10 / 19
allied
academies
Page 40
Notes:
April 17-18, 2019 | Frankfurt, Germany
Parkinson’s, Huntington’s & Movement Disorders
International Conference on
Journal of Brain and Neurology | Volume 3
Pharmacological correction of Mitochondrial Dysfunction in rotenone model of
Parkinson’s disease: potential participation of P53, NF κB and Nrf2
Olga Gonchar
and
Iryna Mankovska
Bogomoletz Institute of Physiology National Academy of Sciences of Ukraine, Ukraine
M
itochondrial dysfunction has been widely
implicated in the neuronal degeneration
in Parkinson’s disease (PD). Mitochondria-
targeted protective compounds that prevent or
minimize a wide range of mitochondrial defects
constitute new therapeutic strategies in the
prevention and treatment of such degeneration.
The antioxidant mexidol (2-ethyl-6-methyl-3-
hydroxypyridine succinate) is used in clinical practice
as a neuroprotector due to its positive influence
on the brain energetic metabolism and free radical
processes. However, its application as mitochondria-
targeted agent to prevent or treat of PD had not
been studied yet. We have used rotenone long-term
administration as a rat model of PD to investigate
in brain mitochondrial oxidative stress intensity,
protein expression/activity of antioxidant enzymes-
manganese superoxide dismutase (MnSOD),
glutathione peroxidase (GPx), and antiapoptotic
Bcl-2 as well as protein expression of their upstream
regulators: P53, Nrf2 and NF-kB. Rotenone
intoxication induced an increase in ROS formation,
lipid peroxidation, H2O2 production and a decrease
in GSH/GSSG ratio, mitochondrial aconitase activity
as well as disorders in mitochondrial antioxidant
status (reduced MnSOD, GPx activities/protein
content and mRNA expression). In parallel with P53
mitochondrial translocation, we found a decrease
in Bcl-2 protein level, an enhance in nuclear
accumulation of the phosphorylated NF κB p65
protein. Under the action of rotenone with mexidol,
there was demonstrated a reduction in oxidative
stress biomarkers, elevation of antioxidant capacity
by an increase in protein expression of Nrf2 and its
targets (MnSOD and GPx). In brain mitochondria
Mexidol interrupted apoptotic cascade by lowering
of P53 protein accumulation as well as increasing
Bcl-2 protein content. Simultaneously we registered
some decline in NF κB p65 protein level in nuclear
extracts of brain cells. The efficacy of mexidol
determined in the rotenone model of PD may be
explain by its ability to influence on mitochondrial
redox status and in that way modulate many
signaling pathways in brain cells.
Speaker Biography
Olga Gonchar is a senior researcher, Department of Hypoxia, Bogomoletz
Institute of Physiology National Academy of Sciences of Ukraine, and
she studied mechanisms of correction of tissue hypoxia by common use
of biomembrane stabilizators and antioxidants; studied the methods
of adaptation to hypoxia (high altitude stay and intermittent hypoxia)
and their use in medicine and sports; studied the genetic and epigenetic
mechanisms of the oxygen-dependent cell processes regulation under
adaptation to hypoxia and oxidative stress; experimental and clinical
(Parkinson’s disease and Diabetes mellitus) investigation of mitochondrial
dysfunction development under hypoxia and oxidative stress.
e:
olga.gonchar@i.ua