A novel type of glutathione peroxidase: expression and regulation during wound repair

Abstract

We have previously identified and cloned a novel keratinocyte growth factor (KGF)-regulated gene in human keratinocytes that encodes the human homologue of a bovine non-selenium glutathione peroxidase (GPx). To gain insight into the regulation of this gene in vivo, we isolated the murine homologue from a mouse skin cDNA library. In vitro transcription/translation demonstrated that the cDNA encodes a 27 kDa protein. Furthermore, we amplified by PCR a partial cDNA that most likely corresponds to a related gene. RNase protection analysis revealed tissue-specific expression of both genes and the occurrence of alternative splicing or RNA editing of at least one of the primary transcripts. Similar to that of KGF, expression of GPx was strongly induced after cutaneous injury, and each isoform displayed unique kinetics of expression during the repair process. In situ hybridization studies demonstrated high levels of GPx mRNA in keratinocytes of the hyperproliferative epithelium at the wound edge. Since these cells express functional KGF receptors, induction of GPx expression by KGF might also occur in vivo. These data suggest a role for GPx in the protection of epithelial cells against oxidative stress, particularly during the inflammatory phase of wound repair.

Loss of NF-κB Control and Repression of Prdx6 Gene Transcription by Reactive Oxygen Species-driven SMAD3-mediated Transforming Growth Factor β Signaling

“…This molecule is widely expressed, occurring in high levels in the liver, lung, eye lens, and keratinocytes (1,2,10,(12)(13)(14)(15)(16)(17)(18), whereas reduced expression of PRDX6 can lead to cell death and tissue degeneration (10, 11, 15, 19 -22). PRDX6 has been implicated in maintenance of blood vessel integrity in wounded skin (23,24) and in development and progression of several diseases, including oxidative-induced cataractogenesis (25), psoriasis (12,26) atherosclerosis (22), and Parkinsonian dementia (27). Accumulating evidence indicates that expression levels of PRDX6 contribute to pathophysiology of cells and tissues.…”

Activation of the antioxidant enzyme 1-CYS peroxiredoxin requires glutathionylation mediated by heterodimerization with πGST

“…This peroxiredoxin is expressed in all tissues but at particularly high levels in brain, eye, testes, and lung (2,7,8). Expression of 1-cysPrx protein or mRNA is decreased in a mouse that is susceptible to experimental atherosclerosis (9) and is elevated in brains of patients with Parkinsonian dementia (10), sporadic Creutzfeldt-Jacob disease (11), and Pick disease (12), in lungs from newborns (13), in malignant mesothelioma (14), in the healing edge of skin wounds (15), and in experimental cellular premature senescence (16). 1-cysPrx can reduce phospholipid and other hydroperoxides (6) and protects against cellular membrane damage (17,18).…”

Peroxiredoxin 6 Is a Potent Cytoprotective Enzyme in the Epidermis

“…Previous studies from our laboratory revealed a strong induction of prdx6 expression in cultured keratinocytes on treatment with keratinocyte growth factor. 19 In vivo, prdx6 is overexpressed in the hyperproliferative epidermis of skin wounds 20 and of psoriatic patients. 19 To determine the consequences of enhanced expression of this enzyme in keratinocytes, we generated transgenic mice overexpressing Prdx6 in the epidermis.…”