Isoaspartate-containing amyloid precursor protein-derived peptides alter efficacy and specificity of potential beta-secretases.

Abstract:

:Neuritic plaques of Alzheimer patients are composed of multiple protein components. Among them, the amyloid beta-peptides (Abeta) 1-40/42 and further N- and C-terminally modified fragments of Abeta are highly abundant. Most prominent are the isoaspartate (isoAsp)-Abeta peptides and pyroglutamyl (pGlu)-Abeta. While pGlu-Abeta can only be formed from an N-terminal glutamate by glutaminyl cyclase, spontaneous isoAsp-isomerization cannot occur at an N-terminal aspartate of peptides. This means that isoAsp-Abeta formation must precede proteolysis of the amyloid precursor protein (APP). Abeta generation from APP by beta- and gamma-secretases initiates the amyloid peptide aggregation and deposition process. Two aspartate proteases have been identified as secretases: BACE-1 (beta-site amyloid precursor protein cleaving enzyme) and the intramembrane gamma-secretase multiprotein complex. However, recent evidence supports more than one beta-secretase initiating this cascade. Formation of Abeta1-40/42 was predominantly studied by expression of mutated human APP sequences in cell culture and transgenic animals, generating Abeta fragments that did not contain such multiple posttranslational modifications as in Alzheimer's disease. This prompted us to investigate the catalytic turnover of Asp- or isoAsp-containing APP-derived peptide sequences by BACE-1 and cathepsin B, another potential beta-secretase. While cathepsin B is more effective than BACE-1 in processing the Asp-containing peptide derivatives, only cathepsin B can cleave the isoAsp-containing peptides, which occurs with high catalytic efficiency.

journal_name

Biol Chem

journal_title

Biological chemistry

authors

Böhme L,Hoffmann T,Manhart S,Wolf R,Demuth HU

doi

10.1515/BC.2008.125

subject

Has Abstract

pub_date

2008-08-01 00:00:00

pages

1055-66

issue

8

eissn

1431-6730

issn

1437-4315

pii

10.1515/BC.2008.125_bchm.just-accepted

journal_volume

389

pub_type

杂志文章
  • Solubilisation and properties of the sialate-4-O-acetyltransferase from guinea pig liver.

    abstract::The O-acetylation of sialic acids turns out to be one of the most important modifications that influence the diverse biological and pathophysiological properties of glycoconjugates in animals and microorganisms. To understand the functions of this esterification, knowledge of the properties, structures and regulation ...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2003.116

    authors: Iwersen M,Dora H,Kohla G,Gasa S,Schauer R

    更新日期:2003-07-01 00:00:00

  • Ultraviolet B radiation induces cell shrinkage and increases osmolyte transporter mRNA expression and osmolyte uptake in HaCaT keratinocytes.

    abstract::We have previously shown that compatible organic osmolytes, such as betaine, myo-inositol and taurine, are part of the stress response of normal human keratinocytes (NHKs) to ultraviolet B (UVB) radiation. In this regard, we tested human HaCaT keratinocytes as a surrogate cell line for NHK. HaCaT cells osmo-dependentl...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2007.140

    authors: Warskulat U,Brookmann S,Reinen A,Häussinger D

    更新日期:2007-12-01 00:00:00

  • [18O]-labeled singlet oxygen as a tool for mechanistic studies of 8-oxo-7,8-dihydroguanine oxidative damage: detection of spiroiminodihydantoin, imidazolone and oxazolone derivatives.

    abstract::A water-soluble [18O]-labeled endoperoxide derived from N,N'-di(2,3-dihydroxypropyl)-1,4-naphthalene-dipropanamide (DHPN18O2) has been shown to act as a clean chemical source of [18O]-labeled molecular singlet oxygen. This allows the assessment of the singlet oxygen (1O2) reactivity toward biological targets such as D...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2002.063

    authors: Martinez GR,Medeiros MH,Ravanat JL,Cadet J,Di Mascio P

    更新日期:2002-03-01 00:00:00

  • Kinetics of autocatalytic zymogen activation measured by a coupled reaction: pepsinogen autoactivation.

