{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T12:53:32Z","timestamp":1783947212592,"version":"3.55.0"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pulmonary vasoconstriction resulting from intermittent hypoxia (IH) contributes to pulmonary hypertension (pHTN) in patients with sleep apnea (SA), although the mechanisms involved remain poorly understood. Based on prior studies in patients with SA and animal models of SA, the objective of this study was to evaluate the role of PKC\u03b2 and mitochondrial reactive oxygen species (mitoROS) in mediating enhanced pulmonary vasoconstrictor reactivity after IH. We hypothesized that PKC\u03b2 mediates vasoconstriction through interaction with the scaffolding protein PICK1 (protein interacting with C kinase 1), activation of mitochondrial ATP-sensitive potassium channels (mitoKATP), and stimulated production of mitoROS. We further hypothesized that this signaling axis mediates enhanced vasoconstriction and pHTN after IH. Rats were exposed to IH or sham conditions (7 h\/d, 4 wk). Chronic oral administration of the antioxidant Tempol or the PKC\u03b2 inhibitor LY-333531 abolished IH-induced increases in right ventricular systolic pressure and right ventricular hypertrophy. Furthermore, scavengers of O2 \u00a0\u2212 or mitoROS prevented enhanced PKC\u03b2-dependent vasoconstrictor reactivity to endothelin-1 in pulmonary arteries from IH rats. In addition, this PKC\u03b2\/mitoROS signaling pathway could be stimulated by the PKC activator PMA in pulmonary arteries from control rats, and in both rat and human pulmonary arterial smooth muscle cells. These responses to PMA were attenuated by inhibition of mitoKATP or PICK1. Subcellular fractionation and proximity ligation assays further demonstrated that PKC\u03b2 acutely translocates to mitochondria upon stimulation and associates with PICK1. We conclude that a PKC\u03b2\/mitoROS signaling axis contributes to enhanced vasoconstriction and pHTN after IH. Furthermore, PKC\u03b2 mediates pulmonary vasoconstriction through interaction with PICK1, activation of mitoKATP, and subsequent mitoROS generation.<\/jats:p>","DOI":"10.1165\/rcmb.2019-0351oc","type":"journal-article","created":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T10:09:37Z","timestamp":1581502177000},"page":"732-746","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":27,"title":["Intermittent Hypoxia Augments Pulmonary Vasoconstrictor Reactivity through PKC\u03b2\/Mitochondrial Oxidant Signaling"],"prefix":"10.1093","volume":"62","author":[{"given":"Jessica B.","family":"Snow","sequence":"first","affiliation":[{"name":"Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles E.","family":"Norton","sequence":"additional","affiliation":[{"name":"Vascular 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