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2015 ; 6
(ä): 297-310
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The role of lipoxygenases in pathophysiology; new insights and future
perspectives
#MMPMID26298204
Mashima R
; Okuyama T
Redox Biol
2015[Dec]; 6
(ä): 297-310
PMID26298204
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Lipoxygenases (LOXs) are dioxygenases that catalyze the formation of
corresponding hydroperoxides from polyunsaturated fatty acids such as linoleic
acid and arachidonic acid. LOX enzymes are expressed in immune, epithelial, and
tumor cells that display a variety of physiological functions, including
inflammation, skin disorder, and tumorigenesis. In the humans and mice, six LOX
isoforms have been known. 15-LOX, a prototypical enzyme originally found in
reticulocytes shares the similarity of amino acid sequence as well as the
biochemical property to plant LOX enzymes. 15-LOX-2, which is expressed in
epithelial cells and leukocytes, has different substrate specificity in the
humans and mice, therefore, the role of them in mammals has not been established.
12-LOX is an isoform expressed in epithelial cells and myeloid cells including
platelets. Many mutations in this isoform are found in epithelial cancers,
suggesting a potential link between 12-LOX and tumorigenesis. 12R-LOX can be
found in the epithelial cells of the skin. Defects in this gene result in
ichthyosis, a cutaneous disorder characterized by pathophysiologically dried skin
due to abnormal loss of water from its epithelial cell layer. Similarly, eLOX-3,
which is also expressed in the skin epithelial cells acting downstream 12R-LOX,
is another causative factor for ichthyosis. 5-LOX is a distinct isoform playing
an important role in asthma and inflammation. This isoform causes the
constriction of bronchioles in response to cysteinyl leukotrienes such as LTC4,
thus leading to asthma. It also induces neutrophilic inflammation by its
recruitment in response to LTB4. Importantly, 5-LOX activity is strictly
regulated by 5-LOX activating protein (FLAP) though the distribution of 5-LOX in
the nucleus. Currently, pharmacological drugs targeting FLAP are actively
developing. This review summarized these functions of LOX enzymes under
pathophysiological conditions in mammals.
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