This gene encodes a member of the peroxiredoxin family of antioxidant enzymes, which reduce hydrogen peroxide and alkyl hydroperoxides. The encoded protein may play an antioxidant protective role in cells, and may contribute to the antiviral activity of CD8(+) T-cells. This protein may have a proliferative effect and play a role in cancer development or progression. Three transcript variants encoding the same protein have been identified for this gene.
As enzymes that combat oxidative stress, peroxiredoxins play an important role in health and disease. Peroxiredoxin 1 and peroxiredoxin 2 have been shown to be released by some cells when stimulated by LPS or TNF-alpha. The released peroxiredoxin can then act to produce inflammatory cytokines. The levels of peroxiredoxin 1 are elevated in pancreatic cancer and it can potentially act as a marker for the diagnosis and prognosis of this disease. In some types of cancer, peroxiredoxin 1 has been determined to act as a tumor suppressor and other studies show that peroxiredoxin 1 is overexpressed in certain human cancers. A recent study has found that peroxiredoxin 1 may play a role in tumorigenesis by regulating the mTOR/p70S6K pathway in esophageal squamous cell carcinoma. The expression patterns of peroxiredoxin 1 along with peroxiredoxin 4 are involved in human lung cancer malignancy. It has also been shown that peroxiredoxin 1 may be an important player in the pathogenesis of acute respiratory distress syndrome because of its role in promoting inflammation.
^Prospéri MT, Ferbus D, Karczinski I, Goubin G (May 1993). "A human cDNA corresponding to a gene overexpressed during cell proliferation encodes a product sharing homology with amoebic and bacterial proteins". The Journal of Biological Chemistry. 268 (15): 11050–6. PMID8496166.
^Jin DY, Chae HZ, Rhee SG, Jeang KT (Dec 1997). "Regulatory role for a novel human thioredoxin peroxidase in NF-kappaB activation". The Journal of Biological Chemistry. 272 (49): 30952–61. doi:10.1074/jbc.272.49.30952. PMID9388242.
^Margarucci L, Monti MC, Tosco A, Esposito R, Zampella A, Sepe V, Mozzicafreddo M, Riccio R, Casapullo A (Jan 2015). "Theonellasterone, a steroidal metabolite isolated from a Theonella sponge, protects peroxiredoxin-1 from oxidative stress reactions". Chemical Communications. 51 (9): 1591–3. doi:10.1039/c4cc09205h. PMID25503482.
^El Eter E, Al-Masri AA (May 2015). "Peroxiredoxin isoforms are associated with cardiovascular risk factors in type 2 diabetes mellitus". Brazilian Journal of Medical and Biological Research. 48 (5): 465–9. doi:10.1590/1414-431X20144142. PMID25742636.
^ abMullen L, Hanschmann EM, Lillig CH, Herzenberg LA, Ghezzi P (2015). "Cysteine Oxidation Targets Peroxiredoxins 1 and 2 for Exosomal Release through a Novel Mechanism of Redox-Dependent Secretion". Molecular Medicine. 21: 98–108. doi:10.2119/molmed.2015.00033 (inactive 2015-04-02). PMID25715249.
^Cai CY, Zhai LL, Wu Y, Tang ZG (Feb 2015). "Expression and clinical value of peroxiredoxin-1 in patients with pancreatic cancer". European Journal of Surgical Oncology. 41 (2): 228–35. doi:10.1016/j.ejso.2014.11.037. PMID25434328.
^ abGong F, Hou G, Liu H, Zhang M (Feb 2015). "Peroxiredoxin 1 promotes tumorigenesis through regulating the activity of mTOR/p70S6K pathway in esophageal squamous cell carcinoma". Medical Oncology. 32 (2): 455. doi:10.1007/s12032-014-0455-0. PMID25579166.
Sauri H, Butterfield L, Kim A, Shau H (Mar 1995). "Antioxidant function of recombinant human natural killer enhancing factor". Biochemical and Biophysical Research Communications. 208 (3): 964–9. doi:10.1006/bbrc.1995.1428. PMID7702627.
