Division of Cellular and Molecular Cerebral Ischemia, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Exp Gerontol. 2010 Mar;45(3):217-34. doi: 10.1016/j.exger.2010.01.004. Epub 2010 Jan 11.
Oxidative stress significantly impacts multiple cellular pathways that can lead to the initiation and progression of varied disorders throughout the body. It therefore becomes imperative to elucidate the components and function of novel therapeutic strategies against oxidative stress to further clinical diagnosis and care. In particular, both the growth factor and cytokine erythropoietin (EPO) and members of the mammalian forkhead transcription factors of the O class (FoxOs) may offer the greatest promise for new treatment regimens since these agents and the cellular pathways they oversee cover a range of critical functions that directly influence progenitor cell development, cell survival and degeneration, metabolism, immune function, and cancer cell invasion. Furthermore, both EPO and FoxOs function not only as therapeutic targets, but also as biomarkers of disease onset and progression, since their cellular pathways are closely linked and overlap with several unique signal transduction pathways. However, biological outcome with EPO and FoxOs may sometimes be both unexpected and undesirable that can raise caution for these agents and warrant further investigations. Here we present the exciting as well as complicated role EPO and FoxOs possess to uncover the benefits as well as the risks of these agents for cell biology and clinical care in processes that range from stem cell development to uncontrolled cellular proliferation.
氧化应激显著影响多种细胞途径,这些途径可能导致全身各种疾病的发生和发展。因此,阐明针对氧化应激的新型治疗策略的组成和功能对于进一步的临床诊断和护理至关重要。特别是生长因子和细胞因子促红细胞生成素(EPO)以及哺乳动物叉头转录因子 O 类(FoxOs)的成员,由于这些药物及其监管的细胞途径涵盖了一系列直接影响祖细胞发育、细胞存活和退化、代谢、免疫功能和癌细胞侵袭的关键功能,因此可能为新的治疗方案提供最大的希望。此外,EPO 和 FoxOs 的功能不仅可以作为治疗靶点,还可以作为疾病发生和进展的生物标志物,因为它们的细胞途径密切相关且与几个独特的信号转导途径重叠。然而,EPO 和 FoxOs 的生物学结果有时可能是出乎意料和不可取的,这可能会对这些药物产生警惕,并需要进一步的研究。在这里,我们展示了 EPO 和 FoxOs 所具有的令人兴奋但又复杂的作用,以揭示这些药物在从干细胞发育到不受控制的细胞增殖的过程中对细胞生物学和临床护理的益处和风险。