title: Over expression of proteins that alter the intracellular signaling pathways in the cytoplasm of the liver cells forming Mallory-Denk bodies.
abstract: In this study, liver biopsy sections fixed in formalin and embedded in paraffin (FFPE) from patients with alcoholic hepatitis (AH) were used. The results showed that the expression of the SYK protein was up regulated by RNA-seq and real time PCR analyses in the alcoholic hepatitis patients compared to controls. The results were supported by using the IHC fluorescent antibody staining intensity morphometric quantitation. Morphometric quantification of fluorescent intensity measurement showed a two fold increase in SYK protein in the cytoplasm of the cells forming MDBs compared to surrounding normal hepatocytes. The expression of AKT1 was also analyzed. AKT1 is a serine/threonine-specific protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription and cell migration. The AKT protein was also increased in hepatocyte balloon cells forming MDBs. This observation demonstrates the role of SYK and its subsequent effect on the internal signaling pathways such as PI3K/AKT as well as p70S6K, as a potential multifunctional target in protein quality control mechanisms of hepatocytes when ER stress is activated.
authors.affiliation: Department of Pathology, Harbor UCLA Medical Center and Los Angeles BioMedical Institute, 1000W, Carson, Torrance, CA 90509, United States.
authors.forename: N
authors.initials: N
authors.lastname: Afifiyan
authors.affiliation: Department of Pathology, Harbor UCLA Medical Center and Los Angeles BioMedical Institute, 1000W, Carson, Torrance, CA 90509, United States.
authors.forename: B
authors.initials: B
authors.lastname: Tillman
authors.affiliation: Department of Pathology, Harbor UCLA Medical Center and Los Angeles BioMedical Institute, 1000W, Carson, Torrance, CA 90509, United States.
authors.forename: B A
authors.initials: BA
authors.lastname: French
authors.affiliation: Department of Pathology, Harbor UCLA Medical Center and Los Angeles BioMedical Institute, 1000W, Carson, Torrance, CA 90509, United States.
authors.forename: M
authors.initials: M
authors.lastname: Masouminia
authors.affiliation: Department of Pathology, Harbor UCLA Medical Center and Los Angeles BioMedical Institute, 1000W, Carson, Torrance, CA 90509, United States.
authors.forename: S
authors.initials: S
authors.lastname: Samadzadeh
authors.affiliation: Department of Pathology, Harbor UCLA Medical Center and Los Angeles BioMedical Institute, 1000W, Carson, Torrance, CA 90509, United States. Electronic address: sfrench@labiomed.org.
authors.forename: S W
authors.initials: SW
authors.lastname: French
mesh_terms: D001706:Biopsy; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism*; D006519:Hepatitis, Alcoholic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D059609:Mallory Bodies / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000072377:Syk Kinase / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D019869:Phosphatidylinositol 3-Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa
keywords: AKT1; Alcoholic hepatitis; Mallory-Denk bodies; SYK