It has been proposed that oxidative stress, elicited by high levels of reactive oxygen species, accelerates telomere shortening by erosion of telomeric DNA repeats. While most eukaryotes counteract telomere shortening by telomerase-driven addition of these repeats, telomeric loss in Drosophila is compensated by retrotransposition of the telomeric retroelements HeT-A, TART and TAHRE to chromosome ends. In this study we tested the effect of chronic exposure of flies to non-/sub-lethal doses of paraquat, which is a redox cycling compound widely used to induce oxidative stress in various experimental paradigms including telomere length analyses. Indeed, chronic paraquat exposure for five generations resulted in elevated transcriptional activity of both telomeric and non-telomeric transposable elements, and extended telomeric length in the tested fly lines. We propose that low oxidative stress leads to increased telomere length within Drosophila populations. For a mechanistic understanding of the observed phenomenon we discuss two scenarios: adaption, acting through a direct stimulation of telomere extension, or positive selection favoring individuals with longer telomeres within the population.
- MeSH
- Drosophila melanogaster účinky léků genetika MeSH
- genetická transkripce účinky léků MeSH
- homeostáza telomer účinky léků MeSH
- hormeze * MeSH
- paraquat farmakologie MeSH
- reaktivní formy kyslíku farmakologie MeSH
- retroelementy účinky léků MeSH
- telomery účinky léků fyziologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zkracování telomer účinky léků MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
KEY MESSAGE: Standard pathways involved in the regulation of telomere stability do not contribute to gradual telomere elongation observed in the course of A. thaliana calli propagation. Genetic and epigenetic changes accompanying the culturing of plant cells have frequently been reported. Here we aimed to characterize the telomere homeostasis during long term callus propagation. While in Arabidopsis thaliana calli gradual telomere elongation was observed, telomeres were stable in Nicotiana tabacum and N. sylvestris cultures. Telomere elongation during callus propagation is thus not a general feature of plant cells. The long telomere phenotype in Arabidopsis calli was correlated neither with changes in telomerase activity nor with activation of alternative mechanisms of telomere elongation. The dynamics of telomere length changes was maintained in mutant calli with loss of function of important epigenetic modifiers but compromised in the presence of epigenetically active drug zebularine. To examine whether the cell culture-induced disruption of telomere homeostasis is associated with the modulated structure of chromosome ends, epigenetic properties of telomere chromatin were analysed. Albeit distinct changes in epigenetic modifications of telomere histones were observed, these were broadly stochastic. Our results show that contrary to animal cells, the structure and function of plant telomeres is not determined significantly by the epigenetic character of telomere chromatin. Set of differentially transcribed genes was identified in calli, but considering the known telomere- or telomerase-related functions of respective proteins, none of these changes per se was apparently related to the elongated telomere phenotype. Based on our data, we propose that the disruption in telomere homeostasis in Arabidopsis calli arises from the interplay of multiple factors, as a part of reprogramming of plant cells to long-term culture conditions.
- MeSH
- Arabidopsis účinky léků genetika metabolismus MeSH
- chromatin genetika MeSH
- cytidin analogy a deriváty farmakologie MeSH
- druhová specificita MeSH
- ekotyp MeSH
- epigeneze genetická účinky léků MeSH
- histony metabolismus MeSH
- homeostáza telomer * účinky léků MeSH
- messenger RNA genetika metabolismus MeSH
- mutace genetika MeSH
- proteiny huseníčku metabolismus MeSH
- regenerace účinky léků MeSH
- rostlinné geny MeSH
- tabák genetika MeSH
- techniky tkáňových kultur * MeSH
- telomerasa metabolismus MeSH
- telomery metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- DMG-Gold,
- MeSH
- epigeneze genetická genetika účinky léků MeSH
- homeostáza telomer genetika účinky léků MeSH
- homeostáza fyziologie genetika MeSH
- hyperhomocysteinemie farmakoterapie genetika metabolismus MeSH
- lidé MeSH
- metylace DNA fyziologie genetika MeSH
- osteoporóza etiologie farmakoterapie metabolismus MeSH
- rostlinné extrakty terapeutické užití MeSH
- zkracování telomer genetika účinky léků MeSH
- Check Tag
- lidé MeSH
Telomeres consist of exanucleotide tandem repeats and proteins complexes at the end of chromosome ends. Telomeres shorten at each cell division, and as such telomere length is a marker of cellular age. Accelerated telomere shortening and cell senescence have been associated with a number of chronic medical conditions, including psychiatric disorders, where increased prevalence of age-related disorders and shorter telomere length have been reported. Shorter telomeres in psychiatric patients are thought to be the consequence of allostatic load, consisting in the overactivation of allostatic systems due to chronic exposure to severe medical conditions and failure to adapt to chronic stressful stimuli. Most of the studies on telomere length in psychiatry have focused on major depressive disorder, but recent findings have shown shorter leukocyte telomere length in bipolar disorder patients and suggested that lithium may counteract telomeres shortening. These findings provided new insights into the pathophysiology of bipolar disorder and the mechanism of action of lithium. In this review we will present findings from the literature on telomere length in bipolar disorder, with a specific focus on lithium. We will also discuss advances and limitations of published work as well as methodological issues and potential confounding factors that should be taken into account when designing research protocols to study telomere length.
- MeSH
- bipolární porucha krev diagnóza farmakoterapie MeSH
- homeostáza telomer účinky léků fyziologie MeSH
- lidé MeSH
- lithium farmakologie terapeutické užití MeSH
- telomery účinky léků fyziologie MeSH
- výsledek terapie MeSH
- zkracování telomer účinky léků fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