    abstract::A kinetic study was performed of a model for an autocatalytic zymogen activation process involving both intra- and intermolecular routes, to which a chromogenic reaction in which the active enzyme acts upon one of its substrates was coupled to continuously monitor the reaction. Kinetic equations describing the evoluti...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2005.080

    authors: Fuentes ME,Varón R,García-Moreno M,Valero E

    更新日期:2005-07-01 00:00:00

  • Evidence for a protective role of the CX3CL1/CX3CR1 axis in a model of amyotrophic lateral sclerosis.

    abstract::Aberrant microglial activation and neuroinflammation is a pathological hallmark of amyotrophic lateral sclerosis (ALS). Fractalkine (CX3CL1) is mostly expressed on neuronal cells. The fractalkine receptor (CX3CR1) is predominantly expressed on microglia. Many progressive neuroinflammatory disorders show disruption of ...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/hsz-2018-0204

    authors: Liu C,Hong K,Chen H,Niu Y,Duan W,Liu Y,Ji Y,Deng B,Li Y,Li Z,Wen D,Li C

    更新日期:2019-04-24 00:00:00

  • Calcium-sensing receptor: roles in and beyond systemic calcium homeostasis.

    abstract::The cloning of a Ca2+(0)-sensing receptor (CaR) from parathyroid and kidney, coupled with the identification of inherited disorders in Ca2+(0)-sensing resulting from inactivating or activating mutations of this CaR, has provided substantial insights into how Ca2+(0) is regulated at a systemic level. The CaR plays a ce...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:

    authors: Chattopadhyay N,Vassilev PM,Brown EM

    更新日期:1997-08-01 00:00:00

  • Role of sigma 1 receptor in high fat diet-induced peripheral neuropathy.

    abstract::The neurobiological mechanisms of obesity-induced peripheral neuropathy are poorly understood. We evaluated the role of Sigma-1 receptor (Sig-1R) and NMDA receptor (NMDARs) in the spinal cord in peripheral neuropathy using an animal model of high fat diet-induced diabetes. We examined the expression of Sig-1R and NMDA...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/hsz-2017-0117

    authors: Song T,Zhao J,Ma X,Zhang Z,Jiang B,Yang Y

    更新日期:2017-09-26 00:00:00

  • Calpastatin exon 1B-derived peptide, a selective inhibitor of calpain: enhancing cell permeability by conjugation with penetratin.

    abstract::The ubiquitous calpains, mu- and m-calpain, have been implicated in essential physiological processes and various pathologies. Cell-permeable specific inhibitors are important tools to elucidate the roles of calpains in cultivated cells and animal models. The synthetic N-acetylated 27-mer peptide derived from exon B o...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2003.045

    authors: Gil-Parrado S,Assfalg-Machleidt I,Fiorino F,Deluca D,Pfeiler D,Schaschke N,Moroder L,Machleidt W

    更新日期:2003-03-01 00:00:00

  • Dual concentration-dependent activity of thyroglobulin type-1 domain of testican: specific inhibitor and substrate of cathepsin L.

    abstract::The thyroglobulin type-1 (Tg-1) domain is a protein module that occurs in a variety of secreted and membrane proteins and is recognised as a potent inhibitor of cysteine peptidases. We present here some properties of the Tg-1 domain of human testican, a modularly organised proteoglycan secreted mainly by brain cells, ...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2005.010

    authors: Meh P,Pavsic M,Turk V,Baici A,Lenarcic B

    更新日期:2005-01-01 00:00:00

  • Synthetic biology of B cell activation: understanding signal amplification at the B cell antigen receptor using a rebuilding approach.

