Dissertations and Theses
Date of Award
2018
Document Type
Thesis
Department
Biology
First Advisor
Karen Hubbard
Second Advisor
Mark Pezzano
Third Advisor
Tadmiri Venkatesh
Keywords
Aging, Fibroblast, hnRNP, A1, Premature, Senescence
Abstract
The role of heterogeneous nuclear ribonucleoproteins (hnRNP) in cellular senescence is yet to be defined. Cellular senescence is a terminal growth arrest in somatic cells. It is thought to be the consequence of telomeric shortening that acts as a DNA damage signal. Conversely, cells induced into premature senescence (SIPS) by oxidative stress, is independent of telomere attrition. Premature senescence has been proposed to be physiologically relevant as it can be induced by treatment with chemotherapeutic agents. In particular, we are studying the roles of hnRNP A1 and A2 in the maintenance of the senescence phenotype. hnRNPs are a family of RNA binding proteins that play key roles in various metabolic functions of the RNA such as splicing. hnRNP A1 in addition to its biochemical functions in RNA metabolism can bind to mRNAs for transport through the nuclear envelope. Our studies have shown that the protein level of hnRNP A1 is lower in senescent cells than in young cells. Thus, we have hypothesized that the altered expression of hnRNP A1 potentially modulates gene expression profiles and may maintain the senescent phenotype. We have observed that varying the levels of hnRNP A1 alters the expression levels of p21, p16 and ARF, all cell cycle regulators. To determine if this is the case during stress induced premature senescence (SIPS), IMR-90 fibroblast diploid normal lung cells were treated with a sub-lethal concentration of hydrogen peroxide that has been shown to induce premature senescence. To determine if hnRNPs may play a role in vivo, we measured their expression in rat hippocampal lysates isolated from rats treated with a combination of the chemotherapeutic drugs, doxorubicin and cyclophosphamide. We have shown here that stress induced premature senescence is not modulated in the same hnRNP dependent fashion as replicative senescence and possibly independent of p38MAPK.
Recommended Citation
Pechenyy, Yuriy, "The Effect of Stress Induced Premature Senescence on the Expression of Heterogeneous RibonucleoIeoprotein" (2018). CUNY Academic Works.
https://academicworks.cuny.edu/cc_etds_theses/722