Functional role of GSK3β in p38MAPK mediated human amnion membrane senescence
| dc.creator | Lavu, Narmada | |
| dc.date.accessioned | 2021-09-01T15:12:09Z | |
| dc.date.available | 2021-09-01T15:12:09Z | |
| dc.date.created | 2019-08 | |
| dc.date.submitted | August 2019 | |
| dc.date.updated | 2021-09-01T15:12:10Z | |
| dc.description.abstract | Oxidative stress (OS) induced stress signaler p38 mitogen-activated protein kinase (p38MAPK) activation and fetal membrane senescence are associated with parturition. Our study determined changes in multipotent pro-cell cycle regulator glycogen synthase kinase (GSK) 3β and its regulation by p38MAPK in effecting senescence to further delineate the molecular mechanism involved in senescence. We report that OS resulted in phosphorylation of GSK3β (inactivation) and p38MAPK (activation) that was associated with cell cycle arrest and senescence in amnion cells. Inhibitors to GSK3β and p38MAPK verified their roles. GSK3β inactivation was associated with nuclear translocation of antioxidant nuclear factor erythroid 2–related factor 2 (Nrf2) and exosomal section of β-catenin. OS-induced P-p38MAPK activation is associated with functional down regulation of GSK3β and arrest of cell cycle progression and senescence of amnion cells. Lack of nuclear translocation of β-catenin and its excretion via exosomes further supports the postulation that GSK3β down regulation by p38MAPK may stop cell proliferation preceding cell senescence. A better understanding of molecular mechanisms of senescence will help develop therapeutic strategies to prevent preterm birth. | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.uri | https://hdl.handle.net/2152.3/11345 | |
| dc.subject | GSK3β | |
| dc.subject | p38MAPK | |
| dc.subject | fetal membranes | |
| dc.subject | senescence | |
| dc.subject | preterm labor | |
| dc.title | Functional role of GSK3β in p38MAPK mediated human amnion membrane senescence | |
| dc.type | Thesis | |
| dc.type.material | text | |
| thesis.degree.department | Cell Biology | |
| thesis.degree.grantor | The University of Texas Medical Branch at Galveston | |
| thesis.degree.level | Masters | |
| thesis.degree.name | Cell Biology (Masters) |