Browsing by Subject "nuclear lamin"

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    Expression of Nuclear Lamin Proteins in Endothelial Cells is Sensitive to Cell Passage and Fluid Shear Stress
    (Springer, 2018-02) Jiang, Yizhi; Ji, Julie Y.; Engineering Technology, School of Engineering and Technology
    Introduction Vascular cells are regulated by continuous hemodynamic forces in vivo, and mechanical forces such as shear stress are proposed to involve in the progression of cardiovascular diseases such as atherosclerosis. Lamin A/C makes up the nuclear lamina, which structurally supports the nucleus while also functionally participates in chromatin organization and gene transcription. Diseases caused by lamin or other nuclear proteins are called laminopathies. One example, Hutchinson Gilford Progeria Syndrome (HGPS) where young patients show signs of accelerated aging, is caused by de novo mutations on the lamin A/C gene. Vasculature of HGPS patients shares many similarities with people of advanced age, suggesting a role for lamin in vascular aging. Methods In this study, we examined how arterial shear stress affects lamin A/C expression in bovine aortic endothelial cells at different population doubling levels (PDL). We also used fluorescence image analysis to examine nuclear shape changes with shear stress and PDL. Results Our results suggest that laminar shear stress downregulated lamin A/C expression in low PDL cells, but the effect was reversed in high PDL cells. Nuclear shape changes were more prominent after shear stress in low PDL cells. Moreover, lamin A/C accumulated more at the nuclear periphery after exposure to shear stress. Conclusions Overall, our results indicate that both shear stress and cell passage can have an impact on lamin expressions at transcriptional and translational levels, as we continue to understand the effect of shear stress on endothelial lamina as part of the vascular aging process.
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    Lamin A/C Regulates Endothelial Glucocorticoid Receptor Nuclear Translocation in Response to Cyclic Stretch
    (2016) Nayebosadri, Arman; Ji, Julie Y.; Biomedical Engineering, School of Engineering and Technology
    The glucocorticoid receptor (GR) has multiple phosphorylation sites that can be activated by MAPKs, which have been previously shown to be activated in response to cyclic stretch in endothelial cells. It is possible therefore that physiological and/or pathological degree of cyclic stretch may also initiate phosphorylation-induced changes in GR subcellular localization as we previously showed with shear stress. However, little is known about the effects of cyclic stretch on glucocorticoid receptor (GR) activity in endothelial cells. We used control and lamin shRNA BAECs and subjected them to ligand (dexamethasone) treatment, physiological stretch (10% at 1 Hz), or pathological stretch (20% at 1 Hz or 10% at 2 Hz), in order to evaluate GR nuclear translocation in endothelial cells with and without lamin A/C as well as potential upstream protein regulators of GR subcellular movement during cyclic stretch. Upon exposure to pathological degrees of stretching, control shRNA BAECs showed greater nuclear concentration of GR at each time point compared to when they were stretched at physiological parameters. The response of GR in lamin-deficient cells to cyclic stretching was relatively non-existent compared to that observed in control shRNA cells. Our results suggest that in cells with lamin A/C, cyclic stretch activates GR through the JNK pathway, and ERK has some inhibitory role on GR nuclear translocation. DUSP proteins become upregulated in response to stretch as a result of GR activation (DUSP1) or by stretch-induced MAPK signaling. In lamin-deficient cells, only the combination of cyclic stretch and p38 inhibition was able to induce marginal nuclear translocation. Increased MAPK phosphorylation due to lamin A/C absence could drive DUSP expression as a negative feedback mechanism. Upregulation of the cytoplasmic DUSP6 suggests a significant role of ERK in reducing GR sensitivity to mechanical strain.