Thioredoxin Peroxidase Is a Novel Inhibitor of Apoptosis with a Mechanism Distinct from That of Bcl-2

Abstract

Thioredoxin peroxidase (TPx) is a member of a newly discovered family of proteins that are conserved from yeast to mammals and to which natural killer enhancing factor belongs. These proteins are antioxidants that function as peroxidases only when coupled to a sulfhydryl reducing system. The physiological function of TPx in cells is not yet known. Here we demonstrate that when the human TPx II, a member of this family, is stably overexpressed in Molt-4 leukemia cells, it protects from apoptosis induced by serum deprivation, ceramide, or etoposide. TPx II, like Bcl-2, is able to inhibit release of cytochrome c from mitochondria to cytosol, and it inhibits lipid peroxidation in cells. TPx II, unlike Bcl-2, could prevent hydrogen peroxide accumulation in cells, suggesting that it functions upstream of Bcl-2 in the protection from apoptosis and may be implicated as an endogenous regulator of apoptosis.

Distinct gene signature revealed in white blood cells, CD4+ and CD8+ T cells in (NZBx NZW) F1 lupus mice after tolerization with anti-DNA Ig peptide

“…43 In addition, Prdx2 has been reported to have an important role in the inhibition of apoptosis in a novel pathway distinct from Bcl-2. 44,45 The increased expression of Prdx2 following treatment with pCons might shed light on the mechanism by which peptide tolerization decreases apoptosis.…”

Oxidative and nitrosative stress induces peroxiredoxins in pancreatic beta cells

“…Prx enzymes have been identified in association with various cellular functions apparently unrelated to peroxidase activity. Several lines of evidence support the concept that peroxiredoxins can influence cell proliferation and differentiation, immunological defence, receptor signalling and apoptosis [10,23,26,27,28,29]. This is reflected by the numerous synonyms used.…”

“…Prx II is important in erythroid cell differentiation [11,26] and protects red blood cell membranes from peroxidation [20,45]. It also regulates signal transduction pathways that directly relate to apoptotic cell death [23,27,28,29,46]. Prx II is thought to protect neuronal cells against destruction by hypoxia and ischaemia [11,47] and tumour cells against X-ray treatment and chemotherapy [48].…”

Structure, organization and expression of common carp (Cyprinus carpio L.) NKEF-B gene

“…NKEF-A and -B, later identified as PrxI and PrxII respectively [6], can be detected in a wide range of tissues [7,8]. The NKEF protein may be also involved in apoptosis [9,10], cell proliferation, differentiation [11,12] and anti-viral activity in vitro [13]. Although recombinant NKEF (rNKEF)-A and -B have similar levels of antioxidant function, only the reduced form of rNKEF-A can enhance NK cytotoxicity, which indicates that both the antioxidant and NK-enhancing functions of rNKEF-A and -B probably involve the cysteine residues of the proteins but are mediated by separate domains of the molecules [14].…”