title: Effects of intermittent hypoxia on leptin signalling in the carotid body.
abstract: Glomus cells in the carotid body are responsible for detecting changes in the partial pressure of blood oxygen (PO₂). These glomus cells have recently been found to express leptin receptors and are activated by intermittent hypoxia (IH) and systemic leptin injections, although the function of leptin within the carotid body remains unknown. The present study was done to investigate whether IH activates leptin signalling pathways within leptin-expressing carotid body glomus cells. Rats were subjected to IH (120-s normoxia, 80-s hypoxia for 8 h) or normoxia (8 h). Exposure to IH increased plasma leptin levels almost sixfold compared to normoxic controls. Additionally, IH was found to increase leptin, ERK1/2 and Fra-1/2 immunoreactivity within glomus cells. Systemic leptin injections evoked similar effects on leptin, ERK1/2 and Fra-1/2 immunoreactivity within the glomus cells. Furthermore, using Western blot analysis, IH was found to increase protein expression of leptin, the short form of the leptin receptor (Ob-R₁₀₀ kDa) and suppressor of cytokine signalling 3. On the other hand, IH induced a decrease in long form of leptin receptors (Ob-Rb) protein expression. Taken together, these data suggest that the increased levels of leptin within the circulation and those within the glomus cells induced by IH may alter carotid bodies chemosensitivity to hypoxic stimuli.
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada N6A 5C1.
authors.forename: S A
authors.initials: SA
authors.lastname: Messenger
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada N6A 5C1. Electronic address: john.ciriello@schulich.uwo.ca.
authors.forename: J
authors.initials: J
authors.lastname: Ciriello
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002344:Carotid Body / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D051921:Fos-Related Antigen-2 / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D054411:Receptors, Leptin / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D000099169:Fos-Related Antigen 1
chemical_list: D051921:Fos-Related Antigen-2; D020738:Leptin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D016760:Proto-Oncogene Proteins c-fos; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D000099169:Fos-Related Antigen 1; C497874:Fosl2 protein, rat; C491410:Socs3 protein, rat; C494088:Stat3 protein, rat