• KSBNS 2024


Original Article

Exp Neurobiol 2013; 22(4): 315-321

Published online December 30, 2013

© The Korean Society for Brain and Neural Sciences

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

Mun-Kyung Cho, Eun-Sun Sun and Yang-Hee Kim*

Department of Molecular Biology, Sejong University, Seoul 143-747, Korea

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-2-3408-3648, FAX: 82-2-3408-4336

Received: November 18, 2013; Revised: December 20, 2013; Accepted: December 23, 2013


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 µM 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-β (Aβ)1-42 oligomers did not augment tPA and PLG expression in bEnd.3 cells and pericytes, suggesting that zinc but not Aβ induces tPA and PLG accumulation in CAA found in the AD brain.

Keywords: zinc, amyloid-β (Aβ), tissue plasminogen activator (tPA), plasminogen (PLG), cerebral amyloid angiopathy (CAA)