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Conflict of Interest

MECHANISMS RESPONSIBLE FOR BETA-AMYLOID-DEPENDENT REDUCTION OF ERYTHROCYTE DEFORMABILITY Francesco Misiti University of Cassino and Southern Lazio Cassino (Italy). Conflict of Interest. Francesco Misiti Has no real or apparent conflicts of interest to report. Erythrocytes and Alzheimer.

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Conflict of Interest

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  1. MECHANISMS RESPONSIBLE FOR BETA-AMYLOID-DEPENDENT REDUCTION OF ERYTHROCYTE DEFORMABILITYFrancesco MisitiUniversity of Cassino and Southern LazioCassino (Italy)

  2. Conflict of Interest • Francesco Misiti • Has no real or apparent conflicts of interest to report

  3. Erythrocytes and Alzheimer • Ab are associatedwithcerebralbloodvessels • Ab are transferredtoblood • Ab are producedbyplatelets • Bloodcells are exposedtoAb(1-42) and (1-40) • ErythrocytesinteractwithAb(1-42) • Abalterserythrocyteshape and deformability • Abimpairsoxygen delivery tobrain

  4. Effects of Aβ on erythrocyte morphology Amyloid Control

  5. Membrane AChE activity as a marker of membrane integrity * P < 0.05 vs. control

  6. Objective Clarify the roleplayedbyNitricOxidesynthase (eNOS) signalingpathway in the Ab-dependentalterationoferythrocytemorphology • NitricOxide: a regulatory factor of erythrocyte mechanical properties • NitricOxidesynthase (eNOS) isexpressed in erythrocytes • PKC a andCaspase 3:responsible for regulation on eNOS function • PentosePhosphatePathway (PPP):responsibleforerythrocyteantioxidantdefense

  7. Western blot analysis showing the conformational species of Ab Piacentini et al. J Neurochem (2008)

  8. Western blot analysis showing the conformational species of Ab Piacentini et al. J Neurochem (2008)

  9. Immuno-histochemical staining of erythrocyte activated nitric oxide synthase (eNOS) Control Amyloid * P< 0.05 vs. control;

  10. Time course of the effects of Aβ on nitrite and nitrate levels in erythrocytes suspensions * P < 0.05 vs. control; # P < 0.05 vs.Aβ at 24 hours.

  11. Time course of the effects of Aβ on nitrite and nitrate levels in erythrocytes suspensions * P < 0.05 vs. control; # P < 0.05 vs.Aβ at 24 hours.

  12. AChE inhibitors abrogate the effects of Aβ on nitrite and nitrate levels in erythrocytes suspensions * P < 0.05 vs. control; # P < 0.05 vs.Aβ at 24 hours.

  13. PKCaactivationbyAb cytosol (80 kDa) PKCa (80 kDa)PKCa membrane Ctr Ab + PMA + PMA amyloid control

  14. PKCaactivationbyAb cytosol (80 kDa) PKCa (80 kDa)PKCa membrane Ctr Ab + PMA + PMA amyloid control

  15. Caspase 3 activationbyAb : activity Clementi et al. Int J Biochem Cell Biol. 39: 727-735 (2007)

  16. Caspase 3 activation by Ab: WB --32kDa --20 kDa Ctr Ab Misiti et al. Biochem Cell Biol.86: 1-8 (2008)

  17. Band 3 degradation by Caspase 3 --32kDa --20 kDa Ctr Ab CtrAbAb Misiti et al. Biochem Cell Biol.86: 1-8 (2008) Mandal et al. JBC 278: 52551-52558 (2003)

  18. Reduction in antioxidant defense (Pentose Phosphate Pathway) CtrAb Clementi et al. Int. J. Biochem Cell Biol., 36(10):2066-76 (2004) ** P < 0.05 vs.Ab at 24 hours

  19. Ab dependent reduced stimulus for endogenous NO synthesis in the vasculature CtrAb Misiti et al. Biochem Cell Biol.86: 1-8 (2008)

  20. Conclusions Ab/erythrocyteinteractioninduces : • animbalance in the antioxidantdefense (PPP fluxreduction) • Caspase 3 activation • PKCaactivation • eNOSdown-regulation • NO levelsreduction

  21. Conclusions Ab/erythrocyteinteractioninduces : • animbalance in the antioxidantdefense (PPP fluxreduction) • Caspase 3 activation • PKCaactivation • eNOSdown-regulation • NO levelsreduction

  22. Acknowledgements University of Cassino and Southern Lazio- Cassino Cristiana Carelli Alinovi Catholic University-School of Medicine- Rome Bruno Giardina Research National Council (CNR)-ICRM & ISM Beatrice Sampaolese Marco Girasole :

  23. UNIVERSITY OF CASSINO AND SOUTHERN LAZIO

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