Massive telomere loss and telomerase RNA expression in dexamethasone-induced apoptosis in mouse thymocytes.
Apoptosis is a well-recognized process of cell death occurring under several physiological and pathological conditions and represents the principal mechanism involved in cell selection in the thymus. Glucocorticoids are well known to stimulate apoptosis in rat thymocytes. However, it is unclear whether the same changes occur after in vivo glucocorticoid treatment in mice. Chromosomal stability and cell viability require a proficient telomeric end-capping function. Cells with critical telomere shortening and telomerase dysfunction undergo increased apoptosis. In turn, the change in telomere function in cells undergoing apoptosis is not fully characterized. In order to investigate this, we studied the changes in thymocytes after dexamethasone administration in BALB/c mice. The loss of normal thymocytes coincided with the appearance of small dense cells with characteristic features of apoptosis including condensed chromatin, internucleosomal DNA cleavage, and a "hypodiploid" peak on flow cytometry, which suggested that dexamethasone-induced thymocyte apoptosis in BALB/c mice could be considered a well-defined experimental model for studying apoptotic processes. Dexamethasone-treated thymocytes exhibited rapid and dynamic loss of telomeric sequences and up-regulation of telomerase RNA as an early event in the apoptotic process. Telomerase activity was unchanged in this event. Thereafter, telomere gain associated with an increase in telomerase activity occurred in the regenerative process of the thymus. These results suggest a role of telomere loss and up-regulation of telomerase RNA as key apoptosis sensors.
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001835:Body Weight; D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects; D017931:DNA Primers / Q000737:chemistry; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012313:RNA / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics*; D016615:Telomere / Q000378:metabolism*; D013950:Thymus Gland / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
D017931:DNA Primers; D005938:Glucocorticoids; D012313:RNA; D003907:Dexamethasone; D004247:DNA; D019098:Telomerase