The chemical is hydrogen peroxide (H2O2), the active
ingredient in color safe bleach. Produced in all animal
cells, hydrogen peroxide may act as a signal for the active
and resting phases of living things, new research by USC
biologists suggests.
A study published in the journal PLoS ONE shows that
hydrogen peroxide given to fruit flies has dramatic effects
on their daily rhythms and activity levels.
"
H2O2 might be functioning as a systemic signal by which
rhythms are regulated within cells and between cells," said
lead author John Tower, associate professor in molecular and
computational biology at USC College.
Most people are familiar with the concept of a
circadian
rhythm that governs sleeping and waking. But that is not the
only circadian rhythm in the body.
Many organs and tissues within the body have their own
independent circadian rhythms, and they also interact to
coordinate their rhythms.
Tower's study suggests a link between metabolism -- the
production of energy by mitochondria, often described as the
energy factories inside cells -- and an animal's daily
rhythms.
Mitochondria produce hydrogen peroxide as a by-product of
oxygen combustion, making the chemical a candidate signal
molecule.
"This is a logical way to connect rhythms to metabolism,"
Tower said.
"We know a lot about how
circadian rhythms are regulated
within certain cells. However, we have very little
information on what signals coordinate circadian rhythms and
how these rhythms are linked between metabolism and
behavior."
For the rhythms of even two cells to agree, some sort of
signal has to pass between them.
Tower's research group set out to find the signal by probing
the action of an enzyme in mitochondria that converts toxic
by-products of the body's combustion process into hydrogen
peroxide, itself a harmful but less toxic substance which
other defenses later break down further.
Tower and his team had noticed that overexpression of the
enzyme, known as superoxide dismutase (SOD), boosted the
activity level of fruit flies and even increased the life
span of certain genetically engineered strains.
Tower suspected that
hydrogen peroxide was the key
ingredient in SOD's action.
"Hydrogen peroxide is a great candidate for a signaling
molecule that would be involved in rhythms and behaviors.
It's the most stable and diffusible of the reactive oxygen
species (by-products of combustion), but no one had
demonstrated a role for it."
As a test, Tower's group administered
hydrogen peroxide
directly to fruit flies through feeding and injection.
The researchers observed similar effects from the direct
administration of hydrogen peroxide and the over-expression
of the SOD enzyme.
Both strategies increased the activity levels of adult
flies. Long-term direct treatment with hydrogen peroxide
suppressed daily rhythms, while SOD over-expression altered
those rhythms.
Tower explained that he had not expected identical results
from direct treatment versus genetic over-expression.
"I think it's just a little too crude of an intervention, to
feed them or inject them with the drug," he said, because
those effects will not be rhythmic, whereas production of
hydrogen peroxide by the mitochondria and by SOD is expected
to be rhythmic and to correspond to the rhythm of
metabolism.
Still, the similarities in the flies' reactions to direct
treatment and to SOD over-expression suggested to the
researchers that hydrogen peroxide is the crucial chemical.
"It's a very exciting result for us that our data now start
to point to hydrogen peroxide as perhaps being a relevant
signaling molecule for coupling metabolism to behaviors and
rhythms in the animal," Tower said.
Hydrogen peroxide would govern rhythms inside each cell as
well as between cells, Tower added.
Every cell alternates between a metabolic phase -- in which
it burns oxygen to make energy -- and a detoxification phase
in which the cell breaks down the harmful by-products of
combustion.
Those rhythms must be coupled with the energy-producing
activity of the mitochondria.
"Because hydrogen peroxide is produced by mitochondria as a
product of metabolism, it's a great candidate for a relevant
signal that might be modulating these cellular rhythms,"
Tower said.
Tower's group was able to correlate fly activity and
hydrogen peroxide concentration precisely through a unique
three-dimensional movement tracking system developed by
first author and doctoral student Dhruv Grover.
Doctoral students Daniel Ford, Nicholas Hoe and Aysen Erdem
and undergraduate Christopher Brown also contributed to the
study. Simon Tavare, professor of mathematics and molecular
and computational biology at USC College, designed and
supervised the statistical analyses.