    abstract::Upon activation of the B cell antigen receptor (BCR), the spleen tyrosine kinase (Syk) and the Src family kinase Lyn phosphorylate tyrosines of the immunoreceptor tyrosine-based activation motif (ITAM) of Igα and Igβ which further serve as binding sites for the SH2 domains of these kinases. Using a synthetic biology a...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/hsz-2018-0308

    authors: Kulathu Y,Zuern C,Yang J,Reth M

    更新日期:2019-03-26 00:00:00

  • Major vault protein is a substrate of endogenous protein kinases in CHO and PC12 cells.

    abstract::Major vault protein (MVP) is the predominant member of a large cytosolic ribonucleoprotein particle, termed vault. We have previously shown that MVP derived from electric ray electric organ becomes phosphorylated by protein kinase C in vitro and by tyrosine kinase in vivo. Here we show that MVP from two mammalian cell...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2001.180

    authors: Ehrnsperger C,Volknandt W

    更新日期:2001-10-01 00:00:00

  • A nucleosome-free dG-dC-rich sequence element promotes constitutive transcription of the essential yeast RIO1 gene.

    abstract::RIO1 is an essential gene that encodes a protein serine kinase and is transcribed constitutively at a very low level. Transcriptional activation of RIO1 dispenses with a canonical TATA box as well as with classical transactivators or specific DNA-binding factors. Instead, a dG-dC-rich sequence element, that is located...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2003.143

    authors: Angermayr M,Schwerdffeger K,Bandlow W

    更新日期:2003-09-01 00:00:00

  • Central nervous system: cholesterol turnover, brain development and neurodegeneration.

    abstract::The average amount of cholesterol in the whole animal equals approximately 2100 mg/kg body weight, and 15% and 23% of this sterol in the mouse and human, respectively, is found in the central nervous system. There is no detectable uptake across the blood-brain barrier of cholesterol carried in lipoproteins in the plas...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/BC.2009.035

    authors: Dietschy JM

    更新日期:2009-04-01 00:00:00

  • Agonist-stimulated pathways of calcium signaling in pancreatic acinar cells.

    abstract::In pancreatic acinar cells stimulation of different intracellular pathways leads to different patterns of Ca2+ signaling. Bombesin induces activation of both phosphatidylinositol 4,5-bisphosphate (PIP2)-specific phospholipase C (PLC) and phospholipase D (PLD). The latter leads to generation of diacylglycerol (DAG) in ...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/BC.1999.111

    authors: Schulz I,Krause E,González A,Göbel A,Sternfeld L,Schmid A

    更新日期:1999-07-01 00:00:00

  • Nervous system pathology: the fibrin perspective.

    abstract::Studies of extracellular matrix (ECM) biology in the nervous system have mainly focused on laminin, fibronectin and tenascin-R, proteins that are present during nervous system development and normal function. However, during disease, fibrin, which physiologically is not present in the nervous tissue, is detected at ne...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/BC.2002.004

    authors: Akassoglou K,Strickland S

    更新日期:2002-01-01 00:00:00

  • Redefining proteostasis transcription factors in organismal stress responses, development, metabolism, and health.

    abstract::Eukaryotic organisms have evolved complex and robust cellular stress response pathways to ensure maintenance of proteostasis and survival during fluctuating environmental conditions. Highly conserved stress response pathways can be triggered and coordinated at the cell-autonomous and cell-nonautonomous level by proteo...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/hsz-2019-0385

    authors: Jones LM,Chen Y,van Oosten-Hawle P

    更新日期:2020-08-27 00:00:00

  • Mechanism of methaemoglobin breakdown by the lysine-specific gingipain of the periodontal pathogen Porphyromonas gingivalis.

    abstract::Abstract The R- and K-gingipain proteases of Porphyromonas gingivalis are involved in proteolysis of haemoglobin from which the defensive dimeric haem pigment is formed. Whilst oxyhaemoglobin is refractory towards K-gingipain, methaemoglobin is rapidly degraded. Ligation of methaemoglobin with N3-, which effectively b...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2008.140

    authors: Smalley JW,Birss AJ,Szmigielski B,Potempa J

    更新日期:2008-09-01 00:00:00

  • Bauhinia proteinase inhibitor-based synthetic fluorogenic substrates for enzymes isolated from insect midgut and caterpillar bristles.

