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KMID : 0614020050200010082
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Journal of Pharmaceutical Sciences (C.N.U.)
2005 Volume.20 No. 1 p.82 ~ p.89
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Protective Action of N-terminal Sequence (DAHK)of Human Serum Albumin Against Lipoprotein Oxidation
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Nguyen Duy-Su
Wei Chun-hua
Jeong Tae-Sook
Sok Dai-Eun
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Abstract
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N-terminal four amino acid peptide of human serum albumin (DANK) is observed to exhibit antioxidant activity against various oxygen reactive species and to inhibit LDL oxidation. This antioxidant action was largely ascribed to its Cu＾(2+)-binding property. However, relatively little is known of its effect on lipoprotein oxidation. In the present study, we investigated whether DAHK exerts protective effect on both LDL and HDL oxidation and attempted to elucidate the mechanism underlying antioxidant activity of DHAK. Our results show that DAHK exhibits a remarkable protection against LDL oxidation induced by Cu＾(2+). The concentration required to effectively prevent LDL oxidation is equivalent to that of Cu＾(2+), further emphasizing Cu＾(2+)chelation of DHAK. It was also observed that DAHK protected AAPH-induced LDL oxidation, suggesting that the protective action of DARK is likely related to scavenging activity in addition to Cu＾(2+) sequestration. Consistent with results observed with LDL oxidation, DARK demonstrated a significant prevention against Cu＾(2+)-induced HDL oxidation, although to lower extent. It is noteworthy that DAHK was found to exhibit a remarkable protection against PON1 inactivation by various reactive oxygen species-generating systems, underscoring the importance of its antioxidant activity. In support of its antioxidant potential, DARK was also observed to effectively prevent the HOCI-induced modification of Apolipoprotein A-I as evidenced by restoration of fluorescence. Taken together, our data indicate that DARK is highly effective in protecting lipoprotein oxidation and this protective effect results from both its Cu＾(2+) chelation and scavenging activity.
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KEYWORD
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paraoxonase 1 (PON1), high density lipoprotein, oxidative inactivation, protective action, peptide
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