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Senescence of Normal Human Fibroblasts Relates to the Expression of Ionotropic Glutamate Receptor GluR6/Grik2
Vikramjit K Zhawar1, Raj P Kandpal2, Raghbir S Athwal3
1Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA, U.S.A.
Background/Aim:
Glutamate receptor GRIK2, previously designated as GluR6, is best described in neuronal cells. However, its biological relevance in non-neuronal cells is not well understood. We have investigated the expression of this important protein in normal human fibroblasts as a function of cell proliferation.
Materials And Methods:
We introduced expression constructs of all five isoforms (A-E) of GRIK2 in normal human fibroblasts and investigated the cells for the presence and localization of GRIK2, as well as for cell proliferation and senescence over a period of 24 days.
Results:
The expression of GRIK2-A isoform led to immediate cessation of cell proliferation. However, the cell numbers increased by 1.5- to 9.0-fold in 24 days upon transfection with B, C, D and E isoforms, after which they entered a state of senescence. The decreased proliferation was reflected by incorporation of BrdU in only 2-8% of transfected cells even after culturing them for 16 days.
Conclusion:
Our results are indicative of an association between GRIK2 and aging of fibroblasts.