    abstract::Bauhinia ungulata factor Xa inhibitor (BuXI) inactivates factor Xa and LOPAP, a prothrombin activator proteinase isolated from the venom of Lonomia obliqua caterpillar bristles. The reactive site of the enzyme-inhibitor interaction was explored to design specific substrates for both enzymes. Methionine is crucial for ...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2003.055

    authors: Andrade SA,Santomauro-Vaz EM,Lopes AR,Chudzinski-Tavassi AM,Juliano MA,Terra WR,Sampaio MU,Sampaio CA,Oliva ML

    更新日期:2003-03-01 00:00:00

  • The chemistry of nitrosative stress induced by nitric oxide and reactive nitrogen oxide species. Putting perspective on stressful biological situations.

    abstract::This review addresses many of the chemical aspects of nitrosative stress mediated by N2O3. From a cellular perspective, N2O3 and the resulting reactive nitrogen oxide species target specific motifs such as thiols, lysine active sites, and zinc fingers and is dependant upon both the rates of production as well as consu...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/BC.2004.001

    authors: Ridnour LA,Thomas DD,Mancardi D,Espey MG,Miranda KM,Paolocci N,Feelisch M,Fukuto J,Wink DA

    更新日期:2004-01-01 00:00:00

  • The structural biology of the amyloid precursor protein APP - a complex puzzle reveals its multi-domain architecture.

    abstract::The amyloid precursor protein (APP) and its processing are widely believed to be central for the etiology of Alzheimer's disease (AD) and appear essential for neuronal development and cell homeostasis in mammals. Many studies show the proteolysis of APP by the proteases α-, β- and γ-secretase, functional aspects of th...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/hsz-2013-0280

    authors: Coburger I,Hoefgen S,Than ME

    更新日期:2014-05-01 00:00:00

  • Structural features correlated with the extreme thermostability of 1[4Fe-4S] ferredoxin from the hyperthermophilic bacterium Thermotoga maritima.

    abstract::Understanding the molecular mechanisms behind extreme temperature stability is of relevance for the protein folding problem and for designing proteins for industrial and medical applications. A powerful approach for understanding the structural basis of thermostability is the comparison of high resolution structures o...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:

    authors: Macedo-Ribeiro S,Darimont B,Sterner R

    更新日期:1997-03-01 00:00:00

  • The activity and localization patterns of cathepsins B and X in cells of the mouse gastrointestinal tract differ along its length.

    abstract::Cysteine cathepsins are expressed in most tissues, including the gastrointestinal tract. We demonstrated an involvement of mouse intestinal cathepsin B in extracellular matrix remodeling for regeneration from trauma. The present study aimed at elucidating roles of cysteine cathepsins in the non-traumatized gastrointes...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/hsz-2014-0151

    authors: Tamhane T,Arampatzidou M,Gerganova V,Tacke M,Illukkumbura R,Dauth S,Schaschke N,Peters C,Reinheckel T,Brix K

    更新日期:2014-10-01 00:00:00

  • A structural network associated with the kallikrein-kinin and renin-angiotensin systems.

    abstract::The kallikrein-kinin and renin-angiotensin (KKS-RAS) systems represent two highly regulated proteolytic systems that are involved in several physiological and pathological processes. Although their protein-protein interactions can be studied using experimental approaches, it is difficult to differentiate between direc...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2010.046

    authors: Stoka V,Turk V

    更新日期:2010-04-01 00:00:00

  • Chaperone-assisted degradation: multiple paths to destruction.

