"Imbalance in the antioxidant capacity"

Small molecular antioxidants effectively protect from PUVA-induced
oxidative stress responses underlying fibroblast senescence and
photoaging
Free Radical Biology and Medicine, Volume 45, Issue 5, 1 September
2008, Pages 636-644
Stefania Briganti, Meinhard Wlaschek, Christina Hinrichs, Barbara
Bellei, Enrica Flori, Nicolai Treiber, Sebastian Iben, Mauro Picardo,
Karin Scharffetter-Kochanek

Abstract
Exposure of human fibroblasts to 8-methoxypsoralen plus ultraviolet-A
irradiation (PUVA) results in stress-induced cellular senescence in
fibroblasts.
We here studied the role of the antioxidant defense system in the
accumulation of reactive oxygen species (ROS) and the effect of the
antioxidants α-tocopherol, N-acetylcysteine, and α-lipoic acid on PUVA-
induced cellular senescence.
PUVA treatment induced an immediate and increasing generation of
intracellular ROS.
Supplementation of PUVA-treated fibroblasts with α-tocopherol (α-Toc),
N-acetylcysteine (NAC), or α-lipoic acid (α-LA) abrogated the
increased ROS generation and rescued fibroblasts from the ROS-
dependent changes into the cellular senescence phenotype, such as
cytoplasmic enlargement, enhanced expression of senescence-associated-
β-galactosidase and matrix-metalloproteinase-1, hallmarks of
photoaging and intrinsic aging. PUVA treatment disrupted the integrity
of cellular membranes and impaired homeostasis and function of the
cellular antioxidant system with a significant decrease in glutathione
and hydrogen peroxide-detoxifying enzymes activities.
Supplementation with NAC, α-LA, and α-Toc counteracted these changes.
Our data provide causal evidence that (i) oxidative stress due to an
imbalance in the overall cellular antioxidant capacity contributes to
the induction and maintenance of the PUVA-induced fibroblast
senescence and that (ii) low molecular antioxidants protect
effectively against these deleterious alterations.

----------------------------

"UVA-induced necrotic cell death reflects the intracellular level of
LIP (iron) "

J Invest Dermatol. 2004 Oct;123(4):771-80.
Susceptibility of Skin Cells to UVA-induced Necrotic Cell Death
Reflects the Intracellular Level of Labile Iron.

Zhong JL, Yiakouvaki A, Holley P, Tyrrell RM, Pourzand C.

Department of Pharmacy and Pharmacology, University of Bath, Bath,
UK.

The mechanism of resistance of keratinocytes to ultraviolet A (UVA)
(320-400 nm)-induced oxidative damage has not yet been elucidated.
Here, we examined the possible link between the intracellular level of
the labile iron pool (LIP) and the susceptibility to UVA-induced cell
death using a series of human skin fibroblast and keratinocyte cell
lines as a model.
Resistance of keratinocytes to UVA-induced cell death was confirmed by
flow cytometry and in fibroblasts necrosis was found to be the primary
mode of cell death induced by UVA.
The percentage of necrosis in fibroblasts also correlated with the
extent of intracellular ATP depletion, a hallmark of necrotic cell
death.
The evaluation of the intracellular level of LIP by calcein assay
revealed that both "basal" and "UVA-induced" levels of LIP in
keratinocytes were several fold lower than
in fibroblasts.
Accordingly the dose to give an equivalent level of
necrosis was several fold lower in fibroblasts than in keratinocytes.
Furthermore, the modulation of "basal" or "UVA-induced" level of LIP
by either Desferal and/or hemin treatment significantly affected the
extent of UVA-induced necrotic cell death and ATP depletion in all the
cell lines.
Cellular susceptibility to UVA-induced necrotic cell death appears to
reflect the intracellular level of LIP.

PMID: 15373784 [PubMed - in process]

---------------------------------------

The trials initially will focus on individuals with the autoimmune
disease
lupus, who are extremely sensitive to the sun.
<<snip>>

UNIVERSITY OF FLORIDA AND PROCTER & GAMBLE TEAM UP AGAINST SKIN
CANCER

Feb. 11, 2002
Contact Information

--------------------------------------------------------------------------
------

"lupus who are extremely sensitive to the sun"

GAINESVILLE, Fla. --- The University of Florida and Procter & Gamble
today announced they have joined forces to advance research on
Photoprotective Iron Chelator Technology, which was developed by P&G
and shows promise for preventing or reducing the harmful effects of
the sun, particularly skin
cancer.

Preliminary research has shown that, in combination with the
appropriate sunscreen, Photoprotective Iron Chelator Technology, or
PICT, may have the potential to decrease the number of individuals who
develop skin cancer by greatly delaying or preventing tumor onset. It
may also reduce the number of
tumors in those who do develop skin cancer. The safety and efficacy of
PICT must be demonstrated in clinical trials, and the product will
ultimately
require review and approval by the Food and Drug Administration.

http://tinyurl.com/5fdrse

Who loves ya.
Tom

Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh

Man Is A Herbivore!
http://tinyurl.com/4rq595

DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk