Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.11.2 (prolyl hydroxylase)
 1,814 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular smooth muscle cells (V-SMC) alter their functions from contraction to production of extracellular matrices during the response to injury of the arterial wall. Accumulation of these matrices characterize the chronic structural change of arteriosclerosis. In this paper, we reported as follows. (1) V-SMC freshly isolated from human aortic media had strong reactivity with anti-smooth muscle specific alpha-actin (alpha-SM actin) antibody but not with anti-prolyl 4-hydroxylase (ProHy) antibody. (2) The exponentially growing cells in serum-containing culture media reduced alpha-SM actin and induced ProHy distinctly. (3) Growth-arrested cells with serum starvation rearranged numerous alpha-SM actin fibers in their cytoplasm. And the rearrangement of contractile filaments inhibited by the addition of single competence growth factor, such as platelet derived growth factor (PDGF) or basic fibroblast growth factor (bFGF). These results suggest that V-SMC change their phenotype in a competence-factor-dependent manner.
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PMID:Competence growth factors evoke the phenotypic transition of arterial smooth muscle cells. 217 12

SM-20 encodes an intracellular prolyl hydroxylase that acts on hypoxia inducible factor (HIF)-1alpha, targeting it for proteasomal degradation. By decreasing HIF-alpha, SM-20 is thought to modulate the expression of hypoxia-regulated genes. SM-20 expression in the arterial wall is restricted to smooth muscle cells, which play a critical role in atherosclerosis and arterial injury. To further elucidate the regulation of SM-20 in smooth muscle, we cloned and analyzed the rat SM-20 promoter. In transient transfections, the SM-20 promoter displayed approximately 6-fold greater activity in smooth muscle cells vs. fibroblasts. Deletion analysis and electrophoretic mobility shift assays demonstrated that SM-20 transcription was regulated by two Sp1/Sp3 sites. A shift in binding to the Sp1/Sp3 sites, a decrease in Sp1 and Sp3 protein levels, and the emergence of a lower molecular weight form of Sp1 were seen in serum-deprived or post-confluent SMC, suggesting that SM-20 is regulated during smooth muscle cell differentiation.
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PMID:Regulation of the SM-20 prolyl hydroxylase gene in smooth muscle cells. 1508 11

Arterial O(2) levels are thought to modulate vascular smooth muscle cell (VSMC) proliferation and vascular remodeling, but the mechanisms involved are poorly understood. Here, we tested the hypothesis that PHD2, a prolyl hydroxylase domain (PHD)-containing O(2) sensor, modulates growth factor-induced proliferative responses of human pulmonary artery SMC (HPASMC). We found that both PHD1 and PHD2 were robustly expressed by HPASMC, and inhibiting prolyl hydroxylase activity pharmacologically by using the nonselective dioxygenase inhibitor dimethyloxalylglycine (DMOG) inhibited proliferation and cyclin A expression induced by PDGF-AB or FGF-2. Specific knockdown of PHD2 using small interfering RNAs had similar effects. The inhibitory effects of DMOG and PHD2 knockdown on proliferation and cyclin A expression were seen under both normoxic (20% O(2)) and moderately hypoxic (5% O(2)) conditions, and PHD2 expression was not affected by O(2) level nor by stimulation with PDGF or FGF-2, indicating that the proproliferative influence of PHD2 does not involve alterations of its expression. Knockdown of PHD2 increased hypoxia-inducible factor (HIF)-1alpha expression, as expected, but we also found that HIF-1alpha knockdown abolished the inhibitory effect of PHD2 knockdown on PDGF-induced cyclin A expression. Therefore, we conclude that PHD2 promotes growth factor-induced responses of human VSMC, acting by HIF-1alpha-dependent mechanisms. Given the role of PHD2 as an oxygen sensor in mammalian cells, these results raise the possibility that PHD2 links VSMC proliferation to O(2) availability.
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PMID:Prolyl hydroxylase 2 deficiency limits proliferation of vascular smooth muscle cells by hypoxia-inducible factor-1{alpha}-dependent mechanisms. 1930 11