Abstract
Non-bullous congenital ichthyosis erythroderma (NCIE) and lamellar
ichthyosis (LI) are characterized by mutations in 12R-lipoxygenase
(12R-LOX) and/or epidermal lipoxygenase 3 (eLOX3) enzymes. The eLOX3
lacks oxygenase activity, but is capable of forming hepoxilin-type
products from arachidonic acid-derived hydroperoxide from 12R-LOX,
termed 12R-hydroperoxyeicosa-5,8,10,14-tetraenoic acid (12R-HpETE).
Mutations in either of two enzymes lead to NCIE or LI. Moreover,
12R-LOX-deficient mice exhibit severe phenotypic water barrier dysfunctions.
Here, we demonstrate that 12R-HpETE can also be transformed to 8R-HXA(3)
by hepoxilin A(3) (HXA(3)) synthase (12-lipoxygenase), which exhibits
oxygenase activity. We also presented a novel form of ichthyosis
in a patient, termed hepoxilin A(3) synthase-linked ichthyosis (HXALI),
whose scales expressed high levels of 12R-LOX, but were deficient
of HXA(3) synthase.
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