ASCB 2013 PressBook - page 11

T H E A M E R I C A N S O C I E T Y F O R C E L L B I O L O G Y
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12
News from
The American Society
for Cell Biology
53rd Annual Meeting
New Orleans, LA
December 14–18, 2013
Bursting the ROS bubble
in chronic wounds
EMBARGOED
FOR RELEASE
10:00 am, U.S. Central Time
Tuesday, December 17, 2013
Contact
Manuela Martins-Green
Professor of Cell Biology
Laboratory of Wound Healing
Biology
Department of Cell Biology
and Neuroscience
BSB Room 2117
University of California
Riverside, CA 92521
(951) 827-2585
Author Presents
Tuesday, December 17, 2013
12:00 PM–1:30 PM
Thread: Medicine
Defining Therapeutic Targets
and New Therapeutics
Presentation 2318
Poster B1325
Exhibit Halls B–D
Creating and reversing diabetic
chronic wounds by manipulation
of redox parameters
S. Dhall
1,2
, D. C. Do
3
, M. Garcia
2
,
N. Schiller
3
, M. M. Green
1,2
1
Bioengineering Interdepart-
mental Graduate Program, UC
Riverside, Riverside, CA
2
Cell Biology and Neuroscience,
UC Riverside, Riverside, CA
3
Division of Biomedical
Sciences, UC Riverside,
Riverside, CA
Controlling levels of reactive oxygen
species weakens bacterial biofilms
and breaks cycle of unhealing
wounds
I
t may begin as a “simple” foot blister, but
for patients with type 2 diabetes there is
nothing simple about wounds that won’t
heal. That blister can evolve into a seriously
infected wound that refuses to heal and, if
gangrene develops, the patient’s foot may
have to be amputated. Such “simple” foot
blisters and other diabetic ulcers or sores
account for the vast majority of foot and leg
amputations in the U.S. today. Paraplegics,
quadriplegics, and anyone with severely
limited mobility are also highly vulnerable to
these chronic skin wounds as well as pres-
sure ulcers and bedsores. Together, chronic
wounds affect an estimated 6.5 million Amer-
icans at an annual cost of about $25 billion.
Two biological activities are out of con-
trol in chronic wound infections, says Manu-
ela Martins-Green of the University of Cali-
fornia, Riverside (UC Riverside)—reactive
oxygen species (ROS), which are chemically
reactive molecules formed by the partial
reduction of oxygen, and biofilms that are
formed by selective invading bacteria. ROS,
the natural byproduct of normal oxygen
metabolism, plays a role in cell signaling
and homeostasis. However, previous studies
have shown that excessive ROS can induce
chronic inflammation, a key characteristic
of wounds that do not heal. The biofilms
are bacterial defense mechanisms. Together
they create a sealed toxic environment
that can resist all efforts to heal and close
a chronic wound. But by controlling ROS
levels within the wound, Martins-Green
now reports that her UC Riverside lab was
able to normalize conditions and heal
chronic wounds in genetically modified
mouse models. Decreasing ROS to normal
levels resulted in significant improvement
in wound healing.
The researchers identified the central
role of ROS in maintaining chronic wound
infection by inhibiting glutathione peroxi-
dase and catalase, antioxidant enzymes
that help maintain normal tissue levels
of ROS. Because the antioxidant enzymes
were inhibited, the amount of ROS in the
wounds soared. The scientists also found
that the antioxidant inhibitors were more
damaging if administered in combination
rather than individually.
The researchers then decreased ROS
to normal levels by applying two strong
antioxidant supplements, vitamin E and
N-Acetyl cysteine. Vitamin E reduces the
levels of the oxygen radicals, and N-Acetyl
cysteine stabilizes the antioxidant enzyme
pool, which helps decrease the hydrogen
peroxide levels, a contributor to oxidative
damage. As a result of the antioxidant treat-
ment, glutathione peroxidase and catalase
activities were restored, and the bacterial
biofilm disintegrated in the wound, says
Martins-Green. This leads to development
of healthier wound tissue.
These results show for the first time
that, by deliberately modulating specific
redox parameters, the researchers were
able to create chronic wounds and then
reverse chronicity by antioxidant treat-
ment. “Our findings emphasize the impor-
tance of maintaining redox balance during
healing and will
help in unraveling
the mechanisms
underlying the
development of
chronic wounds
and hence in
identifying po-
tential targets
for treatment of
these wounds in
humans,” says
Martins-Green.
The diabetic chronic wounds had elevated levels of oxidative stress and presence of biofilm
forming bacteria (“shield”) that provide protection from antibiotic treatment. Manipulat-
ing the wound microenvironment by treating it with antioxidants reversed the pathway of
chronicity to a path of proper healing.
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