Biogerontology

, Volume 7, Issue 5, pp 375–382

Clusterin/Apolipoprotein J up-regulation after zinc exposure, replicative senescence or differentiation of human haematopoietic cells

Authors

  • Ioannis P. Trougakos
    • Laboratory of Molecular & Cellular Ageing, Institute of Biological Research & BiotechnologyNational Hellenic Research Foundation
  • Graham Pawelec
    • Center for Medical Research (ZMF)University of Tübingen
  • Christos Tzavelas
    • Laboratory of Molecular & Cellular Ageing, Institute of Biological Research & BiotechnologyNational Hellenic Research Foundation
  • Triantaphillia Ntouroupi
    • Laboratory of Molecular & Cellular Ageing, Institute of Biological Research & BiotechnologyNational Hellenic Research Foundation
    • Laboratory of Molecular & Cellular Ageing, Institute of Biological Research & BiotechnologyNational Hellenic Research Foundation
Research Article

DOI: 10.1007/s10522-006-9052-8

Cite this article as:
Trougakos, I.P., Pawelec, G., Tzavelas, C. et al. Biogerontology (2006) 7: 375. doi:10.1007/s10522-006-9052-8

Abstract

Clusterin/Apolipoprotein J (CLU) is a cellular senescence biomarker implicated in several physiological processes. In this work we have investigated CLU expression and function in human haematopoietic cells. We found that early passage human T cell clones (TCC) express minimal endogenous amounts of CLU, which are significantly elevated in late passage cells. Moreover, exposure of TCC to increased levels of the essential micronutrient zinc in culture resulted in intense induction of CLU. Because haematopoietic cells cease proliferation following induction of terminal differentiation, we also studied the expression profile of CLU in the leukemic progenitor cell lines K562 and HL-60. We found that, like TCC, both cell lines express minimal endogenous levels of CLU in their actively proliferating state. However, when induced to differentiate into their distinct cell types, CLU was found to be up-regulated specifically in those cells expressing the main differentiation markers. Enforced stable over-expression of CLU in K562 cells inhibited the expression of the CD14 differentiation marker and blocked differentiation to either monocytes/megacaryoblasts or to erythrocytes. Overall, our results suggest that CLU is actively involved in both replicative senescence and terminal differentiation in different types of human haematopoietic cells.

Keywords

Clusterin/Apolipoprotein JDifferentiationHaematopoietic cell linesMonoclonal human T lymphocytesSenescenceZinc

Abbreviations

CLU

clusterin/apolipoprotein J

TCC

T cell clones

VSMC

vascular smooth muscle cell

PMA

12-phorbol-myristate acetate

DMSO

dimethyl sulfoxide

cCLU

intracellular clusterin/apolipoprotein J precursor

sCLU

secreted clusterin/apolipoprotein J isoform

PDs

population doublings

Copyright information

© Springer Science+Business Media B.V. 2006