ArticleProceedings of the National Academy of Sciences of the United States of America2002
Rapid activation of G2/M checkpoint after hypertonic stress in renal inner medullary epithelial (IME) cells is protective and requires p38 kinase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 80 citations in OpenAlex.
- Cells prioritize the regulation of cell mass density.Science advances · 2025Article
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- Osmotic Stress Interferes with DNA Damage Response and H2AX Phosphorylation in Human Keratinocytes.Cells · 2022Article
- Nuclear P38: Roles in Physiological and Pathological Processes and Regulation of Nuclear Translocation.International journal of molecular sciences · 2020Review
- p38 MAPK activity is associated with the histological degree of interstitial fibrosis in IgA nephropathy patients.PloS one · 2019Article
- Activating PAX gene family paralogs to complement PAX5 leukemia driver mutations.PLoS genetics · 2018Article
- Dynamic regulation of Cdr1 kinase localization and phosphorylation during osmotic stress.The Journal of biological chemistry · 2017Article
- Mapping out p38MAPK.American journal of reproductive immunology (New York, N.Y. : 1989) · 2017Review
- Global discovery of high-NaCl-induced changes of protein phosphorylation.American journal of physiology. Cell physiology · 2014Article
- The role of nitric oxide radicals in removal of hyper-radiosensitivity by priming irradiation.Journal of radiation research · 2013Article
- Hyperosmotic stress induces cell cycle arrest in retinal pigmented epithelial cells.Cell death & disease · 2013Article
- High NaCl- and urea-induced posttranslational modifications that increase glycerophosphocholine by inhibiting GDPD5 phosphodiesterase.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Cyclic compression-induced p38 activation and subsequent MMP13 expression requires Rho/ROCK activity in bovine cartilage explants.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2012Article
- Response to hyperosmotic stress.Genetics · 2012Review
- The p57 CDKi integrates stress signals into cell-cycle progression to promote cell survival upon stress.The EMBO journal · 2012Article
- DNA double-strand breaks induced by high NaCl occur predominantly in gene deserts.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- High NaCl-induced activation of CDK5 increases phosphorylation of the osmoprotective transcription factor TonEBP/OREBP at threonine 135, which contributes to its rapid nuclear localization.Molecular biology of the cell · 2011Article
- Downregulation of Gadd45beta expression by hepatitis C virus leads to defective cell cycle arrest.Cancer research · 2010Article
- Safeguarding entry into mitosis: the antephase checkpoint.Molecular and cellular biology · 2010Review
- Nuclear localization of p38 MAPK in response to DNA damage.International journal of biological sciences · 2009Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Cells in the kidney medulla are subject to variable and often extreme osmotic stress during concentration of the urine. Previous studies showed that renal inner medullary epithelial (IME) cells respond to hypertonicity by G(2) arrest. The purpose of the present study was to investigate the mechanisms involved in initiation and maintenance of G(2) arrest. Rapid initiation of G(2) arrest after UV radiation is mediated by p38 kinase. Here we find that p38 kinase is responsible for rapid initiation of the G(2) delay in IME cells after the hypertonic stress created by adding NaCl. High NaCl, but not high urea, rapidly initiates G(2) arrest. Inhibition of p38 kinase by SB202190 (10 microM) blocks the rapid initiation of this checkpoint both in an immortalized cell line (mIMCD3) and in second-passage IME cells from mouse renal inner medulla. p38 inhibition does not affect exit from G(2) arrest. The rapid initiation of G(2) arrest is followed by inhibition of cdc2 kinase, which is also prevented by SB202190. To assess the possible protective role of G(2) arrest, we measured DNA strand breaks as reflected by immunostaining against phospho-histone H2AX, which becomes phosphorylated on Ser-139 associated with DNA breaks. Abrogation of rapid G(2)/M checkpoint activation by SB202190 increases the histone H2AX phosphorylation in G(2)/M cells. We propose that the rapid initiation of G(2) delay by p38 kinase after hypertonicity protects the cells by decreasing the level of DNA breaks caused by aberrant mitosis entry.
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