The transcriptional response to hypoxia is temporally regulated, yet the molecular underpinnings and physiological implications are unknown. We examined the roles of hepatic Bmal1 and Hif1α in the circadian response to hypoxia in mice. We found that the majority of the transcriptional response to hypoxia is dependent on either Bmal1 or Hif1α, through shared and distinct roles that are daytime determined.
View Article and Find Full Text PDFIn mammals, O2 and CO2 levels are tightly regulated and are altered under various pathological conditions. While the molecular mechanisms that participate in O2 sensing are well characterized, little is known regarding the signaling pathways that participate in CO2 signaling and adaptation. Here, we show that CO2 levels control a distinct cellular transcriptional response that differs from mere pH changes.
View Article and Find Full Text PDFMany cell types secrete spherical membrane bodies classified as extracellular vesicles (EVs). EVs participate in intercellular communication and are present in body fluids, including blood, lymph, and cerebrospinal fluid. The time of EVs survival in the body varies depending on the body's localisation.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2022
High altitude exposes humans to hypobaric hypoxia, which induces various physiological and molecular changes. Recent studies point toward interaction between circadian rhythms and the hypoxic response, yet their human relevance is lacking. Here, we examine the effect of different high altitudes in conjunction with time of day on human whole-blood transcriptome upon an expedition to the highest city in the world, La Rinconada, Peru, which is 5,100 m above sea level.
View Article and Find Full Text PDF