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Systematic Hypoxia Mediates Platelet‐induced Hypoxia Inducible Factor‐1 Expression in Polymorphonuclear Leukocyte in Men
Author(s) -
Liu Huang Chun,
Wang Jong Shyan
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1286-c
Subject(s) - platelet , hypoxia (environmental) , ubiquitin , chemistry , inflammation , hypoxia inducible factors , endocrinology , basal (medicine) , medicine , platelet activation , biology , biochemistry , oxygen , organic chemistry , gene , insulin
Platelet and polymorphonuclear leukocyte (PMN) co‐localization to the damaged vessel is an essential component of a multi‐step cascade in thrombosis and inflammation. Hypoxia‐inducible factor‐1 (HIF‐1) regulates several important PMN functions relevant to innate immune and inflammation during hypoxia. Hydroxylation and ubiquitination regarding HIF‐1α‐ von Hippel‐Lindau tumor suppressor protein (vHL) ‐ubiquitin interactions contribute to cellular HIF‐1 stabilization and bioavailability. Therefore, this study was to investigate how platelet affects HIF‐1α bioavailability of PMN and its role in PMN‐mediated inflammatory responses under various hypoxic conditions. Twelve healthy sedentary men were exposed to 12% (severe hypoxia, SH), 15% (moderate hypoxia, MH), and 18% (light hypoxia, LH) O 2 for 2 hours in a normobaric hypoxia chamber. In normxic condition, platelets enhanced nucleus HIF‐1α level in PMNs, whereas N‐acetylcysteine, an antioxidant, attenuated the platelet‐promoted HIF‐1α translocation of PMNs; 2) SH enhanced basal nuclear HIF‐1α content but suppressed platelet‐promoted HIF‐1α translocation of PMNs, whereas basal and platelet‐mediated HIF‐1α expressions were unchanged in response to MH and LH; and 3) platelets decreased both vHL and ubiquitin contents in PMNs at a noximic condition, whereas SH, but not MH and LH, enhanced basal vHL content and decreased basal ubiquitin content in PMNs as well as promoted extents of PMN vHL and ubiquitin suppressed by platelets. We conclude that SH enhances nuclear HIF‐1α content in PMN and down‐regulates platelet‐promoted HIF‐1α translocation of PMNs, possible by modulating interactions between HIF‐1α, vHL, and ubiquitin. However, both MH and LH did not influence this response mediated by HIF‐1.