Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P39060 (endostatin)
 2,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The anti-angiogenic agents angiostatin and endostatin have been shown to affect endothelial cell migration in a number of studies. We have examined the effect of these agents on intracellular signalling pathways known to regulate endothelial cell migration and proliferation/survival. Both agents inhibited fibroblast growth factor (FGF)-, and vascular endothelial growth factor (VEGF)-mediated migration of primary human microvascular endothelial cells and affected vascular formation in the embryoid body model. However, using phosphospecific antibodies we could not detect any effect of angiostatin or endostatin on phospholipase C-gamma (PLC-gamma), Akt/PKB, p44/42 mitogen-activated protein kinase (MAPK), p38 MAPK and p21-activated kinase (PAK) activity. Furthermore, using a glutathione S-transferase (GST)-PAK pull-down assay, we could not detect any effect on Rac activity. We conclude that angiostatin and endostatin inhibit chemotaxis, without affecting intracellular signalling pathways known to regulate endothelial migration and proliferation/survival.
 ...
PMID:Angiostatin and endostatin inhibit endothelial cell migration in response to FGF and VEGF without interfering with specific intracellular signal transduction pathways. 1258 31

Previously we demonstrated that domain 5 (D5) of high-molecular-weight kininogen (HK) inhibits neovascularization in the chicken chorioallantoic membrane (CAM) assay and further found that kallikrein cleaved HK (HKa) inhibited FGF2-and VEGF-induced neovascularization, and thus was antiangiogenic. In this study, we sought to demonstrate whether uncleaved HK stimulates neovascularization and thus is proangiogenic. The chick chorioallantoic membrane was used as an in ovo assay of angiogenesis. Low-molecular-weight kininogen stimulates angiogenesis, indicating that D5 is not involved. Bradykinin stimulates neovascularization equally to HK and LK and is likely to be responsible for the effect of HK. A murine monoclonal antibody to HK (C11C1) also recognizes a similar component in chicken plasma as detected by surface plasmon resonance. Angiogenesis induced by FGF2 and VEGF is inhibited by this monoclonal antibody and is a more potent inhibitor of neovascularization induced by VEGF than an integrin alphavbeta3 antibody (LM 609). Our postulate that C11C1 inhibits the stimulation of angiogenesis by HK was confirmed when either C11C1 or D5 completely inhibited angiogenesis in the CAM induced by HK. Growth of human fibrosarcoma (HT-1080) on the CAM was inhibited by GST-D5 and C11C1. These results indicate HK is proangiogenic probably by releasing bradykinin and that a monoclonal antibody directed to HK could serve as an antiangiogenic agent with a potential for inhibiting tumor angiogenesis and other angiogenesis-mediated disorders.
 ...
PMID:Inhibition of angiogenesis by antibody blocking the action of proangiogenic high-molecular-weight kininogen. 1287 54

The activities of antioxidant enzymes viz. glutathione reductase, GR; superoxide dismutase, SOD; peroxidase, POD; catalase, CAT and glutathione-S-transferase, GST and alkaloid accumulation were investigated in leaf pairs (apical, middle, basal) and in roots of Catharanthus roseus seedlings under the conditions of different nitrogen sources (20 mM KNO(3) and 2 mM NH(4)Cl) and salinity, in the absence (non-saline control) and in the presence of 100 mM NaCl in the nutrient solution. Salinity caused a reduction in plant biomass. The biomass production of ammonium-fed plants was lower than that of nitrate-fed plants. The antioxidant enzymes exhibited higher activity in saline-treated plants. Changes in antioxidant enzyme activity caused by different nitrogen sources differed in all leaf pairs, as well as in roots of C. roseus. Ammonium-fed plants showed higher CAT, GR and GST activity in leaf pairs as well as in roots, while POD and SOD activity were higher in nitrate-fed plants. Higher peroxidase activity concomitant with the increased accumulation of alkaloid was found in all leaf pairs, as well as in roots of C. roseus of NO(3)(-) fed plants as compared to NH(4)(+) fed plants.
 ...
PMID:Effect of salinity and different nitrogen sources on the activity of antioxidant enzymes and indole alkaloid content in Catharanthus roseus seedlings. 1636 Jul 99

Intracranial stenosis is a common etiology for ischemic stroke. Due to limitations of imaging studies, there are limited data on the prevalence of symptomatic and asymptomatic intracranial stenosis. Intracranial stenosis is more prevalent in Asian, Hispanic, and African-American populations. The reported proportion of patients with symptomatic intracranial stenosis among those hospitalized for ischemic cerebral events varies from 1% in non-Hispanic whites to as high as 50% in Asian populations. In population-based studies, the estimated prevalence of symptomatic intracranial disease varies from 1 in 100,000 for whites to 15 in 100,000 in African Americans. A Chinese population-based study reported intracranial stenosis in 7% of the population aged more than 40 years. Autopsy studies have noted intracranial atherosclerotic disease in about 23% of population in the 6th decade and 80% of population in the 9th decade of life. Angiotensin-converting enzyme polymorphisms, plasma endostatin/vascular endothelial growth factor ratio, glutathione S-transferase omega-1 gene polymorphism, and plasma homocysteine levels are non-modifiable risk factors noted to be associated with intracranial stenosis. Hypertension and serum lipid profile are major modifiable risk factors, whereas sickle cell disease is an uncommon risk factor that can be managed to reduce risk. Associations of intracranial atherosclerosis with diabetes mellitus, metabolic syndrome, Alzheimer's disease, aortic plaques, radiotherapy, and meningitis are less well documented.
 ...
PMID:Epidemiology of intracranial stenosis. 1980 51