Growth Factor Action and Intracellular pH Regulation in Fibroblasts. Evidence for a Major Role of the Na+/H+ Antiport
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Chinese hamster lung fibroblasts (CCl39) possess in their plasma membrane an amiloride-sensitive Na+/H+ antiport, activated by growth factors. Measurements of intracellular pH (pHi), using equilibrium distribution of benzoic acid, provide evidence for a major role of this antiport in 1) regulation of cytoplasmic pH, in response to an acute acid load or to varying external pH values, and 2) the increase in cytoplasmic pH (by 0.2-0.3 pH unit) upon addition of growth factors (alpha-thrombin and insulin) to G0/G1-arrested cells. Indeed, these two processes are Na+-dependent and amiloride-sensitive; furthermore, CCl39-derived mutant cells, lacking the Na+/H+ exchange activity, are greatly impaired in pHi regulation and present no cytoplasmic alkalinization upon growth factor addition. In wild type G0-arrested cells, the amplitude of the mitogen-induced alkalinization reflects directly the activity of the Na+/H+ antiport, and is tightly correlated with the magnitude of DNA synthesis stimulation. Therefore, we conclude that cytoplasmic pH, regulated by the Na+/H+ antiport, is of crucial importance in the mitogenic response.
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Cells are capable of buffering against extracellular reductions in pH to maintain alkaline pH of the cytoplasm.
“Cells are capable of buffering against extracellular reductions in pH to maintain alkaline pH of the cytoplasm (Johnson et al., 1976; L’allemain et al., 1984; Lindström and Sehlin, 1984; Pouyssegur et al., 1985; McBrian et al., 2013).”
From Toward Best Practices for Controlling Mammalian Cell Culture Environments (2022) · cites this paper as L’allemain et al., 1984
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References 26 · Cited by 350
- Authors
- L'Allemain, G., Paris, S., & Pouysségur, J.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- ORCID
- Pouysségur, J
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1984-05
- Volume
- 259
- Issue
- 9
- Pages
- 5809-5815
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1495429371
- Cited by
- 350
- References
- 26
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 3 · 2019: 3 · 2017: 3 · 2016: 4 · 2015: 2 · 2014: 1 · 2013: 5 · 2012: 3
- FWCI
- 17.75
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Keywords
- Na+/H+ antiport, intracellular pH regulation, fibroblasts, growth factor signaling, alpha-thrombin, insulin, mitogen response, DNA synthesis, amiloride sensitivity, cytoplasmic alkalinization, acid load, G0/G1 arrest, Chinese hamster lung fibroblasts
- MeSH terms
- Amiloride, Animals, Benzoates, Biological Transport, Carrier Proteins, Cell Cycle, Cell Line, Cell Membrane, Cricetulus, Fibroblasts, Growth Substances, Cricetinae, Hydrogen-Ion Concentration, Insulin, Intracellular Fluid, Kinetics, Lung, Mutation, Thrombin, Sodium-Hydrogen Exchangers, Benzoic Acid
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