Date of Award
8-1-2010
Document Type
Masters Thesis
Degree Name
M.S.
Organizational Unit
College of Natual Science and Mathematics
First Advisor
Daniel A. Linseman, Ph.D.
Second Advisor
Nancy Lorenzon
Third Advisor
Joseph Angleson
Fourth Advisor
Byron Purse
Keywords
Apoptosis, Mitochondrial oxidative stress, Neuronal death, Nutraceutical antioxidants
Abstract
Neurodegenerative diseases such as Parkinson’s and amyotrophic lateral sclerosis have devastating consequences to the afflicted patients. A major cellular pathophysiology underlying these diseases is mitochondrial oxidative stress (MOS) leading to neuronal death. Here, we investigated the neuroprotective effects of a novel class of nutraceuticals, anthocyanins, against MOS-induced death in primary cultures of rat cerebellar granule neurons (CGNs). Anthocyanins are natural antioxidants whose neuroprotective potential has yet to be examined in detail. Kuromanin and callistephin are anthocyanins derived from black rice and strawberries, respectively. Glutathione (GSH)-sensitive MOS and intrinsic apoptosis were induced in CGNs by the Bcl-2 inhibitor, HA14-1. Callistephin and kuromanin each demonstrated significant neuroprotection from this MOS-induced death that was equal to that provided by the green tea polyphenol, epigallocatechin 3-gallate; however, neither anthocyanin was as effective as GSH at rescuing CGNs. Incubation with HA14-1 alone resulted in nearly 90% apoptosis of CGNs and either callistephin or kuromanin reduced this effect to approximately 20% cell death. Treatment with HA14-1 caused a marked depletion of mitochondrial GSH in CGNs to approximately 40% of the control level. Callistephin and kuromanin essentially prevented the reduction in this critical pool of endogenous antioxidant. These data indicate that callistephin and kuromanin represent a new class of neuroprotective compounds that warrant further study as possible therapeutic agents for the treatment of neurodegenerative diseases caused by MOS.
Publication Statement
Copyright is held by the author. User is responsible for all copyright compliance.
Rights Holder
Natalie A. Kelsey
Provenance
Received from ProQuest
File Format
application/pdf
Language
en
File Size
69 p.
Recommended Citation
Kelsey, Natalie A., "Neuroprotective Effects of Anthocyanins on Neuronal Death Induced by Inhibition of Bcl-2 and Oxidative Stress" (2010). Electronic Theses and Dissertations. 333.
https://digitalcommons.du.edu/etd/333
Copyright date
2010
Discipline
Neurosciences