title: Elevation of serum fortilin levels is specific for apoptosis and signifies cell death in vivo.
abstract: BACKGROUND
  Billions of cells undergo apoptosis each day in the average normal adult. The ability to readily assess the degree of apoptosis in human diseases is hampered by the lack of sensitive and specific serum biomarkers of apoptosis. Fortilin is a novel prosurvival molecule that protects cells against various noxious stimuli. While fortilin is secreted into the extracellular space under certain conditions, the relationship between the serum concentration of fortilin and the presence and extent of apoptosis in vivo remains unknown.
  
  
  RESULTS
  Using a newly developed fortilin ELISA system, we show here that fortilin exists in the normal human and mouse circulation. We further demonstrate that fortilin serum levels are significantly elevated in patients with solid cancer, in response to anti-cancer chemo- or radiation therapy. The elevation of fortilin serum levels is more robust and sensitive than that of such previously-reported serum biomarkers of apoptosis as fragmented cytokeratin-18, cytochrome c, and nucleosomal DNA. In addition, targeted apoptotic liver damage induced by Jo2 anti-Fas (CD95) antibody consistently and significantly increased serum fortilin levels in C57BL/6J mice. Finally, when challenged by anti-human-Fas IgM antibody, Jurkat leukemic T cells apoptosed and released fortilin into the medium before plasma membrane integrity was compromised.
  
  
  CONCLUSIONS
  Taken together, these data suggest that serum fortilin levels reflect the degree and extent of apoptosis occurring in vivo.
  
  
  CONCLUSIONS
  Fortilin is a viable serum biomarker of in vivo apoptosis and can be utilized to noninvasively assess the status of in vivo apoptosis in humans.
authors.affiliation: Division of Cardiology, University of Texas Medical Branch at Galveston, TX 77555, USA ; Center for Genomics and Bioinformatics Research, Faculty of Science, Prince of Songkla University, Thailand.
authors.forename: Patuma
authors.initials: P
authors.lastname: Sinthujaroen
authors.affiliation: Division of Cardiology, University of Texas Medical Branch at Galveston, TX 77555, USA.
authors.forename: Nattaporn
authors.initials: N
authors.lastname: Wanachottrakul
authors.affiliation: Division of Cardiology, University of Texas Medical Branch at Galveston, TX 77555, USA.
authors.forename: Decha
authors.initials: D
authors.lastname: Pinkaew
authors.affiliation: Department of Pathology, University of Texas Medical Branch at Galveston, TX 77555, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Petersen
authors.affiliation: Center for Genomics and Bioinformatics Research, Faculty of Science, Prince of Songkla University, Thailand.
authors.forename: Amornrat
authors.initials: A
authors.lastname: Phongdara
authors.affiliation: Division of Endocrinology and Metabolism within the Department of Internal Medicine, University of Texas Medical Branch at Galveston, TX 77555, USA.
authors.forename: Melinda
authors.initials: M
authors.lastname: Sheffield-Moore
authors.affiliation: Division of Cardiology, University of Texas Medical Branch at Galveston, TX 77555, USA ; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, TX 77555, USA.
authors.forename: Ken
authors.initials: K
authors.lastname: Fujise
keywords: Apoptosis; Biomarker; Fortilin; Programmed Cell Death