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Intracellular reactive oxygen species mediate the linkage of Na+/K+-ATPase to hypertrophy and its marker genes in cardiac myocytes.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Xie, Zhongjian Kometiani, Peter Liu, Jianwei Li, Jiliang Shapiro, Joseph Isaac Askari, Amir |
| Copyright Year | 1999 |
| Abstract | We showed before that in cardiac myocytes partial inhibition of Na+/K+-ATPase by nontoxic concentrations of ouabain causes hypertrophy and transcriptional regulations of growth-related marker genes through multiple Ca2+-dependent signal pathways many of which involve Ras and p42/44 mitogen-activated protein kinases. The aim of this work was to explore the roles of intracellular reactive oxygen species (ROS) in these ouabain-initiated pathways. Ouabain caused a rapid generation of ROS within the myocytes that was prevented by preexposure of cells to N-acetylcysteine (NAC) or vitamin E. These antioxidants also blocked or attenuated the following actions of ouabain: inductions of the genes of skeletal alpha-actin and atrial natriuretic factor, repression of the gene of the alpha3-subunit of Na+/K+-ATPase, activation of mitogen-activated protein kinases, activation of Ras-dependent protein synthesis, and activation of transcription factor NF-kappaB. Induction of c-fos and activation of AP-1 by ouabain were not sensitive to NAC. Ouabain-induced inhibition of active Rb+ uptake through Na+/K+-ATPase and the resulting rise in intracellular Ca2+ were also not prevented by NAC. A phorbol ester that also causes myocyte hypertrophy did not increase ROS generation, and its effects on marker genes and protein synthesis were not affected by NAC. We conclude the following: (a) ROS are essential second messengers within some but not all signal pathways that are activated by the effect of ouabain on Na+/K+-ATPase; (b) the ROS-dependent pathways are involved in ouabain-induced hypertrophy; (c) increased ROS generation is not a common response of the myocyte to all hypertrophic stimuli; and (d) it may be possible to dissociate the positive inotropic effect of ouabain from its growth-related effects by alteration of the redox state of the cardiac myocyte. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.jbc.org/content/274/27/19323.full.pdf |
| Alternate Webpage(s) | http://www.utoledo.edu/med/depts/physpharm/pdfs/faculty/askari/19323.pdf |
| Alternate Webpage(s) | https://mds.marshall.edu/cgi/viewcontent.cgi?article=1030&context=sp_psr |
| PubMed reference number | 10383443v1 |
| Volume Number | 274 |
| Issue Number | 27 |
| Journal | The Journal of biological chemistry |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Acetylcysteine Antioxidants Atrial Natriuretic Factor Calcium ion FOS gene Heart Atrium Hypertrophy Mitogen-Activated Protein Kinases Mitogens Muscle Cells Myocytes, Cardiac Natriuretic Hormones Ouabain Oxidation-Reduction Phorbol Esters Phorbols Protein Biosynthesis Rubidium TRANSCRIPTION FACTOR Transcription, Genetic genetic linkage negative regulation of reactive oxygen species biosynthetic process second messenger |
| Content Type | Text |
| Resource Type | Article |
