• 제목/요약/키워드: ANG-2

검색결과 4,981건 처리시간 0.031초

Expression and Purification of Recombinant Human Angiopoictin-2 and Its Analog in Chinese Hamster Ovary Cells

  • 황수정;김인준;고규영;이균민
    • 한국생물공학회:학술대회논문집
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    • 한국생물공학회 2001년도 추계학술발표대회
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    • pp.459-462
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    • 2001

  • Angiopoietin-2 (Ang2) is a naturally occurring antagonist for angiopoietin-l (Angl) and its Tie2 receptor during vasculogenesis, Although angiopoietins have been expressed in several mammalian cell lines, their expression levels are low. Recombinant Chinese hamster ovary (CHO) cell lines expressing a high level of human Ang2 or its analog, human $Ang2_{443}$, with an amino-terminal FLAG-tag were constructed by transfecting the expression vectors into dhfr-deficient CHO cells and subsequent gene amplification in medium containing stepwise increments in methotrexate level. Secreted Ang2 or human $Ang2_{443}$ were purified from the cultured medium using an anti-FLAG- agarose affinity chromatography, The purified Ang2 and $Ang2_{443}$ migrated on SOS-PAGE as a broad band, characteristic of glycosylated protein. Their biological activity in vitro was demonstrated in a serum deprivation-induced apoptosis assay. Ang2 at high concentration, like AngI, can be an apoptosis survival factor for endothelial cells through the activation of the Tie2 receptor.

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Downregulation of Angiotensin II-Induced 12-Lipoxygenase Expression and Cell Proliferation in Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rats by CCL5

  • Kim, Jung-Hae;Kim, Hee-Sun
    • The Korean Journal of Physiology and Pharmacology
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    • 제13권5호
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    • pp.385-392
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    • 2009

  • Angiotensin II (Ang II) plays an important role in vascular hypertension. The role of the chemokine CCL5 on Ang II-induced activities in vascular smooth muscle cells (VSMCs) has not been studied. In this study, we elucidated the effect of CCL5 on Ang II-induced 12-lipoxygenase (LO) expression and cell proliferation in spontaneously hypertensive rats (SHR) VSMCs. CCL5 decreased Ang II-induced 12-LO mRNA expression and protein production, and it increased Ang II type 2 ($AT_2$) receptor expression in SHR VSMCs. The inhibitory effect of CCL5 on Ang II-induced 12-LO mRNA expression was mediated through the $AT_2$ receptor. Although treatment of CCL5 alone induced SHR VSMCs proliferation, CCL5 inhibited Ang II-induced VSMCs proliferation and PD123,319, an $AT_2$ receptor antagonist, blocked the inhibitory effect of CCL5 on Ang II-induced VSMCs proliferation. Phosphorylation of p38 was detected in VSMCs treated with Ang II or CCL5 alone. But, decrease of p38 phosphorylation was detected in VSMCs treated with Ang II and CCL5 simultaneously (Ang II/CCL5) and PD123,319 increased p38 phosphorylation in VSMCs treated with Ang II/CCL5. Therefore, these results suggest that the inhibitory effect of CCL5 on Ang II-induced VSMCs proliferation is mediated by the $AT_2$ receptor via p38 inactivation, and CCL5 may play a beneficial role in Ang II-induced vascular hypertension.

  • https://doi.org/10.4196/kjpp.2009.13.5.385 인용 PDF KSCI

Angiotensin-(1-9) ameliorates pulmonary arterial hypertension via angiotensin type II receptor

  • Cha, Seung Ah;Park, Byung Mun;Kim, Suhn Hee
    • The Korean Journal of Physiology and Pharmacology
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    • 제22권4호
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    • pp.447-456
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    • 2018

  • Angiotensin-(1-9) [Ang-(1-9)], generated from Ang I by Ang II converting enzyme 2, has been reported to have protective effects on cardiac and vascular remodeling. However, there is no report about the effect of Ang-(1-9) on pulmonary hypertension. The aim of the present study is to investigate whether Ang-(1-9) improves pulmonary vascular remodeling in monocrotaline (MCT)-induced pulmonary hypertensive rats. Sprague-Dawley rats received Ang-(1-9) ($576{\mu}g/kg/day$) or saline via osmotic mini-pumps for 3 weeks. Three days after implantation of osmotic mini-pumps, 50 mg/kg MCT or vehicle were subcutaneously injected. MCT caused increases in right ventricular weight and systolic pressure, which were reduced by co-administration of Ang-(1-9). Ang-(1-9) also attenuated endothelial damage and medial hypertrophy of pulmonary arterioles as well as pulmonary fibrosis induced by MCT. The protective effects of Ang-(1-9) against pulmonary hypertension were inhibited by Ang type 2 receptor ($AT_2R$) blocker, but not by Mas receptor blocker. Additionally, the levels of LDH and inflammatory cytokines, such as $TNF-{\alpha}$, MCP-1, $IL-1{\beta}$, and IL-6, in plasma were lower in Ang-(1-9) co-treated MCT group than in vehicle-treated MCT group. Changes in expressions of apoptosis-related proteins such as Bax, Bcl2, Caspase-3 and -9 in the lung tissue of MCT rats were attenuated by the treatment with Ang-(1-9). These results indicate that Ang-(1-9) improves MCT-induced pulmonary hypertension by decreasing apoptosis and inflammatory reaction via $AT_2R$.

  • https://doi.org/10.4196/kjpp.2018.22.4.447 인용 PDF KSCI