Exp Neurobiol.  2013 Dec;22(4):315-321. 10.5607/en.2013.22.4.315.

Zinc-Triggered Induction of Tissue Plasminogen Activator and Plasminogen in Endothelial Cells and Pericytes

• Cho MK
• Sun ES
• Kim YH

• KMID: 2284635
• DOI: http://doi.org/10.5607/en.2013.22.4.315

Abstract

Cerebral amyloid angiopathy (CAA) is common in patients with Alzheimer's disease (AD) and may contribute to cerebral hemorrhage. We previously demonstrated that tissue plasminogen activator (tPA) and plasminogen (PLG) accumulated at the periphery of compact amyloid-cored plaques and in the walls of CAA-containing blood vessels in the brains of Tg2576 mice, a widely used AD mouse model. We had also observed that zinc-triggered tPA and PLG induction were observed in mouse cortical cultures. Because zinc also accumulates in amyloid plaques and blood vessel walls in AD brains, we examined whether zinc increases mRNA and protein levels of tPA and PLG in brain endothelial cells and pericytes. Four hours after the exposure of brain endothelial cells (bEnd.3) to 40 microM zinc, the mRNA and protein expressions of tPA and its substrate PLG were significantly increased. In the case of brain pericyte cultures, increases in tPA and PLG expression were also detected 2 hr after treatment. However, amyloid-beta (Abeta)1-42 oligomers did not augment tPA and PLG expression in bEnd.3 cells and pericytes, suggesting that zinc but not Abeta induces tPA and PLG accumulation in CAA found in the AD brain.

Keyword

zinc; amyloid-beta (Abeta); tissue plasminogen activator (tPA); plasminogen (PLG); cerebral amyloid angiopathy (CAA)

MeSH Terms

Alzheimer Disease
Animals
Blood Vessels
Brain
Cerebral Amyloid Angiopathy
Cerebral Hemorrhage
Endothelial Cells*
Humans
Mice
Pericytes*
Plaque, Amyloid
Plasminogen*
RNA, Messenger
Tissue Plasminogen Activator*
Zinc
Plasminogen
RNA, Messenger
Tissue Plasminogen Activator
Zinc