ABSTRACT
Objective: To detect the alterations of telomerase activity and the expression for oxidative stress responsive genes related with senescence during cellular replicative senescence and hydrogen peroxide-induced premature senescence in human embryonic lung fibroblasts (HELFs) in vitro. Methods: The HELFs were divided into young cells (22 population doubling levels, 22PDL) , mid-aged cells (35PDL) and replicative senes-cent cells (49PDL) and premature senescent cells induced by H(2)O(2)(premature senescence, PS). The telomerase activity was detected by ELISA assay during cellular replicative and premature senescence. The mRNA level of oxidative stress responsive genes related with senescence for Foxo1, Foxo3, Pdx1, apoA-I and MMP1 was per-formed by RT-Q-PCR separately. Results: The mRNA level for Foxo1, Foxo3, apoA-I and Pdx1 was decreased separately during cellular replicative senescence compared to that in the young-stage cells with statistical signifi-cance (P<0.05). The expression of MMP1 was up-regulated 5.1-fold obviously (P<0.05). In premature senes-cence, the mRNA level was only decreased for Foxo1, Foxo3 and apoA-I, but up-regulated 2.3-fold and 6.2-fold for Pdx1 and MMP1 respcetively vs 22PDL significantly (P<0.05). The telomerase activity in young cells was not detected, and it increased in mid-aged cells and replicative senescence stages during cellular replicative se-nescence as compared to 22PDL with statistical significance (P<0.05). The telomerase activity in premature se-nescence was highly active. Conclusion: The expression for genes related with senescence has differences be-tween replicative and premature senescence and hydrogen peroxide modifies their expression levels. The telomer-ase activity has been going up with increased PDLs.
Subject(s)
Aging/genetics , Cellular Senescence/drug effects , Fibroblasts/drug effects , Hydrogen Peroxide/pharmacology , Telomerase/genetics , Cell Proliferation/drug effects , Cells, Cultured , Cellular Senescence/genetics , DNA (Cytosine-5-)-Methyltransferases/metabolism , Embryo, Mammalian , Gene Expression/drug effects , HumansABSTRACT
Cell therapy is thought to have a central role in restorative therapy, which aims to restore the function of the damaged nervous system. Neural stem cells (NSCs) can differentiate into neurons, astrocytes and oligodendrocytes. The purpose of this study was to evaluate the therapeutic effects of transplanting NSCs into rats which have the animal model of Alzheimer's disease (AD). NSCs from the hippocampus and NSCs-derived glial cells labeled with 5'-Bromo-2'-deoxyuridine (BrdU) were transplanted into two groups of transected rat basal forebrain. Nestin staining, glial fibrillary acidic protein (GFAP) staining and double-labeling immunofluorescence were used to detect the engrafted cells in the basal forebrain. Immunohistochemical detection of p75(NGFR) showed that the number of cholinergic neurons of the NSCs-transplanted group was significant higher than that of the glia-transplanted group in medial septum (MS) and vertical diagonal branch (VDB) (P<0.05). Learning and memory abilities were also measured by Y-maze test. The results indicate that transplanted NSCs can differentiate into cholinergic neurons, which may play an important role in the therapeutic effects of transplanted NSCs.