Breast cancer drugs perturb fundamental vascular functions of endothelial cells by attenuating protein S-nitrosylation
| Autor: | Suvendu Giri, Yash T. Katakia, Palanivel Gajalakshmi, Suvro Chatterjee |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Endothelium Nitric Oxide Synthase Type III Physiology Down-Regulation Vasodilation Antineoplastic Agents Breast Neoplasms Pharmacology Nitric Oxide Nitric oxide Protein S 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Western blot Cell Movement Physiology (medical) medicine Animals Humans Cyclic guanosine monophosphate Cyclic GMP Nitrosoguanidines Tube formation medicine.diagnostic_test Endothelial Cells S-Nitrosylation 030104 developmental biology medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis Tamoxifen Citrate Female Endothelium Vascular |
| Zdroj: | Clinical and experimental pharmacologyphysiologyREFERENCES. 47(1) |
| ISSN: | 1440-1681 |
| Popis: | Cardiovascular side effects of broadly used chemotherapeutic drugs such as Tamoxifen citrate (TC), Capecitabine (CP) and Epirubicin (EP) among cancer survivors are well established. Nitric oxide (NO) is known to protect cardiovascular tissues under conditions of stress. NO can act through cyclic guanosine monophosphate (cGMP)-dependent and -independent pathways. Particularly, the S-nitrosylation of SH-groups in a protein by NO falls under cGMP-independent effects of NO. TC, CP, and EP are hypothesized as interfering with cellular protein S-nitrosylation, which, in turn, may lead to endothelial dysfunctions. The results show that all three drugs attenuate nitrosylated proteins in endothelial cells. A significant reduction in endogenous S-nitrosylated proteins was revealed by Saville-Griess assay, immunofluorescence and western blot. Incubation with the drugs causes a reduction in endothelial migration, vasodilation and tube formation, while the addition of S-nitrosoglutathione (GSNO) has a reversal of this effect. In conclusion, results indicate the possibility of decreased cellular nitrosothiols as being one of the reasons for endothelial dysfunctions under TC, CP and EP treatment. Identification of the down-regulated S-nitrosylated proteins so as to correlate their implications on fundamental vascular functions could be an interesting phenomenon. |
| Databáze: | OpenAIRE |
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