    abstract::Molecular chaperones are well known as facilitators of protein folding and assembly. However, in recent years multiple chaperone-assisted degradation pathways have also emerged, including CAP (chaperone-assisted proteasomal degradation), CASA (chaperone-assisted selective autophagy), and CMA (chaperone-mediated autoph...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/BC.2010.058

    authors: Kettern N,Dreiseidler M,Tawo R,Höhfeld J

    更新日期:2010-05-01 00:00:00

  • The YidC/Oxa1/Alb3 protein family: common principles and distinct features.

    abstract::The members of the YidC/Oxa1/Alb3 protein family are evolutionary conserved in all three domains of life. They facilitate the insertion of membrane proteins into bacterial, mitochondrial, and thylakoid membranes and have been implicated in membrane protein folding and complex formation. The major classes of substrates...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/hsz-2012-0199

    authors: Saller MJ,Wu ZC,de Keyzer J,Driessen AJ

    更新日期:2012-11-01 00:00:00

  • Functional ribosome biogenesis is a prerequisite for p53 destabilization: impact of chemotherapy on nucleolar functions and RNA metabolism.

    abstract::The production and processing of ribosomal RNA is a complex and well-coordinated nucleolar process for ribosome biogenesis. Progress in understanding nucleolar structure and function has lead to the unexpected discovery of the nucleolus as a highly sensitive sensor of cellular stress and an important regulator of the ...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/hsz-2013-0153

    authors: Burger K,Eick D

    更新日期:2013-09-01 00:00:00

  • On the regulative role of the glutamate receptor in mitochondria.

    abstract::The purpose of this work was to study the regulative role of the glutamate receptor found earlier in the brain mitochondria. In the present work a glutamate-dependent signaling system with similar features was detected in mitochondria of the heart. The glutamate-dependent signaling system in the heart mitochondria was...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/hsz-2015-0289

    authors: Selin AA,Lobysheva NV,Nesterov SV,Skorobogatova YA,Byvshev IM,Pavlik LL,Mikheeva IB,Moshkov DA,Yaguzhinsky LS,Nartsissov YR

    更新日期:2016-05-01 00:00:00

  • The miRNA-kallikrein axis of interaction: a new dimension in the pathogenesis of prostate cancer.

    abstract::Kallikrein-related peptidases (KLKs) are a family of serine proteases that were shown to be useful cancer biomarkers. KLKs have been shown to be dysregulated in prostate cancer (PCa). microRNAs (miRNAs) are short RNA nucleotides that negatively regulate gene expression and have been reportedly dysregulated in PCa. We ...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/hsz-2011-0246

    authors: White NM,Youssef YM,Fendler A,Stephan C,Jung K,Yousef GM

    更新日期:2012-04-01 00:00:00

  • Cross talk between kinin and angiotensin II receptors in mouse abdominal aorta.

    abstract::Bradykinin (BK) is a vasorelaxant, algesic and inflammatory agent. Angiotensin II (AngII) is known to control vascular tone and promote growth, inflammation and artherogenesis. There is evidence for cross talking between BK and AngII receptors. Therefore, the effect of lack of kinin receptors was assessed in mice with...

    journal_title:Biological chemistry

    pub_type: 杂志文章

    doi:10.1515/BC.2009.081

    authors: Rodrigues ES,Martin RP,Felipe SA,Bader M,Oliveira SM,Shimuta SI

    更新日期:2009-09-01 00:00:00

  • How to get rid of mitochondria: crosstalk and regulation of multiple mitophagy pathways.

    abstract::Mitochondria are indispensable cellular organelles providing ATP and numerous other essential metabolites to ensure cell survival. Reactive oxygen species (ROS), which are formed as side reactions during oxidative phosphorylation or by external agents, induce molecular damage in mitochondrial proteins, lipids/membrane...

    journal_title:Biological chemistry

    pub_type: 杂志文章,评审

    doi:10.1515/hsz-2017-0206

    authors: Zimmermann M,Reichert AS

    更新日期:2017-12-20 00:00:00