title: Modulation of AP-endonuclease1 levels associated with hepatic cirrhosis in rat model treated with human umbilical cord blood mononuclear stem cells.
abstract: Oxidative stress in liver cells may contribute to the etiology of hepatic diseases, as in liver cirrhosis. AP-Endonuclease1 (APE1/Ref-1) is essential for cell protection toward oxidative stress by acting as a transcriptional regulator of pro-survival genes and as a redox sensitive protein. The aim of this study was to critically analyze the various parameters governing the success of human umbilical cord blood mononuclear stem cell-based (MNCs) therapy without the use of an immunosuppressant and to investigate for the first time the expression of APE1 during thioacetamide (TAA)-induced cirrhosis and MNCs therapy in a rat model. Umbilical cord blood samples from full-term deliveries were collected. Lethal fulminant hepatic cirrhosis in rats was induced by intraperitoneal injection of thio-acetamide. MNCs were then intrahepatically transplanted. We measured APE1 expression at mRNA and protein levels, mRNA expression of TGF-β, α-SMA, STAP, CTGF, MMP-9 and TIMP-1 in a follow up study. Histopathological and immunohistochemical analyses were performed 10 weeks after intrahepatic injection of the cells. Transdifferentiated cells could be efficiently stained with antihuman hepatocytes. Interestingly, human hepatocyte-specific markers, human albumin, cytokeratin-18 and cytokeratin-19 mRNAs were detected in rat liver after 10 days of MNCs infusion. MNC transplanted by intrahepatic route, could engraft recipient liver, differentiated into functional hepatocytes, and rescued liver failure. Moreover up regulation of APE1 expression confirmed by marked immunohistochemical staining may be involved in MNCs-induced hepatocytes regeneration suggesting that maintaining high level of APE1 has protective effect as pro-survival signal.
authors.affiliation: Department of Biochemistry, Alexandria University, Egypt. arbassiouny@yahoo.com
authors.forename: Ahmad R
authors.initials: AR
authors.lastname: Bassiouny
authors.forename: Amira Z
authors.initials: AZ
authors.lastname: Zaky
authors.forename: Shaymaa A
authors.initials: SA
authors.lastname: Abdulmalek
authors.forename: Kamal M
authors.initials: KM
authors.lastname: Kandeel
authors.forename: Alaa
authors.initials: A
authors.lastname: Ismail
authors.forename: Marie
authors.initials: M
authors.lastname: Moftah
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D055513:Connective Tissue Growth Factor / Q000235:genetics; D036101:Cord Blood Stem Cell Transplantation; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D053538:Keratin-18 / Q000235:genetics; D053539:Keratin-19 / Q000235:genetics; D015227:Lipid Peroxidation; D008099:Liver / Q000201:enzymology / Q000473:pathology / Q000601:surgery*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D008115:Liver Regeneration; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071456:Sequestosome-1 Protein; D012709:Serum Albumin / Q000235:genetics; D013853:Thioacetamide; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics
chemical_list: D000199:Actins; D055513:Connective Tissue Growth Factor; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D006360:Heat-Shock Proteins; D053538:Keratin-18; D053539:Keratin-19; D020780:Matrix Metalloproteinase 9; D012333:RNA, Messenger; D000071456:Sequestosome-1 Protein; D012709:Serum Albumin; D013853:Thioacetamide; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; C526316:CCN2 protein, rat; C488421:KRT18 protein, human; C491079:Sqstm1 protein, rat; C498862:Acta2 protein, rat; C470319:Apex1 protein, rat
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