气候变化领域集成服务门户(CCPortal): Circulating levels of hydroxylated bradykinin function as an indicator of tissue HIF-1α expression

CCPortal

DOI	10.1016/j.scib.2020.04.023
	Circulating levels of hydroxylated bradykinin function as an indicator of tissue HIF-1α expression
	Liu Y.; Gu Y.; Ng S.; Deng Z.; Lyon C.J.; Koay E.J.; Ning B.; Katz M.H.; Chiao P.J.; Fan J.; Han H.; Von Hoff D.; Hu T.Y.
发表日期	2020
ISSN	20959273
起始页码	1570
结束页码	1579
卷号	65 期号:18
英文摘要	The critical roles of oxygen homeostasis in metabolism are indisputable and hypoxic responses are correlated with the pathogenesis of gastrointestinal, pulmonary, renal diseases and cancers. Evaluating tissue hypoxia to predict treatment outcome is challenging, however, due to the lack of rapid, accurate and non-invasive methods. Hypoxia enhances prolyl-4-hydroxylase α1 (P4HA1) expression, which can convert bradykinin (BK) to hydroxyprolyl-BK (Hyp-BK), leading us to hypothesize that circulating Hyp-BK/BK ratios may reflect tissue hypoxia and predict treatment outcomes. Direct quantification of Hyp-BK peptides in serum or plasma by conventional MALDI-TOF MS analysis is technically challenging. In our study, a nanopore-based fractionation and enrichment protocol was utilized to allow the simple workflow for circulating Hyp-BK/BK analysis. Hypoxia is linked to poor prognosis due to its role in promoting pancreatic cancer progression and metastasis. Here we show that P4HA1 expression was increased in pancreatic tumors versus adjacent tissue, associated with poor survival, and corresponded with tumor expression of the hypoxia inducible factor 1α (HIF-1α) and carbonic anhydrase 9 (CA9). Hypoxia-induced P4HA1 expression and BK conversion to Hyp-BK were found to be HIF-1α dependent, pre-treatment serum Hyp-BK/BK ratios corresponded with tissue HIF-1α and P4HA1 expression, and high Hyp-BK/BK levels corresponded with poor response to therapy. These results suggest that pre-treatment circulating Hyp-BK/BK ratios may have value as a non-invasive, surrogate indicator of tissue hypoxia and tumor responses to therapy. © 2020 Science China Press
关键词	Circulating indicator HIF-1α Hydroxyprolyl bradykinin Hypoxia P4HA1
英文关键词	Carbonic anhydrase; Diseases; Noninvasive medical procedures; Tumors; Hypoxia inducible factor 1-alpha; MALDI-TOF-MS analysis; Noninvasive methods; Pancreatic cancers; Pancreatic tumors; Prolyl-4-hydroxylase; Surrogate indicators; Treatment outcomes; Diagnosis
语种	英语
来源期刊	Science Bulletin
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/207135
作者单位	Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112, United States; Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, United States; Molecular Medicine Division, Translational Genomics Research Institute, Phoenix, AZ 85004, United States; Division of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, United States; Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States; Department of Molecular and Cellular Oncology, Division of Basic Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
推荐引用方式 GB/T 7714	Liu Y.,Gu Y.,Ng S.,et al. Circulating levels of hydroxylated bradykinin function as an indicator of tissue HIF-1α expression[J],2020,65(18).
APA	Liu Y..,Gu Y..,Ng S..,Deng Z..,Lyon C.J..,...&Hu T.Y..(2020).Circulating levels of hydroxylated bradykinin function as an indicator of tissue HIF-1α expression.Science Bulletin,65(18).
MLA	Liu Y.,et al."Circulating levels of hydroxylated bradykinin function as an indicator of tissue HIF-1α expression".Science Bulletin 65.18(2020).