Maintenance of cellular redox control is pivotal for normal cellular functions and cell fate decisions including cell death. Among the key cellular redox systems in mammals, the glutathione peroxidase (GPX) family of proteins is the largest conferring multifaceted functions and affecting virtually all cellular processes. The endoplasmic reticulum (ER)- resident glutathione peroxidases, designated as GPX7 and GPX8, are the most recently added members of this family of enzymes. Recent studies have provided exciting insights how both enzymes support critical processes of the ER including oxidative protein folding, maintenance of ER redox control, by eliminating H2O2, and preventing palmitic acid-induced lipotoxicity. Consequently, numerous pathological conditions, such as neurodegeneration, cancer and metabolic diseases have been linked with altered GPX7 and GPX8 expression. Studies in mice have demonstrated that loss of GPX7 leads to increased differentiation of preadipocytes, increased tumorigenesis and shortened lifespan. By contrast, GPX8 deficiency in mice results in enhanced caspase-4/11 activation and increased endotoxic shock in colitis model. With the increasing recognition that both types of enzymes are dysregulated in various tumor entities in man, we deem a review of the emerging roles played by GPX7 and GPX8 in health and disease development timely and appropriate.

中文翻译：

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不含硒的内质网驻留谷胱甘肽过氧化物酶在细胞信号传导和疾病中的新作用

维持细胞氧化还原控制对于正常细胞功能和细胞命运决定（包括细胞死亡）至关重要。在哺乳动物的关键细胞氧化还原系统中，谷胱甘肽过氧化物酶 (GPX) 蛋白质家族是最大的赋予多方面功能并影响几乎所有细胞过程。内质网 (ER) 驻留型谷胱甘肽过氧化物酶，指定为 GPX7 和 GPX8，是该酶家族中最新添加的成员。最近的研究提供了令人兴奋的见解，这两种酶如何通过消除 H2O2 和防止棕榈酸诱导的脂毒性来支持 ER 的关键过程，包括氧化蛋白质折叠、维持 ER 氧化还原控制。因此，许多病理状况，例如神经变性，癌症和代谢疾病与 GPX7 和 GPX8 表达的改变有关。对小鼠的研究表明，GPX7 的缺失会导致前脂肪细胞分化增加、肿瘤发生增加和寿命缩短。相比之下，小鼠 GPX8 缺乏导致结肠炎模型中 caspase-4/11 激活增强和内毒素休克增加。随着人们越来越认识到这两种酶在人类各种肿瘤实体中失调，我们认为对 GPX7 和 GPX8 在健康和疾病发展中发挥的新兴作用进行及时和适当的审查。小鼠 GPX8 缺乏导致结肠炎模型中 caspase-4/11 活化增强和内毒素休克增加。随着人们越来越认识到这两种酶在人类各种肿瘤实体中失调，我们认为对 GPX7 和 GPX8 在健康和疾病发展中发挥的新兴作用进行及时和适当的审查。小鼠 GPX8 缺乏导致结肠炎模型中 caspase-4/11 活化增强和内毒素休克增加。随着人们越来越认识到这两种酶在人类各种肿瘤实体中失调，我们认为对 GPX7 和 GPX8 在健康和疾病发展中发挥的新兴作用进行及时和适当的审查。