Biochem J. 2001 Feb 1;353(Pt 3):459-66.
Haem oxygenase-1: a novel player in cutaneous wound repair and psoriasis?
Hanselmann C, Mauch C, Werner S.
Institute of Cell Biology, Swiss Federal Institute of Technology, Hönggerberg,
CH-8093 Zürich, Switzerland.
Haem oxygenase (HO) is the rate-limiting enzyme in the degradation of haem. In
addition to its obvious role in iron metabolism,
a series of findings indicate an
important role for HO in cellular protection against oxidative stress. This
effect might be of particular importance during wound healing and also in
inflammatory disease. Therefore we determined the expression of the two HO
isoenzymes, HO-1 and HO-2, during the healing process of full-thickness
excisional wounds in mice. We show a remarkable induction of HO-1 mRNA and
protein expression within three days after skin
injury. After completion of wound
healing, HO-1 expression declined to basal levels. By contrast, expression of
HO-2 was not significantly modulated by skin injury. In situ hybridization and
immunohistochemistry revealed high HO-1 expression in inflammatory cells of the
granulation tissue and in keratinocytes of the hyperproliferative epithelium. A
strong overexpression of HO-1 was also observed
in the skin of patients suffering
from the inflammatory skin disease psoriasis. In
addition, HO-2 mRNA levels were
increased in the skin of psoriatic patients. Similar to wounded skin,
inflammatory cells and keratinocytes of the hyperthickened epidermis were the
major producers of HO-1 in psoriatic skin. In vitro studies with cultured
keratinocytes revealed a potential role for reactive oxygen species (ROS), but
not for growth factors and pro-inflammatory cytokines, as inducers of HO-1
expression in inflamed skin. Our findings suggest a novel role for HO in wound
healing and inflammatory skin disease, where it might be involved in haem
degradation and in the protection of cells from the toxic effects of ROS.
J Eur Acad Dermatol Venereol. 2003 Nov;17(6):663-9.
Antioxidant activity, lipid peroxidation and skin diseases. What's new.
Briganti S, Picardo M.
Cutaneous Physiopathology Laboratory, San Gallicano Dermatological Institute,
25/A Via S. Gallicano, 00153-Rome, Italy. You are not allowed to view links.
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LoginDue to its interface function between the body and the environment, the skin is
chronically exposed to both endogenous and environmental pro-oxidant agents,
leading to the harmful generation of reactive oxygen species (ROS). There is
compelling evidence that oxidative stress is involved in the damage of cellular
constituents, such as DNA, cell membrane lipids
or proteins. To protect the skin
against the over-load of oxidant species, it
contains a well-organised system of
both chemical and enzymatic antioxidant which are able to work in a synergistic
manner. Skin antioxidant network protects cells against oxidative injury and
prevent the production of oxidation products, such as 4-hydroxy-2-nonenal or
malonaldehyde, which are able to induce protein damage, apoptosis or release of
pro-inflammatory mediators, such as cytokines. When oxidative stress overwhelms
the skin antioxidant capacity the subsequent modification of cellular redox
apparatus leads to an alteration of cell homeostasis and a generation of
degenerative processes. Topical application or oral administration of
antioxidants has been recently suggested as preventive therapy for skin
photoaging and UV-induced cancer. The recognition that ROS can act as second
messengers in the induction of several biological responses, such as the
activation of NF-kB or AP-1, the generation of cytokines, the modulation of
signalling pathways, etc., has led many researchers to focus on the possible
effects of antioxidants in many pathological
processes. The recent demonstration
that the peroxisome proliferators-activated
receptors, whose natural ligands are
polyunsaturated fatty acids and theirs oxidation
products, have a central role in
the induction of some skin diseases, such as
psoriasis or acne, has indicated new
links between free radicals and skin inflammation. Based on these findings, the
review summarises the possible correlations
between antioxidant imbalance, lipid
oxidative breakage and skin diseases, from both a pathological and therapeutic
points of view
