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HIF-1α-l-PGDS-PPARγ regulates hypoxia-induced ANP secretion in beating rat atria
- Source :
- Prostaglandinsother lipid mediators. 134
- Publication Year :
- 2017
-
Abstract
- Lipocalin-type prostaglandin D synthase (L-PGDS) and peroxisome proliferator activated receptor γ (PPARγ) play important roles in cardiovascular diseases. Nevertheless, effects of hypoxia-inducible factor 1α (HIF-1α) on L-PGDS and PPARγ protein levels and its role in hypoxia-induced atrial natriuretic peptide (ANP) secretion are unclear. In perfused beating rat atria, we observed that hypoxia significantly increased HIF-1α protein levels and stimulated ANP secretion, while upregulating L-PGDS. Hypoxia-induced ANP secretion was clearly attenuated by HIF-1α antagonist 2-methoxyestradiol, downregulating both HIF-1α and L-PGDS protein levels. It was also attenuated by L-PGDS antagonists, AT-56 and HQL-49, downregulating L-PGDS protein levels. In addition, hypoxia-induced ANP secretion was accompanied by increased PPARγ protein levels and was strongly attenuated by PPARγ antagonist GW9662. Hypoxia-induced increase in atrial PPARγ protein levels were dramatically inhibited by both 2-methoxyestradiol and AT-56. These results indicated that hypoxia promotes ANP secretion, at least in part, by activating HIF-1α-l-PGDS-PPARγ signaling in beating rat atria.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_specialty
Physiology
Peroxisome proliferator-activated receptor
Biochemistry
Prostaglandin-D synthase
03 medical and health sciences
Atrial natriuretic peptide
Internal medicine
medicine
Lipocalin-type prostaglandin D synthase
Animals
Secretion
Heart Atria
Rat atria
Pharmacology
chemistry.chemical_classification
biology
Antagonist
Cell Biology
Hypoxia (medical)
Atrial Function
Hypoxia-Inducible Factor 1, alpha Subunit
Cell Hypoxia
Lipocalins
Rats
Intramolecular Oxidoreductases
PPAR gamma
030104 developmental biology
Endocrinology
chemistry
Gene Expression Regulation
cardiovascular system
biology.protein
Female
medicine.symptom
Atrial Natriuretic Factor
Subjects
Details
- ISSN :
- 10988823
- Volume :
- 134
- Database :
- OpenAIRE
- Journal :
- Prostaglandinsother lipid mediators
- Accession number :
- edsair.doi.dedup.....5a153fc9ea40ac6f3c720b43ba0c75f9