Human serum albumin and its N-terminal tetrapeptide (DAHK) block oxidant-induced neuronal death.

Abstract:

BACKGROUND AND PURPOSE:Studies using animal models of stroke have shown that human serum albumin (HSA) significantly ameliorates cerebral ischemic injury after both transient and permanent ischemia, even when administered after the onset of ischemia or reperfusion. The mechanism of this effect remains uncertain, and prior studies suggest both indirect hemodynamic and direct cytoprotective effects. HSA is a potent antioxidant, in part because of its strong copper-binding capacity. Here we examined the effect of HSA on oxidant-induced neuronal death in a cortical cell culture system. METHODS:Murine cortical cultures were exposed to oxidative stress generated by hydrogen peroxide and by a mixture of copper plus ascorbic acid. We examined the ability of HSA and a tetrapeptide occupying its N-terminus (DAHK) to prevent neuronal death after these challenges. RESULTS:H(2)O(2) and CuCl(2)/ascorbic acid were used at concentrations that, in the absence of HSA, killed >90% of the neurons. HSA provided complete protection at a concentration of 37.5 micromol/L and 50% protection at 3.75 micromol/L. The copper-binding tetrapeptide DAHK had nearly identical potency and efficacy. HSA and DAHK were also equally effective in preventing neuronal death induced by CuCl(2)/ascorbic acid. CONCLUSIONS:HSA has potent antioxidant properties, probably due to binding of copper and other transition metals. HSA extravasation into ischemic brain may provide neuroprotection by limiting metal-catalyzed oxidant stress. The tetrapeptide DAHK may be an effective, small-molecular-weight alternative to HSA as a therapeutic agent for stroke.

journal_name

Stroke

journal_title

Stroke

authors

Gum ET,Swanson RA,Alano C,Liu J,Hong S,Weinstein PR,Panter SS

doi

10.1161/01.STR.0000110790.05859.DA

subject

Has Abstract

pub_date

2004-02-01 00:00:00

pages

590-5

issue

2

eissn

0039-2499

issn

1524-4628

pii

01.STR.0000110790.05859.DA

journal_volume

35

pub_type

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