Shau H, Butterfield LH, Chiu R, Kim A (1994). "Cloning and sequence analysis of candidate human natural killer-enhancing factor genes". Immunogenetics. 40 (2): 129–34. doi:10.1007/BF00188176. PMID8026862.
Kawai S, Takeshita S, Okazaki M, Kikuno R, Kudo A, Amann E (Apr 1994). "Cloning and characterization of OSF-3, a new member of the MER5 family, expressed in mouse osteoblastic cells". Journal of Biochemistry. 115 (4): 641–3. PMID8089076.
Shau H, Kim A (Feb 1994). "Identification of natural killer enhancing factor as a major antioxidant in human red blood cells". Biochemical and Biophysical Research Communications. 199 (1): 83–8. doi:10.1006/bbrc.1994.1197. PMID8123050.
Prospéri MT, Apiou F, Dutrillaux B, Goubin G (Jan 1994). "Organization and chromosomal assignment of two human PAG gene loci: PAGA encoding a functional gene and PAGB a processed pseudogene". Genomics. 19 (2): 236–41. doi:10.1006/geno.1994.1053. PMID8188254.
Jin DY, Chae HZ, Rhee SG, Jeang KT (Dec 1997). "Regulatory role for a novel human thioredoxin peroxidase in NF-kappaB activation". The Journal of Biological Chemistry. 272 (49): 30952–61. doi:10.1074/jbc.272.49.30952. PMID9388242.
Outinen PA, Sood SK, Pfeifer SI, Pamidi S, Podor TJ, Li J, Weitz JI, Austin RC (Aug 1999). "Homocysteine-induced endoplasmic reticulum stress and growth arrest leads to specific changes in gene expression in human vascular endothelial cells". Blood. 94 (3): 959–67. PMID10419887.
Yanagawa T, Ishikawa T, Ishii T, Tabuchi K, Iwasa S, Bannai S, Omura K, Suzuki H, Yoshida H (Oct 1999). "Peroxiredoxin I expression in human thyroid tumors". Cancer Letters. 145 (1-2): 127–32. doi:10.1016/S0304-3835(99)00243-8. PMID10530780.
Noh DY, Ahn SJ, Lee RA, Kim SW, Park IA, Chae HZ (2001). "Overexpression of peroxiredoxin in human breast cancer". Anticancer Research. 21 (3B): 2085–90. PMID11497302.
Kim SH, Fountoulakis M, Cairns N, Lubec G (2002). "Protein levels of human peroxiredoxin subtypes in brains of patients with Alzheimer's disease and Down syndrome". Journal of Neural Transmission. Supplementum (61): 223–35. doi:10.1007/978-3-7091-6262-0_18. PMID11771746.
Rabilloud T, Heller M, Gasnier F, Luche S, Rey C, Aebersold R, Benahmed M, Louisot P, Lunardi J (May 2002). "Proteomics analysis of cellular response to oxidative stress. Evidence for in vivo overoxidation of peroxiredoxins at their active site". The Journal of Biological Chemistry. 277 (22): 19396–401. doi:10.1074/jbc.M106585200. PMID11904290.
Chang TS, Jeong W, Choi SY, Yu S, Kang SW, Rhee SG (Jul 2002). "Regulation of peroxiredoxin I activity by Cdc2-mediated phosphorylation". The Journal of Biological Chemistry. 277 (28): 25370–6. doi:10.1074/jbc.M110432200. PMID11986303.
Yang KS, Kang SW, Woo HA, Hwang SC, Chae HZ, Kim K, Rhee SG (Oct 2002). "Inactivation of human peroxiredoxin I during catalysis as the result of the oxidation of the catalytic site cysteine to cysteine-sulfinic acid". The Journal of Biological Chemistry. 277 (41): 38029–36. doi:10.1074/jbc.M206626200. PMID12161445.
Geiben-Lynn R, Kursar M, Brown NV, Addo MM, Shau H, Lieberman J, Luster AD, Walker BD (Jan 2003). "HIV-1 antiviral activity of recombinant natural killer cell enhancing factors, NKEF-A and NKEF-B, members of the peroxiredoxin family". The Journal of Biological Chemistry. 278 (3): 1569–74. doi:10.1074/jbc.M209964200. PMID12421812.