finland. ulla.petaja-repo@oulu.fi
Source
Endocrinology. 2005 Aug;146(8):3224-32
Date
Aug-2005
Language
English
Publication Type
Article
Keywords
Adrenal Glands - growth & development - physiology
Animals
Cell Differentiation
DNA Primers
Female
Fetal Development
Gene Expression Regulation, Developmental - physiology
Genes, Reporter
Gestational Age
Kidney - physiology
Mice
Mice, Transgenic
Ovary - embryology - physiology
Pregnancy
Promoter Regions (Genetics)
Protein Processing, Post-Translational
RNA, Messenger - genetics
Rats
Rats, Sprague-Dawley
Receptors, LH - genetics - metabolism
Research Support, Non-U.S. Gov't
Reverse Transcriptase Polymerase Chain Reaction
Up-Regulation
Abstract
The LH receptor (LHR) is a G protein-coupled receptor involved in the regulation of ovarian and testicular functions. In this study we demonstrate novel and unexpected patterns of receptor expression and regulation in fetal and adult rodent urogenital and adrenal tissues. Two rat LHR promoter fragments (approximately 2 and 4 kb) were shown to direct expression of the lacZ reporter in transgenic mice to gonads, adrenal glands, and kidneys, starting at 14.5 d post coitum, and to genital tubercles, starting at 11.5 d post coitum. These tissues were also found to express the full-length LHR mRNA and protein during rat fetal development, but, importantly, only immature receptors carrying unprocessed N-linked glycans were detected. After birth, the receptor gene activity ceased, except in the gonads, which started to express the mature receptor carrying fully processed N-linked glycans. Surprisingly, both LHR mRNA and mature protein levels were up-regulated substantially in pregnant female adrenal glands and kidneys at a time that coincides with differentiation of fetal urogenital tissues. Taken together, these results indicate that the LHR protein is expressed constitutively in gonadal and nongonadal urogenital tissues as well in adrenal glands, but its final functional maturation at the posttranslational level appears to be developmentally and physiologically regulated.
Notes
Comment In: Endocrinology. 2005 Aug;146(8):3221-316009970
PubMed ID
15860556 View in PubMed
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Fibrin(ogen) may be an important target for methylglyoxal-derived AGE modification in elastic arteries of humans.

https://arctichealth.org/en/permalink/ahliterature132147
Source
Diab Vasc Dis Res. 2011 Oct;8(4):284-94
Publication Type
Article
Date
Oct-2011
Author
Terje Lund
Aud Svindland
Milaim Pepaj
Aase-Brith Jensen
Jens P Berg
Bente Kilhovd
Kristian F Hanssen
Author Affiliation
Department of Endocrinology – Section Hormone Laboratory, Oslo University Hospital, Norway. terjelu@medisin.uio.no
Source
Diab Vasc Dis Res. 2011 Oct;8(4):284-94
Date
Oct-2011
Language
English
Publication Type
Article
Keywords
Aged
Aged, 80 and over
Amino Acid Sequence
Aorta - chemistry - pathology
Blotting, Western
Carotid Artery, Common - chemistry - pathology
Case-Control Studies
Chromatography, Liquid
Diabetic Angiopathies - metabolism - pathology
Elasticity
Female
Fibrin - analysis
Fibrinogen - analysis
Glycosylation End Products, Advanced - analysis
Humans
Imidazoles - analysis
Immunohistochemistry
Male
Middle Aged
Molecular Sequence Data
Necrosis
Norway
Protein Processing, Post-Translational
Proteomics - methods
Pyruvaldehyde - analysis
Tandem Mass Spectrometry
Abstract
Diabetes is associated with increased risk of cardiovascular disease. Advanced glycation end-products (AGEs) are considered to be a major pathogenic factor for diabetic vascular complications. The levels of AGEs are increased in diabetic patients. We have studied the presence of the major AGE methylglyoxal (MGO)-derived hydroimidazolone in human aorta and carotid arteries, using immunohistochemistry (IHC), western blotting and mass spectrometry. By IHC, MGO-derived modifications were detected mainly associated with cells in intimal thickenings and cells in microvessels in adventitia. In type V lesions MGO-derived AGE was also present, extracellular in the necrotic core and in cells at the border of the core. The highest degree of modification was probably associated with cell nuclei. By western blotting and mass spectrometry fibrin(ogen), the cytoskeleton-associated protein moesin and the nuclear proteins lamin A and C were identified as putative main targets for MGO-derived modification. LC-MS/MS studies of fibrin(ogen) modified in vitro with low concentrations of MGO identified the sites that were most prone to modification. These results indicate that AGE modifications occur preferentially on specific proteins. The modification of these proteins may play a role in vascular dysfunction and development of atherosclerosis in diabetes.
PubMed ID
21844128 View in PubMed
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21 records – page 1 of 3.