MassIVEapplication/xmlftp://massive-ftp.ucsd.edu/v02/MSV000083867/primaryOK2000000Andre Catichttps://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=6cb2fb2637a9441b94053f7593e9cb2cAndre.Catic@bcm.eduMassIVE21UNIMOD:1 - "Acetylation."UNIMOD:35 - "Oxidation or Hydroxylation."ProteomicsLTQ Orbitrap EliteQ ExactiveHomo Sapiens (ncbitaxon:9606)Baylor College of MedicineLoss of protein function is a driving force of ageing. We have identified peptidyl-prolyl isomerase A (PPIA or cyclophilin A) as a dominant chaperone in haematopoietic stem and progenitor cells. Depletion of PPIA accelerates stem cell ageing. We found that proteins with intrinsically disordered regions (IDRs) are frequent PPIA substrates. IDRs facilitate interactions with other proteins or nucleic acids and can trigger liquid-liquid phase separation. Over 20% of PPIA substrates are involved in the formation of supramolecular membrane-less organelles. PPIA affects regulators of stress granules (PABPC1), P-bodies (DDX6) and nucleoli (NPM1) to promote phase separation and increase cellular stress resistance. Haematopoietic stem cell ageing is associated with a post-transcriptional decrease in PPIA expression and reduced translation of IDR-rich proteins. Here we link the chaperone PPIA to the synthesis of intrinsically disordered proteins, which indicates that impaired protein interaction networks and macromolecular condensation may be potential determinants of haematopoietic stem cell ageing.The aim of the current study was to investigate the antioxidative effect of metformin (MTF) on bile duct ligation (BDL)-induced hepatic disorder and histological damage in rats. The rats were divided into 4 groups including sham control (SC), BDL alone (BDL surgery), MTF1 (BDL surgery and administration of 250 mg/kg of MFM) and MTF2 (BDL surgery and administration of 500 mg/kg of MTF). After BDL, the animals treated with MTF by gavage for 10 days. Hematoxylin and eosin staining, biochemical analysis and oxidative stress markers were assayed to determine histological alterations, liver functions, and oxidant/antioxidant status. Hepatotoxicity was verified by remarkable increase in plasma levels of aminotransferases and alkaline phosphatase activity and liver histology 10 days after the BDL surgery. Our finding showed that treatment with MTF markedly reduced plasma alkaline phosphatase and alleviated liver injury indices (<i>P</i> ≤ 0.05). Furthermore, BDL caused a considerable increase in the protein carbonyl and malondialdehyde content (<i>P</i> ≤ 0.05). However, MTF reduces oxidative stress by constraining the protein oxidation and lipid peroxidation, and increases antioxidant reserve by increasing the ferric reducing ability of plasma and reducing glutathione levels. MTF exerts antioxidative effects in the liver fibrosis and may represent a hepato-protective effect when given to rats with BDL-induced hepatic injury.Cyclophilin A supports translation of intrinsically disordered proteins and affects haematopoietic stem cell ageing.Metformin attenuates oxidative stress and liver damage after bile duct ligation in rats.Maneix Laure L, Iakova Polina P, Lee Charles G CG, Moree Shannon E SE, Lu Xuan X, Datar Gandhar K GK, Hill Cedric T CT, Spooner Eric E, King Jordon C K JCK, Sykes David B DB, Saez Borja B, Di Stefano Bruno B, Chen Xi X, Krause Daniela S DS, Sahin Ergun E, Tsai Francis T F FTF, Goodell Margaret A MA, Berk Bradford C BC, Scadden David T DT, Catic André ASadeghi Heibatollah H, Jahanbazi Fatemeh F, Sadeghi Hossein H, Omidifar Navid N, Alipoor Behnam B, Kokhdan Esmaeel Panahi EP, Mousavipoor Seyed Mehdi SM, Mousavi-Fard Seyed Hossein SH, Doustimotlagh Amir Hossein AHMother Cell, protein translation, Natively Unfolded, Unstructured, protein anabolism, PPIase A, Colony Forming Unit, Cyclophilin A, protein biosynthetic process, Unfolded Protein, Intrinsically, N-terminally processed, Peptidyl-Prolyl cis-trans Isomerase A, Natively, Moods, Unstructured Protein, Affects, Stem, Progenitor Cells, Colony-Forming Units, Progenitor Cell, Mother, stem cell, Peptidyl-prolyl cis-trans isomerase A, Rotamase A, Colony Forming Units, Mother., Natively Unfolded Protein, Disordered Protein, Cell, Intrinsically