Connective tissue fibroblasts from highly regenerative mammals are refractory to ROS-induced cellular senescence.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31562333.
- Also identified by DOI 10.1038/s41467-019-12398-w and PMC identifier 6764955.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
A surveillance system in mammals constantly monitors cell activity to protect against aberrant proliferation in response to damage, injury and oncogenic stress. Here we isolate and culture connective tissue fibroblasts from highly regenerative mammals (Acomys and Oryctolagus) to determine how these cells interpret signals that normally induce cellular senescence in non-regenerating mammals (Mus and Rattus). While H<sub>2</sub>O<sub>2</sub> exposure substantially decreases cell proliferation and increases p53, p21, p16, and p19 in cells from mice and rats, cells from spiny mice and rabbits are highly resistant to H<sub>2</sub>O<sub>2</sub>. Quantifying oxygen consumption and mitochondrial stability, we demonstrate that increased intracellular H<sub>2</sub>O<sub>2</sub> is rapidly detoxified in regenerating species, but overwhelms antioxidant scavenging in cells from non-regenerative mammals. However, pretreatment with N-acetylcysteine (NAC) protects mouse and rat cells from ROS-induced cellular senescence. Collectively, our results show that intrinsic cellular differences in stress-sensing mechanisms partially explain interspecific variation in regenerative ability.
Medical subject headings
- Cellular Senescence
- Fibroblasts
- Reactive Oxygen Species
- Tumor Suppressor Proteins