Stable expression of a novel fusion peptide of thioredoxin-1 and ABAD-inhibiting peptide protects PC12 cells from intracellular amyloid-beta.
Amyloid-beta peptide-binding alcohol dehydrogenase (ABAD) inhibiting peptide, as a specific inhibitor between ABAD and amyloid-beta (Abeta), has been demonstrated to effectively inhibit Abeta peptide cytotoxicity. However, a major drawback is its short half-life, which results in the need for multiple applications and high synthesis costs. To overcome this, we established a lentiviral expression system that allowed the stable expression of the small ABAD-inhibiting peptide by fusion with cytosolic thioredoxin-1 (TRX). The fusion peptide, TA aptamer, was observed within PC12 cytoplasm and maintained both Abeta-binding ability and antioxygenic property similar to TRX. Our data showed that overexpression of both TRX and TA aptamer could protect PC12 cells from intracellular Abeta cytotoxicity. The present study suggests that TRX, as a cytosolic protein and a fusion motif, could not only assist ABAD-inhibiting peptide expression, cytoplasmic localization, but rebalance the disturbed "redox equilibrium" caused by intracellular Abeta in PC12 cells.
Yang
Xin
X
Department of Neurology, the First Hospital, Jilin University, Changchun, China.
Yang
Yu
Y
Wu
Jiang
J
Zhu
Jie
J
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D052158:Aptamers, Peptide / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008958:Models, Molecular; D018696:Neuroprotective Agents / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism; D016716:PC12 Cells; D010446:Peptide Fragments / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051381:Rats; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D052158:Aptamers, Peptide; D018696:Neuroprotective Agents; D016877:Oxidants; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D013879:Thioredoxins; D006861:Hydrogen Peroxide; D015094:3-Hydroxyacyl CoA Dehydrogenases; C108634:HSD17B10 protein, human