Dihydrotestosterone protects human vascular endothelial cells from H2O2-induced apoptosis through inhibition of caspase-3, caspase-9 and p38 MAPK

The study was aimed at investigating the effects of L-cystathionine on vascular endothelial cell apoptosis and its mechanisms. Cultured human umbilical vein endothelial cells (HUVECs) were used in the study. Apoptosis of vascular endothelial cells was induced by homocysteine. Apoptosis, mitochondrial superoxide anion, mitochondrial membrane potential, mitochondrial permeability transition pore (MPTP) opening, and caspase-9 and caspase-3 activities were examined. Expression of Bax, Bcl-2, and cleaved caspase-3 was tested and BTSA1, a Bax agonist, and HUVEC Bax overexpression was used in the study. Results showed that homocysteine obviously induced the apoptosis of HUVECs, and this effect was significantly attenuated by the pretreatment with L-cystathionine. Furthermore, L-cystathionine decreased the production of mitochondrial superoxide anion and the expression of Bax and restrained its translocation to mitochondria, increased mitochondrial membrane potential, inhibited mitochondrial permeability transition pore (MPTP) opening, suppressed the leakage of cytochrome c from mitochondria into the cytoplasm, and downregulated activities of caspase-9 and caspase-3. However, BTSA1, a Bax agonist, or Bax overexpression successfully abolished the inhibitory effect of L-cystathionine on Hcy-induced MPTP opening, caspase-9 and caspase-3 activation, and HUVEC apoptosis. Taken together, our results indicated that L-cystathionine could protect against homocysteine-induced mitochondria-dependent apoptosis of HUVECs.

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Cytosine Arabinoside Induces Programmed Endothelial Cell Death Through the Caspase-3 Pathway

Biological Research For Nursing ◽

10.1177/1099800405286138 ◽

2006 ◽

Vol 7 (4) ◽

pp. 289-296 ◽

Cited By ~ 3

Author(s):

Ida M. (Ki) Moore ◽

Carrie J. Merkle ◽

Petra Miketova ◽

Renee K. Salyer ◽

Bonny J. Torres ◽

...

Keyword(s):

Endothelial Cells ◽

Dna Fragmentation ◽

Cytosine Arabinoside ◽

Caspase 3 ◽

Vascular Endothelial Cells ◽

Statistical Significance ◽

Annexin V ◽

Nonparametric Test ◽

Vascular Endothelial ◽

Induced Apoptosis

The anti-cancer effects of cytosine arabinoside (ARA-C) are well known. However, effects on nonmalignant cells have not been elucidated and may be important to understanding treatment-related toxicity. The purpose of this study was to examine the effect of ARA-C on nondividing vascular endothelial cells. The objectives were to determine the effects of ARA-C on cell viability and to ascertain whether ARA-C caused apoptosis in cultured vascular endothelial cells and hydrocortisone blunted caspase-3-induced apoptosis. Endothelial cells were cultured until confluent and mitotically quiescent then exposed to ARA-C (10-7 to 10-3 M) for 1 to 4 days. Some experiments involved cotreatment with hydrocortisone (10-11 ,10-10 ,10-4 , and 10-3 M). Light microscopy and the colorimetric MTS assay were used to measure viability. Fluorescent annexin-V and DNA fragmentation assays were used to measure apoptosis, and a fluorescence-based enzymatic assay was used to measure caspase-3 activity, which is one pathway involved in the apoptosis cascade. Two-way ANOVA or the appropriate nonparametric test was used to determine statistical significance in studies of viability and apoptosis. Oneway ANOVA was used to determine statistical significance for caspase-3 activity. Viability was decreased with higher concentrations of ARA-C and increased days of treatment. The percentage of apoptotic cells increased with higher concentrations of ARA-C and increased days of treatment. ARA-C-treated samples showed DNA fragmentation, indicative of apoptosis. Caspase-3 activity increased after ARA-C addition; hydrocortisone blunted this increase. ARA-C caused apoptosis in nondividing endothelial cells in culture. Hydrocortisone may protect against ARA-C-induced apoptosis by reducing caspase-3 activity.

