Effect of hypertension on lysosomal enzyme activities in aortic endothelial cells

Sasahara, Masakiyo; Hazama, Fumitada; Amano, Shigeru; Hayase, Yoneko; Yukioka, Naoya; Kawai, Jun; Kataoka, Hideo

doi:10.1016/0021-9150(88)90099-8

Cited by 12 publications

(3 citation statements)

References 24 publications

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“…It has been shown that the activity of cathepsin B, a protease participating in both intracellular proteolysis and extracellular matrix remodeling, correlates with aging and disease (Sloane, 1990;Sloane et al, 1990;Keppler et al, 2000), and that the activity of cathepsin B is up-regulated in atherosclerotic lesions in human and in aortic endothelial cells with aging in rat (Sasahara et al, 1988;Chen et al, 2002). Therefore, we regard the identification of cathepsin B identified as up-regulated in senescent HUVECs, as particularly important, because this result suggests that a proteomics-based approach using cultured HUVECs may prove to be a promising system to search for genes/ proteins involved not only in in vivo replicative senescence but also aging-related pathogenesis of endothelium such as arteriosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Searching for Genes Involved in Arteriosclerosis: Proteomic Analysis of Cultured Human Umbilical Vein Endothelial Cells Undergoing Replicative Senescence

Kamino

Hiratsuka

Toda

et al. 2003

Cell Struct. Funct.

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ABSTRACT. It is known that replicative senescence of endothelium in vivo contributes at least partially to agerelated vascular disorders such as arteriosclerosis. However, the genes involved in this process remain to be identified. In this study, we employed a proteomics-based approach to identify candidate genes using in vitro cultured human umbilical vein endothelial cells (HUVECs) as an experimental model for replicative senescence. By comparing protein spots from young and senescent HUVECs using two-dimensional electrophoresis, we identified three up-regulated proteins and five down-regulated proteins in senescent HUVECs as compared to young HUVECs, whose alteration was not observed during replicative senescence of primary human fibroblasts. Consistent results were obtained in Western blotting analysis using specific antibodies raised against some of these proteins, whereas there were no significant changes in the mRNA levels of these genes during senescence of HUVECs. Among them, cathepsin B, a protease participating in both intracellular proteolysis and extracellular matrix remodeling was observed to be dramatically up-regulated in senescent HUVECs and whose activity is known to be up-regulated in atherosclerotic lesions with senescence-associated phenotypes in vivo. Additional proteins, including cytoskeletal proteins and proteins involved in the processes of synthesis, turnover and modification of protein, were identified, whose function in endothelium was previously unsuspected. These proteins identified by a proteomics-based approach using cultured HUVECs may be involved not only in replicative senescence but also in functional alterations in vascular endothelial cells with senescence-associated phenotypes and may serve as molecular markers for these processes.

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Section: Discussionmentioning

confidence: 99%

Searching for Genes Involved in Arteriosclerosis: Proteomic Analysis of Cultured Human Umbilical Vein Endothelial Cells Undergoing Replicative Senescence

Kamino

Hiratsuka

Toda

et al. 2003

Cell Struct. Funct.

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“…30 Hence, it is possible that HPT7G acts as an aglycon with higher activity in the local vascular tissue, because b-glucuronidase activity is reported to be higher in SHRs than in normotensive WKYs. 33 In both cases, the position at which hesperetin is conjugated is very important for its biological activity because HPT3 0 G showed little biological activity. Further research is needed to reveal molecular actions of hesperetin glucuronides, considering their dynamics in local vascular tissue.…”

Section: Effects Of Hesperidin Glucuronide On H 2 O 2 -Induced Intrac...mentioning

confidence: 99%

Hesperidin metabolite hesperetin-7-O-glucuronide, but not hesperetin-3′-O-glucuronide, exerts hypotensive, vasodilatory, and anti-inflammatory activities

et al. 2013

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Orally ingested hesperidin (HES) is hydrolyzed into hesperetin in the gastrointestinal tract and conjugated during absorption. Hesperetin conjugates are the main circulating metabolites in human and rat plasma. We previously reported that glucosyl hesperidin (GHES), a water-soluble HES derivative, prevents hypertension via improvement of endothelial dysfunction in spontaneously hypertensive rats (SHRs). Although these hesperetin conjugates seem to be responsible for hypotensive and endothelium-dependent vasodilatory activities of dietary GHES, little is known about the mechanisms of action of these conjugated metabolites. Therefore, the aim of the present study was to investigate the effects of hesperetin-7-O-β-d-glucuronide (HPT7G) and hesperetin-3'-O-β-d-glucuronide (HPT3'G), which are the predominant HES metabolites in rat plasma, on blood pressure and endothelial function. Intravenous administration of HPT7G (5 mg kg(-1)) decreased blood pressure in anesthetized SHRs. HPT7G enhanced endothelium-dependent vasodilation in response to acetylcholine, but had no effect on endothelium-independent vasodilation in response to sodium nitroprusside (SNP) in aortas isolated from SHRs. HPT7G decreased hydrogen peroxide-induced intracellular adhesion molecule-1 and monocyte chemoattractant protein-1 mRNA expression in rat aortic endothelial cells. In contrast, HPT3'G had little effect on these parameters. In conclusion, HPT7G exerted hypotensive, vasodilatory and anti-inflammatory activities, similar to hesperetin and these effects are associated, in part, with the activity of GHES and HES to improve hypertension and endothelial dysfunction.

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“…In our previous study, an age-related marked increase of lysosomal activity was shown in the aortic endothelial cells in hypertensive animals Yamada et al 1983;Sasahara et al 1988). These augmente lysosomal enzymes were distributed in relation to the endothelial degeneration by electron microscopic histochemical study (Yamada et al 1980).…”

Section: Discussionmentioning

confidence: 85%

Analysis of Secretion and Expression of Platelet‐derived Growth Factor in Cultured Endothelial Cells From Stroke‐prone Spontaneously Hypertensive Rat

Iihara

Sasahara

Saeki

et al. 1993

Clin Exp Pharma Physio

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1. We characterized the endothelial cell-derived growth factors of SHRSP and Wistar Kyoto rats (WKY), respectively and found that platelet-derived growth factor (PDGF)-B chain related growth factor constituted a major portion of the mitogenic activity of the conditioned media of endothelial cells from both animals. There were no remarkable qualitative differences between the endothelial cell-derived growth factors of SHRSP and WKY. 2. Northern analysis revealed that the expression of PDGF-B chain was 2-4-fold enhanced in cultured aortic endothelial cells of SHRSP. This enhanced expression of PDGF-B chain, which may be induced under chronic hypertensive conditions, is suggested to contribute to the increase in endothelial cell-derived growth factors reported in this animal.

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Effect of hypertension on lysosomal enzyme activities in aortic endothelial cells

Cited by 12 publications

References 24 publications

Searching for Genes Involved in Arteriosclerosis: Proteomic Analysis of Cultured Human Umbilical Vein Endothelial Cells Undergoing Replicative Senescence

Searching for Genes Involved in Arteriosclerosis: Proteomic Analysis of Cultured Human Umbilical Vein Endothelial Cells Undergoing Replicative Senescence

Hesperidin metabolite hesperetin-7-O-glucuronide, but not hesperetin-3′-O-glucuronide, exerts hypotensive, vasodilatory, and anti-inflammatory activities

Analysis of Secretion and Expression of Platelet‐derived Growth Factor in Cultured Endothelial Cells From Stroke‐prone Spontaneously Hypertensive Rat

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