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Homocysteine modulates Gq11, G12/13, Gi/o G protein expression independent of protease activated receptor (PAR)
Author(s) -
Vacek Thomas Paul,
Tyagi Neetu,
Sen Utpal,
Moshal Karni,
Passmore John,
Kumar Munish,
Steed Mesia,
Tyagi Suresh
Publication year - 2008
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.22.1_supplement.1155.21
Subject(s) - receptor , protease activated receptor 2 , g protein coupled receptor , microbiology and biotechnology , agonist , protease activated receptor , chemistry , g protein , liver x receptor alpha , 5 ht5a receptor , biology , transcription factor , biochemistry , thrombin , gene , immunology , platelet , nuclear receptor
Homocysteine (Hcy) indirectly activates protease‐activated receptors (PARs). PARs belong to the G protein‐coupled receptor family (GPCR) that utilizes Gq/11, G12/13 and Gi/o. Differential expression of these G proteins is involved in cardiac hypertrophy. Since agonist binding to PARs induces desensitization and sequestration of the PAR receptors, we hypothesize that the intracellular G protein content will be modulated in relation to PAR receptor. Microvascular endothelial cells (MVECs) were treated with varying concentrations of Hcy 0–100μM for 0–48 h. RT‐PCR was used to determine transcription levels of PAR receptors. Expression of the four PAR receptors and their G proteins, Gq/11, G12/13, Gi/o, was determined with Western blot analysis. We report that PAR‐2 and PAR‐3 transcription decreased, while PAR‐4 transcription levels increased in a time and concentration‐dependent manner. G q/11 G protein content decreased at 24h. G12/13 and Gi/o expression was decreased at 48h with higher Hcy concentration. However, protein expression levels of all PAR receptors remained the same at 24 h and 48 h. Confocal analysis confirmed differential expression of Gq/11,G12/13 and Gi/o. The results suggest that differential G protein expression is not attributed to PAR receptor modulation. This suggests that Hcy modulates the down‐regulation of other GPCRs that utilize these G proteins.