Objective:To study the effects of angiotensin 1-7 (Ang1-7) on endothelial cell injury caused by oxidative stress.Methods: Human umbilical vein endothelial cells (HUVECs) were cultured and divided into blank control gr...Objective:To study the effects of angiotensin 1-7 (Ang1-7) on endothelial cell injury caused by oxidative stress.Methods: Human umbilical vein endothelial cells (HUVECs) were cultured and divided into blank control group, hydrogen peroxide and different Ang1-7 dose groups (1, 2 and 4 μmol/L Ang1-7 groups). The cell proliferation activity, the contents of antioxidant enzymes in cell culture medium, and the contents of endoplasmic reticulum stress molecules in cells were determined.Results: After 6, 12, 18 and 24 h of treatment, CCK-8 proliferation activity values of hydrogen peroxide group were significantly lower than those of blank control group, CCK-8 proliferation activity values of 1, 2 and 4 μmol/L Ang1-7 groups were significantly higher than those of hydrogen peroxide group, and the larger the Ang1-7 dose, the higher the CCK-8 proliferation activity values;after 24 h of treatment, SOD, GSH-Px, HO-1 and CAT contents in cell culture medium of hydrogen peroxide group were significantly lower than those of control group, and GRP78, XBP1 and CHOP contents in cells were significantly higher than those of control group;SOD, GSH-Px, HO-1 and CAT contents in cell culture medium of 1, 2 and 4 μmol/L Ang1-7 groups were significantly higher than those of hydrogen peroxide group, GRP78, XBP1 and CHOP contents in cells were significantly lower than those of hydrogen peroxide group, and the larger the Ang1-7 dose, the more significant the changes of above molecules in cell culture medium and cells.Conclusion: Angiotensin 1-7 has protective effect on the endothelial cell injury caused by oxidative stress.展开更多
Angiotensin-(1 - 7) [Ang-(1 - 7)] is an endogenous heptapeptide hormone of the renin-angiotensin system that has antiproliferative properties. The aim of this work was to evaluate the anti-proliferative and pro-apopto...Angiotensin-(1 - 7) [Ang-(1 - 7)] is an endogenous heptapeptide hormone of the renin-angiotensin system that has antiproliferative properties. The aim of this work was to evaluate the anti-proliferative and pro-apoptotic properties of Ang-(1 - 7) and of Ang-(1 - 7)-substituents 9-fluorenylmethyloxycarbonyl (Fmoc) e Ang II-derivatives containing the TOAC (2,2,6,6-tetramethylpiperidine-N-oxyl-4-amino-4-carboxylic acid) in normal (MCF10A) and in tumoral (MCF7) epithelial mammary cell lines. Both cell lines received an hCG and angiotensin peptides 24-hour treatment, in combination or alone followed by cell viability, apoptosis and cell cycle assays performed by flow cytometer (GUAVA). After hCG, Ang-(1 - 7), hCG + Ang-(1 - 7) and hCG + Ang-(1 - 7)-Fmoc treatments, MCF7 displayed cell viability decrease and mid-apoptosis increase. We also observed cell viability decrease in MCF10A after Ang-(1 - 7), Ang-(1 - 7) Fmoc and hCG + AngII Toac treatments. These cells had an increase in late apoptosis and necrosis after AngII Toac, hCG + Ang-(1 - 7) and hCG + Ang-(1 - 7)-Fmoc treatments. Regarding the cell cycle analysis, we did not observed any changes in cell cycle phases. In summary, cell viability was decreased and apoptosis (initial, mid and late) was increased after hCG and/or Ang-(1 - 7) peptides treatments. These results point out hCG and Ang-(1 - 7) as effective compounds to inhibit cell proliferation, since they decrease cell viability and increase apoptosis in both normal and in tumoral breast cells, being the effect more pronounced in the tumoral cell line. Our results support the idea of investigating more closely the putative use of these compounds as novel therapeutic agents for breast cancer.展开更多
文摘Objective:To study the effects of angiotensin 1-7 (Ang1-7) on endothelial cell injury caused by oxidative stress.Methods: Human umbilical vein endothelial cells (HUVECs) were cultured and divided into blank control group, hydrogen peroxide and different Ang1-7 dose groups (1, 2 and 4 μmol/L Ang1-7 groups). The cell proliferation activity, the contents of antioxidant enzymes in cell culture medium, and the contents of endoplasmic reticulum stress molecules in cells were determined.Results: After 6, 12, 18 and 24 h of treatment, CCK-8 proliferation activity values of hydrogen peroxide group were significantly lower than those of blank control group, CCK-8 proliferation activity values of 1, 2 and 4 μmol/L Ang1-7 groups were significantly higher than those of hydrogen peroxide group, and the larger the Ang1-7 dose, the higher the CCK-8 proliferation activity values;after 24 h of treatment, SOD, GSH-Px, HO-1 and CAT contents in cell culture medium of hydrogen peroxide group were significantly lower than those of control group, and GRP78, XBP1 and CHOP contents in cells were significantly higher than those of control group;SOD, GSH-Px, HO-1 and CAT contents in cell culture medium of 1, 2 and 4 μmol/L Ang1-7 groups were significantly higher than those of hydrogen peroxide group, GRP78, XBP1 and CHOP contents in cells were significantly lower than those of hydrogen peroxide group, and the larger the Ang1-7 dose, the more significant the changes of above molecules in cell culture medium and cells.Conclusion: Angiotensin 1-7 has protective effect on the endothelial cell injury caused by oxidative stress.
基金supported by Grants number 2007/56480-0,2008/54383-0 and 2011/10516-0 from the Sao Paulo Research Foundation(FAPESP)-Brazil.
文摘Angiotensin-(1 - 7) [Ang-(1 - 7)] is an endogenous heptapeptide hormone of the renin-angiotensin system that has antiproliferative properties. The aim of this work was to evaluate the anti-proliferative and pro-apoptotic properties of Ang-(1 - 7) and of Ang-(1 - 7)-substituents 9-fluorenylmethyloxycarbonyl (Fmoc) e Ang II-derivatives containing the TOAC (2,2,6,6-tetramethylpiperidine-N-oxyl-4-amino-4-carboxylic acid) in normal (MCF10A) and in tumoral (MCF7) epithelial mammary cell lines. Both cell lines received an hCG and angiotensin peptides 24-hour treatment, in combination or alone followed by cell viability, apoptosis and cell cycle assays performed by flow cytometer (GUAVA). After hCG, Ang-(1 - 7), hCG + Ang-(1 - 7) and hCG + Ang-(1 - 7)-Fmoc treatments, MCF7 displayed cell viability decrease and mid-apoptosis increase. We also observed cell viability decrease in MCF10A after Ang-(1 - 7), Ang-(1 - 7) Fmoc and hCG + AngII Toac treatments. These cells had an increase in late apoptosis and necrosis after AngII Toac, hCG + Ang-(1 - 7) and hCG + Ang-(1 - 7)-Fmoc treatments. Regarding the cell cycle analysis, we did not observed any changes in cell cycle phases. In summary, cell viability was decreased and apoptosis (initial, mid and late) was increased after hCG and/or Ang-(1 - 7) peptides treatments. These results point out hCG and Ang-(1 - 7) as effective compounds to inhibit cell proliferation, since they decrease cell viability and increase apoptosis in both normal and in tumoral breast cells, being the effect more pronounced in the tumoral cell line. Our results support the idea of investigating more closely the putative use of these compounds as novel therapeutic agents for breast cancer.
