The RGD-containing peptide fragment of osteopontin protects tyrosine hydroxylase positive cells against toxic insult in primary ventral mesencephalic cultures and in the rat substantia nigra.

Journal of Neurochemistry
Joanna IczkiewiczPeter Jenner

Abstract

We have previously shown that the multi-functional phosphoprotein osteopontin (OPN) is present in the substantia nigra (SN) and that its mRNA and protein expression are up-regulated following toxic insult. We now report the effects of the arginine-glycine-aspartic acid (RGD)-containing peptide fragment of OPN and OPN inactivation on the survival of tyrosine hydroxylase (TH) positive neurones in primary rat ventral mesencephalic (VM) cultures and in SN in the rat. Treatment of VM cultures with the fragment of OPN containing the RGD integrin binding domain did not decrease TH positive cell number, but instead the peptide fragment protected against cell loss induced by both MPP(+) and lipopolysaccharide (LPS). Incorporation of an OPN antibody into VM cultures caused a concentration-dependent loss of TH positive neurones. The OPN antibody also exacerbated MPP(+) - and LPS-induced cell loss at all concentrations tested. In the rat, administration of the RGD-containing peptide fragment of OPN protected TH positive neurones against a mechanically-induced lesion and against 6-hydroxydopamine- and LPS-induced cell loss. The protection against 6-hydroxydopamine toxicity was confirmed in a separate study using stereological analysis. By c...Continue Reading

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Citations

May 4, 2012·Cellular and Molecular Neurobiology·Toshihiko SuzukiHiroyuki Ichikawa
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Jun 29, 2021·Frontiers in Cell and Developmental Biology·Hongzhen ChenChao Liang

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