Volume 8 Issue 1 (pdf) - Andrew John Publishing Inc

| researCh and deVeLoPMent foCus
The Biology of Oxidative Stress:
Lessons from the Proteins of the Cochlea – Or, What Every
Audiologist Wants To Know about Auditory Biochemistry
By Donald Coling, PhD
dcoling@buffalo.edu
My essay is written for audiologists
and dedicated to my audiology
teacher, my colleague, and my friend,
Donald Henderson. It was presented as
an oral seminar on April 20, 2012 in
Buffalo at the Donald Henderson Noise-
Induced Hearing Loss Colloquium in
honor of Dr. Henderson’s retirement from
the Center for State University of New
York at Buffalo. Although the essay
focuses on damage to proteins, we would
be remiss not to briefly mention the
importance of oxidative damage to lipids
and DNA. We can’t escape the influence
of molecular biology and chemistry on
our lives. We don’t have to understand the
chemistry in detail, but, we’ve reached a
time when we have already begun to treat
hearing disorders with chemistry. As
hearing professionals, it behooves us to be
aware of a few basic ideas in auditory
biochemistry. I’ve tried to present them in
a painless and easy-to-read manner that
should help give some perspectives in the
practice of modern audiology.
About the Author
Don Coling is a research associate professor,
Center for Hearing and Deafness, Department
of Communicative Disorders and Sciences,
University at Buffalo, the State University of
New York.
sourCes of oxidatiVe
MetaBoLites
Radiation, toxic chemicals, and hyperactivity,
can induce oxidative stress
characterized by the production or
accumulation of reactive oxygen species
(ROS). ROS is the name given to oxygen
containing molecules that have a
particularly high chemical reactivity. The
most frequently studied ROS are
superoxide and nitric oxide. Superoxide
is produced when oxygen gains an
electron from cellular enzymes in
mitochondria, peroxisomes, nuclei and
cytoplasm. Nitric oxide is produced
when nitrogen is removed from the
amino acid arginine in the cytoplasm by
nitric oxide synthases. ROS are used at
low levels as physiological signalling
molecules before being degraded by
antioxidant enzymes. ROS are effective
signalling molecules because their
reactive electron structure and short
lifetime allows them to quickly combine
with nearby cellular proteins, change the
protein’s surface charge and shape, and
thereby change its function by affecting
the strength of interactions with other
proteins that depends on surface charge
and shape. If the level of ROS is low, cells
can rapidly degrade the signal and
activate an antioxidant response in
preparation for higher levels of ROS – a
state of preparedness. However, if the
level of oxidative metabolites is too high,
ROS can combine with each other and
with other molecules to form a variety of
metabolites, giving rise to irreversible
oxidative damage to proteins, lipids, and
nucleic acids.
The title of this essay, the “Biology of
Oxidative Stress,” is an enormous topic
that has produced over 200,000 research
articles indexed by the National Library
of Medicine over the last 60+ years. This
article will focus on only one aspect in
this large arena and that is oxidative
damage to proteins in the cochlea. We are
particularly interested in damage to outer
hair cells because they are typically the
most vulnerable to environmental insults
to the inner ear.
ros and hearing Loss
Several lines of evidence have
underscored the importance of ROS in
cochlear pathologies. Purturbations that
generate hearing loss include ionizing
radiation and heat, toxic chemicals,
hyperactivity from noise and loud music,
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