Disordered, animal stem cell, SP18, Colony-Forming Unit, protein synthesis, Stem Cell, Protein, Cells, protein formation, Mother Cells, Unstructured Proteins, protein biosynthesis, Natively Unfolded Proteins, Mood, 5.2.1.8, Progenitor, Intrinsically Disordered Protein, Cyclosporin A-binding proteincyph, MGC130048, gamma sarcoglycan, macromolecular complex, CypA, SGCG_HUMAN, cypa, DMDA1, 35 kDa dystrophin-associated glycoprotein, 2700098C05, protein complex, HEL-S-69p, protein containing complex, SG-gamma, Cell Lines, A4, macromolecule complex, protein, protein-containing complex, gamma (35kDa dystrophin-associated glycoprotein), TYPE, Cell, SGCG, LGMD2C, DAGA4, DMDA, 35kD dystrophin-associated glycoprotein, SCARMD2, 35DAG, Line, CYPH, gamma-sarcoglycan, Cphn, sarcoglycan, Cell., CYPA, CyP-18, protein aggregate, MAM, gamma-SG, SCG3, protein-protein complex, LinesPeptidyl Prolyl cis trans Isomerase, Rotamase, cyph, macromolecular complex, PPIase, CypA, Proline, cypa, 2700098C05, protein complex, Peptidyl-Prolyl cis-trans-Isomerase, HEL-S-69p, protein containing complex, macromolecule complex, protein, protein-containing complex, Proline Isomerase, Peptidylprolyl, cis-trans-Isomerase, Prolyl, protein-protein complex., Prolyl Isomerase, CYPH, Cphn, Peptidyl-Prolyl, CYPA, CyP-18, protein aggregate, Peptidylproline cis-trans-isomerase, Proline Rotamase, Isomeraseprotein translation, B23, HLR2, l(2)SH1908, protein, Organelle, anon-EST:Posey247, Disordered Protein, anon-EST:Posey249, Membrane Tissues, protein polypeptide chains, CG9063, Mother Cells, Scanning Transmission Electron Microscopy, protein aggregate, primary stem, Pabp, RCK, multicellular organismal biosynthetic process, single-organism biosynthetic process, l(2)k06607, pabp1, Intrinsically, anabolism, Moods, membrane region, Tissue, hypoplasia, Peptidyl-prolyl cis-trans isomerase A, proteins, rck, BcDNA:GH03694, high frequency, acidos nucleicos, mRCK|P54, Cphn, Natively Unfolded Proteins, Dhh1p/Me31b, DmelCG9063, CG5119, Intrinsically Disordered Protein, Membrane Tissue, AW546267, protein anabolism, DmRH3, Me31B, protein biosynthetic process, 2700098C05, Peptidyl-Prolyl cis-trans Isomerase A, l(2)SH2 1908, pAB, integral to membrane, Mat31B, Mother., PABP1, membranous organ component, PabpI, Electron Microscopy, Colony-Forming Unit, Stem Cell, nucleic acids, protein formation, E230023J21Rik, PABPC2, PABPC1, B23NP, cyph, Mother Cell, Acid, membrane of organ, CypA, cypa, NPM, Npm, DmelCG5119, pabpc2, Stem, pabpc1, BcDNAGH03694, Colony Forming Units, Natively Unfolded Protein, Granule, Nucleic, 3L6, loss of, animal stem cell, Npm1, primary axis, protein synthesis, rich, BcDNA:LD24412, Cells, P54, STEM, CYPH, Unstructured Proteins, Acids, CYPA, AU042049, p54h, p54, Colony-Forming Units, Progenitor Cell, Gene, stalk, biosynthesis, protein-containing complex, RGD1564560, Intrinsically Disordered, connexin43, acides nucleiques, polypeptide chain, reduced, integral component of membrane, DmelCG4916, resistance, Gene Products, Mood, tiny, Progenitor, DDX6, Natively Unfolded, PPIase A, Unfolded Protein, formation, Tissues, ME31B, Mother, culm, synthesis, SP18, Pabp1, Me31b, Cnx43, region of membrane, liquid, CyP-18, small, membrane, Unstructured, Colony Forming Unit, Stress Granule, protein complex, axis, acide nucleique, Phase Separations, synthesize, Affects, Unstructured Protein, HEL-S-69p, Progenitor Cells, Proteins, PABPL1, Rotamase A, function, Scanning Transmission, CG4916, Cell, mRCK/P54, native protein, natural protein, Nucleic Acid, Pabpl1, Protein, whole membrane, protein biosynthesis, NA, Isomerase, NO38, Separation, Phase, ePAB, transmembrane, PAB1, l(2)k10109, dPABP, Cyclophilin A, frequent, Nukleinsaeure, underdeveloped, N-terminally processed, pabp, 1110001P04Rik, Natively, Separations, stem cell, acido nucleico, Membrane, PABP, PAbp, Protein Gene Products, Gene Proteins, PABP55B, pABP, Nukleinsaeuren, Stress, Cx43alpha1, pab1, Cx43, Gja-1, 5.2.1.8, Cyclosporin A-binding protein, duo0PXD014025falsePeptidylprolyl isomerase A (PPIA) protein complexIdentification of PPIA protein complex using wild type and mutant cell lines.Mon May 27 21:22:00 BST 2019MSV00008386738553595