手术中含有脯氨酰羟化酶结构域的酶的治疗抑制:推测的应用和挑战

J. Harnoss, Moritz J. Strowitzki, P. Radhakrishnan, L. K. Platzer, J. Harnoss, T. Hank, Jun Cai, A. Ulrich, Martin Schneider
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引用次数: 26

摘要

氧气是后生动物产生能量所必需的。缺氧时,缺氧诱导因子(hif)和脯氨酰羟化酶结构域酶(PHDs)介导的适应性和保护性途径被诱导。两者都在与长时间缺血和炎症相关的各种疾病中发挥关键作用,并且是治疗干预的有希望的靶点。本文综述了在外科相关疾病如肝脏和肠道疾病、伤口愈合、先天免疫反应和肿瘤发生等方面的治疗性PHD调节,并讨论了PHD抑制在外科患者中的治疗潜力和挑战。
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Therapeutic inhibition of prolyl hydroxylase domain-containing enzymes in surgery: putative applications and challenges
Oxygen is essential for metazoans to generate energy. Upon oxygen deprivation adaptive and protective pathways are induced, mediated by hypoxia-inducible factors (HIFs) and prolyl hydroxylase domain-containing enzymes (PHDs). Both play a pivotal role in various conditions associated with prolonged ischemia and inflammation, and are promising targets for therapeutic intervention. This review focuses on aspects of therapeutic PHD modulation in surgically relevant disease conditions such as hepatic and intestinal disorders, wound healing, innate immune responses, and tumorigenesis, and discusses the therapeutic potential and challenges of PHD inhibition in surgical patients.
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Abstract IA-015: Hypoxia-induced SETX links replication stress with the unfolded protein response Abstract PO-033: Papaverine derivative smv-32 alleviates tumor hypoxia and radiosensitizes tumors by inhibiting mitochondrial metabolism Abstract PO-034: Changes in cancer associated fibroblast subsets following angiotensin II type I receptor blocker (ARB) treatment reduces transient hypoxia and radiation resistance Abstract IA-017: Chromatin and gene transcription in hypoxia Abstract IA-016: Metabolic deregulation drives a redox vulnerability in pancreatic cancer
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