期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
卷 1843, 期 11, 页码 2528-2542出版社
ELSEVIER
DOI: 10.1016/j.bbamcr.2014.06.012
关键词
Endothelial; Circulating microRNA; Hypoxia; Hypoxamir; Mitochondrial metabolism
资金
- NIH [KO8, HL RO1 079647, RO1 HL0055454, HL085446]
- Lerner Fund
- Harris Fund
- Watkins Fund
- Gilead Research Scholars Fund
- Pulmonary Hypertension Association
Complex organisms may coordinate molecular responses to hypoxia by specialized avenues of communication across multiple tissues, but these mechanisms are poorly understood. Plasma-based, extracellular microRNAs have been described, yet their regulation and biological functions in hypoxia remain enigmatic. We found a unique pattern of release of the hypoxia-inducible microRNA-210 (miR-210) from hypoxic and reoxygenated cells. This microRNA is also elevated in human plasma in physiologic and pathologic conditions of altered oxygen demand and delivery. Released miR-210 can be delivered to recipient cells, and the suppression of its direct target ISCU and mitochondrial metabolism is primarily evident in hypoxia. To regulate these hypoxia-specific actions, prolyl-hydroxylation of Argonaute 2 acts as a molecular switch that reciprocally modulates miR-210 release and intracellular activity in source cells as well as regulates intracellular activity in recipient cells after miR-210 delivery. Therefore, Argonaute 2-dependent control of released miR-210 represents a unique communication system that integrates the hypoxic response across anatomically distinct cells, preventing unnecessary activity of delivered miR-210 in normoxia while still preparing recipient tissues for incipient hypoxic stress and accelerating adaptation. (C) 2014 The Authors. Published by Elsevier B.V.
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