Loading...
Please wait, while we are loading the content...
The NADPH oxidase Nox4 restricts the replicative lifespan of human endothelial cells
| Content Provider | Semantic Scholar |
|---|---|
| Author | Lener, Barbara Kozieł, Rafał Pircher, Haymo Huetter, Eveline Greussing, Ruth Herndler-Brandstetter, Dietmar Hermann, M. C. Unterluggauer, Hermann Jansen-Duerr, Pidder |
| Copyright Year | 2009 |
| Abstract | The free radical theory of aging proposes that ROS (reactive oxygen species) are major driving forces of aging, and are also critically involved in cellular senescence. Besides the mitochondrial respiratory chain, alternative sources of ROS have been described that might contribute to cellular senescence. Noxs (NADPH oxidases) are well-known sources of superoxide, which contribute to the antimicrobial capabilities of macrophages, a process involving the prototypical member of the family referred to as Nox2. However, in recent years non-phagocytic homologues of Nox2 have been identified that are involved in processes other than the host defence. Superoxide anions produced by these enzymes are believed to play a major role in signalling by MAPKs (mitogen-activated protein kinases) and stress-activated kinases, but could also contribute to cellular senescence, which is known to involve oxygen radicals. In HUVECs (human umbilical vein endothelial cells), Nox4 is predominantly expressed, but its role in replicative senescence of HUVECs remains to be elucidated. Using shRNA (small-hairpin RNA)-mediated knockdown of Nox4, implicating lentiviral vectors, we addressed the question of whether lifelong depletion of Nox4 in HUVECs would influence the senescent phenotype. We found a significant extension of the replicative lifespan of HUVECs upon knockdown of Nox4. Surprisingly, mean telomere length was significantly reduced in Nox4-depleted cells. Nox4 depletion had no discernable influence on the activity of MAPKs and stress-activated kinases, but reduced the degree of oxidative DNA damage. These results suggest that Nox4 activity increases oxidative damage in HUVECs, leading to loss of replicative potential, which is at least partly independent of telomere attrition. |
| Starting Page | 363 |
| Ending Page | 374 |
| Page Count | 12 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://ftp.ncbi.nlm.nih.gov/pub/pmc/34/f3/bj4230363.PMC2762686.pdf |
| PubMed reference number | 19681754v1 |
| Alternate Webpage(s) | https://doi.org/10.1042/BJ20090666 |
| DOI | 10.1042/bj20090666 |
| Journal | The Biochemical journal |
| Volume Number | 423 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Anions CYBB gene CYBB wt Allele Cell Aging DNA Damage Endothelial Cells Free Radicals Mitogen-Activated Protein Kinases Mitogens NADPH Dehydrogenase NADPH Oxidase NOX4 gene Reactive Oxygen Species Short Hairpin RNA Superoxides Tooth Attrition Umbilical vein Umbilicus (Anatomy) biological signaling telomere |
| Content Type | Text |
| Resource Type | Article |
