Apolipoprotein J/clusterin in human erythrocytes is involved in the molecular process of defected material disposal during vesiculation.
BACKGROUND
We have showed that secretory Apolipoprotein J/Clusterin (sCLU) is down-regulated in senescent, stressed or diseased red blood cells (RBCs). It was hypothesized that sCLU loss relates to RBCs vesiculation, a mechanism that removes erythrocyte membrane patches containing defective or potentially harmful components.


RESULTS
To investigate this issue we employed a combination of biochemical and microscopical approaches in freshly prepared RBCs or RBCs stored under standard blood bank conditions, an in vitro model system of cellular aging. We found that sCLU is effectively exocytosed in vivo during membrane vesiculation of freshly prepared RBCs. In support, the RBCs' sCLU content was progressively reduced during RBCs ex vivo maturation and senescence under cold storage due to its selective exocytosis in membrane vesicles. A range of typical vesicular components, also involved in RBCs senescence, like Band 3, CD59, hemoglobin and carbonylated membrane proteins were found to physically interact with sCLU.


CONCLUSIONS
The maturation of RBCs is associated with a progressive loss of sCLU. We propose that sCLU is functionally involved in the disposal of oxidized/defected material through RBCs vesiculation. This process most probably takes place through sCLU interaction with RBCs membrane proteins that are implicit vesicular components. Therefore, sCLU represents a pro-survival factor acting for the postponement of the untimely clearance of RBCs.
Department of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Panepistimiopolis, Athens, Greece.
Marianna H
MH
Antonelou
Anastasios G
AG
Kriebardis
Konstantinos E
KE
Stamoulis
Ioannis P
IP
Trougakos
Issidora S
IS
Papassideri
D000328:Adult; D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism; D018957:CD59 Antigens / Q000378:metabolism; D016922:Cellular Senescence; D051152:Clusterin / Q000378:metabolism*; D004910:Erythrocyte Membrane / Q000378:metabolism*; D005089:Exocytosis; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D010084:Oxidation-Reduction; D013312:Stress, Physiological
D001457:Anion Exchange Protein 1, Erythrocyte; D018957:CD59 Antigens; D051152:Clusterin; D006454:Hemoglobins