Fujii Junichi, Ikeda Yoshitaka, Kurahashi Toshihiro, Homma Takujiro
Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, 2-2-2 Iidanishi, Yamagata 990-9585, Japan.
Division of Molecular Cell Biology, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan.
Free Radic Biol Med. 2015 Jun;83:373-9. doi: 10.1016/j.freeradbiomed.2015.01.025. Epub 2015 Feb 2.
Peroxiredoxins (PRDXs) form an enzyme family that exhibits peroxidase activity using electrons from thioredoxin and other donor molecules. As the signaling roles of hydrogen peroxide in response to extracellular stimuli have emerged, the involvement of PRDX in the hydrogen peroxide-mediated signaling has become evident. Among six PRDX members in mammalian cells, PRDX4 uniquely possesses a hydrophobic signal peptide at the amino terminus, and, hence, it undergoes either secretion or retention by the endoplasmic reticulum (ER) lumen. The role of PRDX4 as a sulfoxidase in ER is now attracting much attention regarding the oxidative protein folding of nascent proteins. Contrary to this role in the ER, the functional significance of PRDX4 in the extracellular milieu is virtually unknown despite its implications as a biomarker under pathological conditions in some diseases. Other than its systemically expressed form, a variant form of PRDX4 is transcribed from the upstream promoter/exon 1 of the systemic promoter/exon 1 and is uniquely expressed in sexually matured testes. Circumstantial evidence, together with deduced functions from the systemic form, suggests that there are potential roles for testicular PRDX4 in the reproductive processes such as the regulation of hormonal signals and the oxidative packaging of sperm chromatin. Elucidation of these PRDX4 functions under in vivo situations is expected to show the whole picture of how PRDX4 has evolved in multicellular organisms.
过氧化物酶（PRDXs）构成一个酶家族，该家族利用来自硫氧还蛋白和其他供体分子的电子表现出过氧化物酶活性。随着过氧化氢在响应细胞外刺激时的信号传导作用逐渐显现，PRDX参与过氧化氢介导的信号传导也变得明显起来。在哺乳动物细胞的六个PRDX成员中，PRDX4在氨基末端独特地拥有一个疏水信号肽，因此，它会被内质网（ER）腔分泌或保留。PRDX4作为内质网中的亚砜氧化酶在新生蛋白质的氧化蛋白折叠方面的作用目前备受关注。与它在内质网中的这个作用相反，尽管PRDX4在某些疾病的病理条件下作为生物标志物有一定意义，但其在细胞外环境中的功能意义实际上还不清楚。除了其全身表达形式外，PRDX4的一种变体形式是从全身启动子/外显子1的上游启动子/外显子1转录而来，并且在性成熟的睾丸中独特表达。间接证据以及从全身形式推导的功能表明，睾丸PRDX4在生殖过程中可能发挥作用，如调节激素信号和精子染色质的氧化包装。对这些PRDX4在体内情况下功能的阐明有望展现PRDX4在多细胞生物中是如何进化的全貌。
