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Role of the G-protein and tyrosine kinase--Rho/ROK pathways in 15-hydroxyeicosatetraenoic acid induced pulmonary vasoconstriction in hypoxic rats.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Wang, Yali Liang, Di Wang, S. B. T. Qiu, Zhaoping Chu, Xiaojie Chen, Shuo Li, Lisha Chen, Lianlian Zhang, Rong Wang, Zhigang Zhu, Daling |
| Copyright Year | 2010 |
| Abstract | It has been previously reported by us that hypoxia activates lung 15-lipoxygenase (15-LO), which catalyzes arachidonic acid to 15-hydroxyeicosatetraenoic acid (15-HETE), leading to the constriction of pulmonary artery (PA). Rho-associated serine/threonine kinase (ROK), a downstream effector of small GTPase RhoA that may be modulated by G-protein and tyrosine kinase, plays an important role in smooth muscle contraction. However, whether the 15-HETE induced PA vasoconstriction involves the Rho/ROK pathway remains to be demonstrated. Therefore, we studied the contribution of ROK as well as G-protein and tyrosine kinase to the 15-HETE induced pulmonary vasoconstriction using PA ring technique, RNA interference technology, RP-HPLC, western blot and RT-PCR combined with the blockers. The hypoxia-induced expression of ROK is regulated by 15-HETE in rat PA smooth muscle cells (PASMCs), leading to vasoconstriction. The up-regulation of ROK expression caused by 15-HETE appears to be mediated by the G-protein and tyrosine kinase pathways. The translocation of ROK2 from the nucleus to the cytoplasm during hypoxia exposure relies on the mechanism for 15-HETE production. These results suggest that 15-HETE may mediate the up-regulation of ROK expression through G-protein and tyrosine kinase pathways under hypoxic condition, leading to PA vasoconstriction. |
| Starting Page | 96 |
| Ending Page | 102 |
| Page Count | 7 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://beyotime.com/reference/s1628-ref1.pdf |
| PubMed reference number | 20139061v1 |
| Alternate Webpage(s) | https://doi.org/10.1093/jb/mvq010 |
| DOI | 10.1093/jb/mvq010 |
| Journal | Journal of biochemistry |
| Volume Number | 147 |
| Issue Number | 5 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Arachidonate 15-Lipoxygenase Arachidonic Acid Cell Nucleus Hypoxia MARK2 gene Muscle Cells Myocytes, Smooth Muscle Protein Tyrosine Kinase Protein-Serine-Threonine Kinases Pulmonary artery structure RNA Interference Smooth muscle (tissue) Structure of parenchyma of lung Thioctic Acid Threonine Up-Regulation (Physiology) Vascular constriction (function) Western Blotting smooth muscle contraction |
| Content Type | Text |
| Resource Type | Article |