Matteo Strano Università di Cassino, Dip. Ingegneria Industriale Cassino (FR), Italy
MECHANISMS RESPONSIBLE FOR BETA-AMYLOID-DEPENDENT REDUCTION OF ERYTHROCYTE DEFORMABILITY Francesco...
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Transcript of MECHANISMS RESPONSIBLE FOR BETA-AMYLOID-DEPENDENT REDUCTION OF ERYTHROCYTE DEFORMABILITY Francesco...
MECHANISMS RESPONSIBLE FOR BETA-AMYLOID-DEPENDENT
REDUCTION OF ERYTHROCYTE DEFORMABILITY
Francesco MisitiUniversity of Cassino and Southern Lazio
Cassino (Italy)
o A are associated with cerebral blood vessels
o A are transferred to blood
o A are produced by platelets
o Blood cells are exposed to A(1-42) and (1-40)
o Erythrocytes interact with A(1-42)
o A alters erythrocyte shape and deformability
o A impairs oxygen delivery to brain
Erythrocytes and Alzheimer
Objective
o Nitric Oxide: a regulatory factor of erythrocyte mechanical properties
o Nitric Oxide synthase (eNOS) is expressed in erythrocyteso PKC andCaspase 3responsible for regulation on eNOS
function o Pentose Phosphate Pathway (PPP): responsible for
erythrocyte antioxidant defense
Clarify the role played by Nitric Oxide synthase (eNOS) signaling pathway in the A-dependent alteration of erythrocyte morphology
Control
Amyloid
Immuno-histochemical staining of erythrocyte activated nitric oxide synthase (eNOS)
* P< 0.05 vs. control;
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.
* P < 0.05 vs. control; # P < 0.05 vs. Aβ at 24 hours.
Time course of the effects of Aβ on nitrite and nitrate levels in erythrocytes
suspensions
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.
Misiti et al. Biochem Cell Biol.86: 1-8 (2008) Mandal et al. JBC 278: 52551-52558 (2003)
Band 3 degradation by Caspase 3
Ctr A A
Ctr A
--32kDa
--20 kDa
Reduction in antioxidant defense (Pentose Phosphate Pathway)
Clementi et al. Int. J. Biochem Cell Biol., 36(10):2066-76 (2004)
Ctr A
** P < 0.05 vs. A at 24 hours
Misiti et al. Biochem Cell Biol.86: 1-8 (2008)
A dependent reduced stimulus for endogenous NO synthesis in the vasculature
Ctr A
Conclusions
A/erythrocyte interaction induces :
o an imbalance in the antioxidant defense (PPP flux reduction)
o Caspase 3 activationo PKCactivation o eNOS down-regulationo NO levels reduction
Conclusions
A/erythrocyte interaction induces :
o an imbalance in the antioxidant defense (PPP flux reduction)
o Caspase 3 activationo PKCactivation o eNOS down-regulationo NO levels reduction
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 SampaoleseMarco Girasole
: