Overexpression of peroxiredoxins I, II, III, V, and VI in malignant mesothelioma

Abstract

Peroxiredoxins (Prxs) are a recently characterized group of thiol-containing proteins with efficient antioxidant capacity, capable of consuming hydrogen peroxide in living cells. Altogether six distinct Prxs have been characterized in mammalian tissues. Their expression was investigated in histological samples of mesothelioma and in cell lines established from the tumours of mesothelioma patients. Four cases with histopathologically healthy pleura from non-smokers were used as controls. Healthy pleural mesothelium was negative or very weakly positive for all Prxs. In mesothelioma, the most prominent reactivity was observed with Prxs I, II, V, and VI. Prx I was highly or moderately expressed in 25/36 cases, the corresponding figures for Prxs II-VI being 27/36 (Prx II), 13/36 (Prx III), 2/36 (Prx IV), 24/36 (Prx V), and 30/36 (Prx VI). Positive staining was observed both in the cytosolic and the nuclear compartment, with the exception of Prx III, which showed no nuclear reactivity. The staining pattern of Prxs III and V was granular. Immunoelectron microscopic localization of Prxs was in accordance with the immunohistochemical findings, showing diffuse cytoplasmic localization for Prxs I, II, IV, and VI and distinct mitochondrial labelling for Prxs III and V. There was no significant association between the extent of staining and different Prxs. It appeared that Prxs may not have prognostic significance, but being prominently expressed in most mesotheliomas these proteins, at least in theory, may play a role in the primary drug resistance of this disease.

Impaired homeostasis and phenotypic abnormalities in Prdx6−/−mice lens epithelial cells by reactive oxygen species: increased expression and activation of TGFβ

“…These enzymes reduce peroxides to the corresponding alcohol or water. [4][5][6][7][8] The PRDX family displays special features, compared with other existing peroxidases. Specifically, when reducing H 2 O 2 , PRDX enzymes themselves are oxidized, therefore acting both as peroxidase and co-substrate.…”

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).…”

Molecular characterization and expression analysis of six peroxiredoxin paralogous genes in gilthead sea bream (Sparus aurata): Insights from fish exposed to dietary, pathogen and confinement stressors

“…PRDX1 and 2, also referred as natural killer enhancing factors (NKEF-A, NKEF-B), are localized in the cytosol [6,7], whereas the other members of the 2-Cys PRDX subclass are widely distributed with PRDX3 in mitochondria [8], PRDX4 in endoplasmatic reticulum and extracellular space [9] and PRDX5 in cytosol, mitochondria and peroxisomes [10]. In contrast, PRDX6 is restricted to cytosol [11], and the catalytic efficiency of all PRDXs is less than that of catalase or glutathione peroxidases by one or three orders of magnitude [12].…”