title: Analysis of Alpha-2 Macroglobulin from the Long-Lived and Cancer-Resistant Naked Mole-Rat and Human Plasma.
abstract: BACKGROUND
  The naked mole-rat (NMR) is a long-lived and cancer resistant species. Identification of potential anti-cancer and age related mechanisms is of great interest and makes this species eminent to investigate anti-cancer strategies and understand aging mechanisms. Since it is known that the NMR expresses higher liver mRNA-levels of alpha 2-macroglobulin than mice, nothing is known about its structure, functionality or expression level in the NMR compared to the human A2M.
  
  
  RESULTS
  Here we show a comprehensive analysis of NMR- and human plasma-A2M, showing a different prediction in glycosylation of NMR-A2M, which results in a higher molecular weight compared to human A2M. Additionally, we found a higher concentration of A2M (8.3±0.44 mg/mL vs. and 4.4±0.20 mg/mL) and a lower total plasma protein content (38.7±1.79 mg/mL vs. 61.7±3.20 mg/mL) in NMR compared to human. NMR-A2M can be transformed by methylamine and trypsin resulting in a conformational change similar to human A2M. NMR-A2M is detectable by a polyclonal antibody against human A2M. Determination of tryptic and anti-tryptic activity of NMR and human plasma revealed a higher anti-tryptic activity of the NMR plasma. On the other hand, less proteolytic activity was found in NMR plasma compared to human plasma.
  
  
  CONCLUSIONS
  We found transformed NMR-A2M binding to its specific receptor LRP1. We could demonstrate lower protein expression of LRP1 in the NMR liver tissue compared to human but higher expression of A2M. This was accompanied by a higher EpCAM protein expression as central adhesion molecule in cancer progression. NMR-plasma was capable to increase the adhesion in human fibroblast in vitro most probably by increasing CD29 protein expression. This is the first report, demonstrating similarities as well as distinct differences between A2M in NMR and human plasma. This might be directly linked to the intriguing phenotype of the NMR and suggests that A2M might probably play an important role in anti-cancer and the anti-aging mechanisms in the NMR.
authors.affiliation: Institute of Biochemistry, University of Leipzig, Leipzig, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Thieme
authors.affiliation: Institute of Biochemistry, University of Leipzig, Leipzig, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Kurz
authors.affiliation: Institute of Biochemistry, University of Leipzig, Leipzig, Germany.
authors.forename: Marlen
authors.initials: M
authors.lastname: Kolb
authors.affiliation: Institute of Biochemistry, University of Leipzig, Leipzig, Germany.
authors.forename: Tewodros
authors.initials: T
authors.lastname: Debebe
authors.affiliation: Department of Reproduction Management, Leibniz Institute for Zoo and Wildlife Research, Berlin, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Holtze
authors.affiliation: Department of Reproduction Management, Leibniz Institute for Zoo and Wildlife Research, Berlin, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Morhart
authors.affiliation: Fritz Lipmann Institute-Leibniz Institute for Age Research, Jena, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Huse
authors.affiliation: Fritz Lipmann Institute-Leibniz Institute for Age Research, Jena, Germany.
authors.forename: Karol
authors.initials: K
authors.lastname: Szafranski
authors.affiliation: Fritz Lipmann Institute-Leibniz Institute for Age Research, Jena, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Platzer
authors.affiliation: Department of Reproduction Management, Leibniz Institute for Zoo and Wildlife Research, Berlin, Germany.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Hildebrandt
authors.affiliation: Institute of Biochemistry, University of Leipzig, Leipzig, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Birkenmeier
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D006801:Humans; D019577:Mole Rats; D009369:Neoplasms / Q000097:blood*; D010802:Phylogeny; D000511:alpha-Macroglobulins / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D000511:alpha-Macroglobulins