Investigating the Mechanism of Action of Colostrinin™ on Cells in Culture

Froud, Kristina Elizabeth (2009). Investigating the Mechanism of Action of Colostrinin™ on Cells in Culture. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.0000f256

Abstract

The aim of this Ph.D. project was to investigate the effects of Colostrinin (CLN) on cells in culture, and its Aβility to prevent or alleviate cytotoxicity induced by reactive oxygen species (ROS) and beta-amyloid (Aβ). Two cell culture systems were used to analyse the effects of CLN; rat primary hippocampal cultures and the B50 rat neuronal cell line.

Bovine CLN was found to have no adverse effects on cell morphology or survival and to have a small, non-significant effect, on both menadione-induced, oxidative stress-mediated toxicity and Aβ1-42-induced toxicity of neurons in primary hippocampal cultures. This protective effect was found to potentially be related to the antioxidant effects of CLN. CLN was demonstrated to prevent a menadione-induced increase in ROS in the B50 cell line. Furthermore CLN was able to reverse a significant Aβ1-42-mediated increase in the protein levels of the antioxidant enzyme Cu/Zu superoxide dismutase (SOD) in primary hippocampal cultures, although CLN alone caused an increase in SOD1 protein in the B50 cell line.

Bovine CLN was shown, in both B50 cells and primary hippocampal cells, not to significantly decrease the protein levels of cyclin dependent kinase 5 (Cdk5) which has previously been demonstrated to be involved in the mechanism of tumour necrosis factor (TNF) α-mediated protection against Aβ-induced toxicity in primary hippocampal cultures. Furthermore CLN did not consistently alter the expression of activated caspase 3 in either B50 or primary hippocampal cells.

This study adds to the knowledge and understanding of the mechanism of action of CLN.