title: Proteasome subunits mRNA expressions correlate with male BMI: implications for a role in obesity.
abstract: Obesity as well as its associated chronic diseases and adverse health consequences such as type 2 diabetes mellitus, dyslipidemia, hypertension, and coronary artery disease are afflicting middle-aged adults and an ever greater number of children globally. We planned to investigate new obesity-related factors using proteomics approaches in a randomly selected three high and three low BMI samples of Epstein-Barr-transformed B (EBV-B) lymphoblastoid cell lines prepared from two groups of young Japanese men with different BMI. To search novel obesity-related factors, comparisons of protein expressions between high and low BMI groups were carried out by two-dimensional gel electrophoresis (2-DE). Gene transcripts of proteasome subunits found out from 2-DE were further determined by quantitative real-time PCR. Results from proteomics approach showed that the expression of proteasome alpha subunit type 5 (PSMA5) was significantly lower in the high BMI male group than in those with low BMI (P < 0.05). To validate these results, we expanded the study to include 20 more men and used real-time PCR to quantify the mRNA expression level in their EBV-B cells. Both PSMA5 and PSMA2 of EBV-B cells showed negative correlation with BMI. Furthermore, the mRNA levels measured in the peripheral blood B lymphocytes for many proteasome subunits in 75 healthy men and women showed significant negative correlation with BMI in healthy men. Our findings suggest that proteasome expression may play a key role in obesity.
authors.affiliation: Department of Human Genetics and Public Health, Faculty of Medicine, Graduate School of Proteomics, The University of Tokushima, Tokushima, Japan.
authors.forename: Kozue
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Youichi
authors.initials: Y
authors.lastname: Sato
authors.forename: Toshikatsu
authors.initials: T
authors.lastname: Shinka
authors.forename: Masako
authors.initials: M
authors.lastname: Sei
authors.forename: Isoko
authors.initials: I
authors.lastname: Nomura
authors.forename: Mayumi
authors.initials: M
authors.lastname: Umeno
authors.forename: Ashraf A
authors.initials: AA
authors.lastname: Ewis
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakahori
mesh_terms: D015992:Body Mass Index; D002460:Cell Line; D017931:DNA Primers; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D008297:Male; D009765:Obesity / Q000235:genetics*; D016133:Polymerase Chain Reaction; D046988:Proteasome Endopeptidase Complex / Q000097:blood / Q000235:genetics*; D021122:Protein Subunits / Q000097:blood / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D012016:Reference Values; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D017931:DNA Primers; D021122:Protein Subunits; D012333:RNA, Messenger; D046988:Proteasome Endopeptidase Complex