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miR-181c-5p mediates apoptosis of vascular endothelial cells induced by hyperoxemia via ceRNA crosstalk

Scientific Reports ◽

10.1038/s41598-021-95712-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jizhi Wu ◽

Guangqi Zhang ◽

Hui Xiong ◽

Yuguang Zhang ◽

Gang Ding ◽

...

Keyword(s):

Endothelial Cells ◽

Oxygen Therapy ◽

Vascular Endothelial Cells ◽

Inhibitory Effect ◽

Vascular Endothelial ◽

Pulmonary Capillaries ◽

Pulmonary Capillary ◽

Capillary Endothelial Cells ◽

Nasal Inhalation ◽

Induced Apoptosis

AbstractOxygen therapy has been widely used in clinical practice, especially in anesthesia and emergency medicine. However, the risks of hyperoxemia caused by excessive O2 supply have not been sufficiently appreciated. Because nasal inhalation is mostly used for oxygen therapy, the pulmonary capillaries are often the first to be damaged by hyperoxia, causing many serious consequences. Nevertheless, the molecular mechanism by which hyperoxia injures pulmonary capillary endothelial cells (LMECs) has not been fully elucidated. Therefore, we systematically investigated these issues using next-generation sequencing and functional research techniques by focusing on non-coding RNAs. Our results showed that hyperoxia significantly induced apoptosis and profoundly affected the transcriptome profiles of LMECs. Hyperoxia significantly up-regulated miR-181c-5p expression, while down-regulated the expressions of NCAPG and lncRNA-DLEU2 in LMECs. Moreover, LncRNA-DLEU2 could bind complementarily to miR-181c-5p and acted as a miRNA sponge to block the inhibitory effect of miR-181c-5p on its target gene NCAPG. The down-regulation of lncRNA-DLEU2 induced by hyperoxia abrogated its inhibition of miR-181c-5p function, which together with the hyperoxia-induced upregulation of miR-181c-5p, all these significantly decreased the expression of NCAPG, resulting in apoptosis of LMECs. Our results demonstrated a ceRNA network consisting of lncRNA-DLEU2, miR-181c-5p and NCAPG, which played an important role in hyperoxia-induced apoptosis of vascular endothelial injury. Our findings will contribute to the full understanding of the harmful effects of hyperoxia and to find ways for effectively mitigating its deleterious effects.

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Salmonella Typhimurium L Forms Induce Vascular Endothelial Cell Apoptosis via Mitochondrial-dependent Pathway

10.21203/rs.3.rs-109267/v2 ◽

2021 ◽

Author(s):

Jinhai Zhai ◽

Cuiping Yang ◽

Tao Zhang ◽

Dengyu Chen

Keyword(s):

Endothelial Cells ◽

Salmonella Typhimurium ◽

Cell Apoptosis ◽

Vascular Endothelial Cells ◽

Vascular Endothelial Cell ◽

Intestinal Lumen ◽

Vascular Endothelial ◽

Caspase 9 ◽

Apoptosis Pathway ◽

Significant Difference

Abstract BackgroundSalmonella typhimurium is a pathogenic gram-negative bacterium, which is found primarily in the intestinal lumen. It often causes diarrhea in infants and young children and leads to food poisoning, as well as septicemia and septic shock. In this study, we investigated the phenomenon and mechanism of vascular endothelial cells apoptosis induced by Salmonella typhimurium L forms, in order to recognize and control Salmonella typhimurium L-form infection.Methods The apoptosis of vascular endothelial cells at 8 hours after infection with Salmonella typhimurium L forms was determined by flow cytometric assay and fluoroscopy of Annexin V-FITC/PI staining. Caspase-9 was detected by spectrophotometer. Results Salmonella typhimurium L forms can induce apoptosis of vascular endothelial cells, with significant difference in the apoptosis rate compared with the control. Caspase-9 expression is higher than that of the control. Conclusion The ability to induce cell apoptosis of vascular endothelial cells by Salmonella typhimurium L forms may be related to mitochondria apoptosis pathway depending on Caspase-9.

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