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Antioxidants on
Photoaging Prevention
Kang, Sewon1,
Fisher, Gary1 and Voorhees, John 1
University of Michigan Medical Center1
Abstract-
Photoaging refers to premature skin aging caused by repeated exposures
to solar ultraviolet (UV) radiation. Both fine and coarse wrinkles are
a characteristic feature of photodamaged skin and the major histologic
alterations are localized in the connective tissue. Activation of cell
surface receptor tyrosine kinases and generation of reactive oxygen
species (ROS) are two of the earliest effects of UV on human skin in
vivo. Receptor activation and ROS then stimulate MAP kinase (JNK, ERK,
p38) signal transduction pathways that upregulate transcription factor
AP-1 and its target, matrix metalloproteinase (MMP) genes in human skin.
MMP-mediated dermal matrix degradation is believed to be the major contributor
to photoaging. Therefore, agents that can neutralize ROS (antioxidants)
and/or inhibit tyrosine kinase may mitigate UV sigaling pathways that
lead to photoaging. We investigated the ability of topical genistein
(GEN) and n-acetyl cysteine (NAC) to affect responses to UV (2MED) that
eventuate in photoaging in human skin in vivo. GEN possesses both tyrosine
kinase inhibitory and antioxidant activities, and NAC can be converted
into endogenous antioxidant glutathione. UV-induced epidermal growth
factor receptor (EGF-R) phosphorylation in human skin was inhibited
by pretreatment with GEN (5%) but not NAC (20%). Prior to UV, GEN treatment
prevented activation of MAP kinases (ERK and JNK), cJun protein induction,
and MMP expression. Pretreatment with NAC provided results similar to
GEN, except JNK activation by UV was unaffected. Thus in human skin
in vivo, GEN and NAC block early UV responses (EGF-R and MAP kinase
activation) that ultimately lead to MMP gene expression. These data
indicate that compounds like GEN and NAC which possess antioxidant and/or
tyrosine kinase inhibitory activies, may prevent photoaging.
Keywords: antioxidant,
photoaging, genistein, n-acetyl cysteine
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