The Functional Significance of the Rho/Rho-Kinase Pathway in Human Erythrocytes
OBJECTIVE: Erythrocyte deformability, which can be influenced by various intracellular signaling mechanisms, such as nitric oxide, cAMP, cGMP, and protein kinases, is the most important physiological factor providing the blood flow in microcirculation. However, the functional significance of the Rho...
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| Format: | Article |
| Language: | English |
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Galenos Publishing House
2014-05-01
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| Series: | Turkish Journal of Hematology |
| Subjects: | |
| Online Access: | https://jag.journalagent.com/z4/download_fulltext.asp?pdir=tjh&un=TJH-46320 |
| _version_ | 1797921025931870208 |
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| author | R. Nalan Tiftik Oğuz K. Başkurt Seval Kul Kansu Büyükafşar |
| author_facet | R. Nalan Tiftik Oğuz K. Başkurt Seval Kul Kansu Büyükafşar |
| author_sort | R. Nalan Tiftik |
| collection | DOAJ |
| description | OBJECTIVE: Erythrocyte deformability, which can be influenced by various intracellular signaling mechanisms, such as nitric oxide, cAMP, cGMP, and protein kinases, is the most important physiological factor providing the blood flow in microcirculation. However, the functional significance of the Rho/Rho-kinase pathway, which contributes cell shape changes and the reorganization of the actin cytoskeleton, has yet to be explored in erythrocytes. Therefore, we examined the influence of several activators and inhibitors of Rho/Rho-kinase signaling on human erythrocyte deformability. METHODS: RhoA and ROCK-2 proteins were studied by western blotting. Influences of 2 Rho-kinase inhibitors, fasudil and Y-27632 (both 10-7 to 10-4 M), on erythrocyte deformability was determined by ektacytometer at various shear stresses (0-30 Pa) in the presence or absence of a known Rho activator, lysophosphatidic acid (LPA, 10-5 to 5x10-5 M, 1-15 min). RESULTS: LPA incubation reduced deformability with concomitant RhoA-GTP inhibition. Y-27632 and fasudil also decreased deformability, but had no effect on LPA-induced reduction of deformability. Rho inhibitor C3 had no effect on RhoA activation. Reduction in RhoA activation was induced by sub-hemolytic mechanical stress. CONCLUSION: Our findings may indicate that the Rho/Rho-kinase pathway could contribute to the regulation of deformability of human erythrocytes. |
| first_indexed | 2024-04-10T14:10:08Z |
| format | Article |
| id | doaj.art-9deee50aed7e452580cc9e245cc23f89 |
| institution | Directory Open Access Journal |
| issn | 1308-5263 |
| language | English |
| last_indexed | 2024-04-10T14:10:08Z |
| publishDate | 2014-05-01 |
| publisher | Galenos Publishing House |
| record_format | Article |
| series | Turkish Journal of Hematology |
| spelling | doaj.art-9deee50aed7e452580cc9e245cc23f892023-02-15T16:09:48ZengGalenos Publishing HouseTurkish Journal of Hematology1308-52632014-05-0131216817410.4274/tjh.2013.0115TJH-46320The Functional Significance of the Rho/Rho-Kinase Pathway in Human ErythrocytesR. Nalan Tiftik0Oğuz K. Başkurt1Seval Kul2Kansu Büyükafşar3Mersin University Faculty Of Medicine, Department Of Pharmacology, Mersin, TurkeyKoç University Faculty Of Medicine, İstanbul, TurkeyGaziantep University Faculty Of Medicine, Department Of Biostatistics, Gaziantep, TurkeyMersin University Faculty Of Medicine, Department Of Pharmacology, Mersin, TurkeyOBJECTIVE: Erythrocyte deformability, which can be influenced by various intracellular signaling mechanisms, such as nitric oxide, cAMP, cGMP, and protein kinases, is the most important physiological factor providing the blood flow in microcirculation. However, the functional significance of the Rho/Rho-kinase pathway, which contributes cell shape changes and the reorganization of the actin cytoskeleton, has yet to be explored in erythrocytes. Therefore, we examined the influence of several activators and inhibitors of Rho/Rho-kinase signaling on human erythrocyte deformability. METHODS: RhoA and ROCK-2 proteins were studied by western blotting. Influences of 2 Rho-kinase inhibitors, fasudil and Y-27632 (both 10-7 to 10-4 M), on erythrocyte deformability was determined by ektacytometer at various shear stresses (0-30 Pa) in the presence or absence of a known Rho activator, lysophosphatidic acid (LPA, 10-5 to 5x10-5 M, 1-15 min). RESULTS: LPA incubation reduced deformability with concomitant RhoA-GTP inhibition. Y-27632 and fasudil also decreased deformability, but had no effect on LPA-induced reduction of deformability. Rho inhibitor C3 had no effect on RhoA activation. Reduction in RhoA activation was induced by sub-hemolytic mechanical stress. CONCLUSION: Our findings may indicate that the Rho/Rho-kinase pathway could contribute to the regulation of deformability of human erythrocytes.https://jag.journalagent.com/z4/download_fulltext.asp?pdir=tjh&un=TJH-46320erythrocyte deformabilityrhoarho-kinasey-27632fasudillysophosphatidic acidc3 |
| spellingShingle | R. Nalan Tiftik Oğuz K. Başkurt Seval Kul Kansu Büyükafşar The Functional Significance of the Rho/Rho-Kinase Pathway in Human Erythrocytes Turkish Journal of Hematology erythrocyte deformability rhoa rho-kinase y-27632 fasudil lysophosphatidic acid c3 |
| title | The Functional Significance of the Rho/Rho-Kinase Pathway in Human Erythrocytes |
| title_full | The Functional Significance of the Rho/Rho-Kinase Pathway in Human Erythrocytes |
| title_fullStr | The Functional Significance of the Rho/Rho-Kinase Pathway in Human Erythrocytes |
| title_full_unstemmed | The Functional Significance of the Rho/Rho-Kinase Pathway in Human Erythrocytes |
| title_short | The Functional Significance of the Rho/Rho-Kinase Pathway in Human Erythrocytes |
| title_sort | functional significance of the rho rho kinase pathway in human erythrocytes |
| topic | erythrocyte deformability rhoa rho-kinase y-27632 fasudil lysophosphatidic acid c3 |
| url | https://jag.journalagent.com/z4/download_fulltext.asp?pdir=tjh&un=TJH-46320 |
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