Exp Neurobiol.  2009 Jun;18(1):48-56. 10.5607/en.2009.18.1.48.

Regulation of the Activity of Tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 by Zinc in Rat Primary Astrocytes

• Lee SY
• Kim HJ
• Joo SH
• Kwon KJ
• Lee J
• Han SH
• Cho JY
• Cheong JH
• Ko KH
• Shin CY

• KMID: 2165296
• DOI: http://doi.org/10.5607/en.2009.18.1.48

Abstract

Tissue-type plasminogen activator (tPA) is a serine proteinase which plays important roles in functional and structural synaptic plasticity, neural migration, as well as excitotoxic injuries in several pathological situations including ischemic stroke, seizure and Alzheimer's disease (AD). It has been suggested that a divalent cation zinc also plays pathological roles in ischemia and seizure. Interestingly, it has been suggested that zinc and tPA may negatively regulate the activity or the level of each other by mechanism involving physical interaction between the two. In the present study, we investigated the effect of zinc in tPA activity and expression in rat primary astrocyte. Astrocytes were transiently exposed to 20~200micrometer Zn2+ for 2 h and then were recovered for 24 h. In the culture supernatants, zinc treatment concentration-dependently inhibited the activity of tPA which was determined by casein-plasminogen zymography. There was only marginal changes, if any, in the level of tPA mRNA and protein. On the other hand, the activity of an endogenous inhibitor of tPA, plasminogen activator inhibitor-1 (PAI-1) as well as its expression was increased by zinc treatment in a concentration-dependant manner. These results suggest that zinc-induced decrease in tPA activity was also, at least in part, regulated by indirect way by regulating the level of PAI-1. The decrease in tPA activity may be a part of body's plan to reduce excitotoxic neural injury in a condition of elevated zinc in the brain.

Keyword

tissue-type plasminogen activator (tPA); zinc; plasminogen activator inhibitor (PAI)-1; neuronal damage; astrocyte

MeSH Terms

Alzheimer Disease
Animals
Astrocytes
Brain
Hand
Ischemia
Plasminogen
Plasminogen Activator Inhibitor 1
Plasminogen Activators
Plastics
Rats
RNA, Messenger
Seizures
Serine Proteases
Stroke
Tissue Plasminogen Activator
Zinc
Plasminogen
Plasminogen Activator Inhibitor 1
Plasminogen Activators
Plastics
RNA, Messenger
Serine Proteases
Tissue Plasminogen Activator
Zinc