title: Acute stressor exposure modifies plasma exosome-associated heat shock protein 72 (Hsp72) and microRNA (miR-142-5p and miR-203).
abstract: Exosomes, biologically active nanoparticles (40-100 nm) released by hematopoietic and non-hematopoietic cells, contain a variety of proteins and small, non-coding RNA known as microRNA (miRNA). Exposure to various pathogens and disease states modifies the composition and function of exosomes, but there are no studies examining in vivo exosomal changes evoked by the acute stress response. The present study reveals that exposing male Fisher 344 rats to an acute stressor modulates the protein and miRNA profile of circulating plasma exosomes, specifically increasing surface heat shock protein 72 (Hsp72) and decreasing miR-142-5p and -203. The selected miRNAs and Hsp72 are associated with immunomodulatory functions and are likely a critical component of stress-evoked modulation of immunity. Further, we demonstrate that some of these stress-induced modifications in plasma exosomes are mediated by sympathetic nervous system (SNS) activation of alpha-1 adrenergic receptors (ADRs), since drug-mediated blockade of the receptors significantly attenuates the stress-induced modifications of exosomal Hsp72 and miR-142-5p. Together, these findings demonstrate that activation of the acute stress response modifies the proteomic and miRNA profile of exosomes released into the circulation.
authors.affiliation: Department of Integrative Physiology and the Center for Neuroscience, University of Colorado at Boulder, Boulder, Colorado, United States of America.
authors.forename: Lida A
authors.initials: LA
authors.lastname: Beninson
authors.affiliation: Department of Chemistry and Biochemistry and the BioFrontiers Institute, University of Colorado at Boulder, Boulder, Colorado, United States of America.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Brown
authors.affiliation: Department of Integrative Physiology and the Center for Neuroscience, University of Colorado at Boulder, Boulder, Colorado, United States of America.
authors.forename: Alice B
authors.initials: AB
authors.lastname: Loughridge
authors.affiliation: Department of Chemistry, Washington State University, Pullman, Washington, United States of America.
authors.forename: Jonel P
authors.initials: JP
authors.lastname: Saludes
authors.affiliation: Department of Integrative Physiology and the Center for Neuroscience, University of Colorado at Boulder, Boulder, Colorado, United States of America.
authors.forename: Thomas
authors.initials: T
authors.lastname: Maslanik
authors.affiliation: Department of Integrative Physiology and the Center for Neuroscience, University of Colorado at Boulder, Boulder, Colorado, United States of America.
authors.forename: Abigail K
authors.initials: AK
authors.lastname: Hills
authors.affiliation: Department of Integrative Physiology and the Center for Neuroscience, University of Colorado at Boulder, Boulder, Colorado, United States of America.
authors.forename: Tyler
authors.initials: T
authors.lastname: Woodworth
authors.affiliation: Department of Integrative Physiology and the Center for Neuroscience, University of Colorado at Boulder, Boulder, Colorado, United States of America.
authors.forename: Wendy
authors.initials: W
authors.lastname: Craig
authors.affiliation: Department of Chemistry and Biochemistry and the BioFrontiers Institute, University of Colorado at Boulder, Boulder, Colorado, United States of America; Center of Basic Molecular Science, Department of Chemistry, Tsinghua University, Beijing, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Yin
authors.affiliation: Department of Integrative Physiology and the Center for Neuroscience, University of Colorado at Boulder, Boulder, Colorado, United States of America.
authors.forename: Monika
authors.initials: M
authors.lastname: Fleshner
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004597:Electroshock; D055354:Exosomes / Q000378:metabolism*; D050884:HSP72 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D013312:Stress, Physiological / Q000502:physiology*; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000378:metabolism
chemical_list: D016207:Cytokines; D050884:HSP72 Heat-Shock Proteins; C583884:MIRN142 microRNA, rat; C000604042:MIRN203 microRNA, rat; D035683:MicroRNAs; D018340:Receptors, Adrenergic, alpha-1