A Potassium Ionophore (valinomycin) Inhibits Lymphocyte Proliferation by Its Effects on the Cell Membrane

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1976 Oct 1

PMID 1068473

Citations 13

Authors

R P Daniele

S K Holian

Affiliations

Soon will be listed here.

Abstract

Valinomycin is a depsipeptide antibiotic which selectively translocates potassium across biologic membranes. This potassium ionophore was observed to inhibit phytohemagglutinin-stimulated blastogenesis and proliferation in human lymphocytes. The effect was not due to toxicity to the cells, nor appeared to be due to the effects of valinomycin as an uncoupler of oxidative phosphorylation. Furthermore, the inhibitory effect on phytohemagglutinin stimulated lymphocytes was prevented by increasing the potassium concentration of the external media. These results suggest that the interaction of mitogens with specific receptors at the cell membrane may involve mechanisms affecting cation fluxes and membrane potential. These ionic events may play a role in the transduction of membrane signals for lymphocyte stimulation.

Citing Articles

Attenuated growth factor signaling during cell death initiation sensitizes membranes towards peroxidation.

Gollowitzer A, Pein H, Rao Z, Waltl L, Bereuter L, Loeser K Nat Commun. 2025; 16(1):1774.

PMID: 40000627 PMC: 11861335. DOI: 10.1038/s41467-025-56711-2.

PI(18:1/18:1) is a SCD1-derived lipokine that limits stress signaling.

Thurmer M, Gollowitzer A, Pein H, Neukirch K, Gelmez E, Waltl L Nat Commun. 2022; 13(1):2982.

PMID: 35624087 PMC: 9142606. DOI: 10.1038/s41467-022-30374-9.

Development of a neurotoxicity assay that is tuned to detect mitochondrial toxicants.

Delp J, Funke M, Rudolf F, Cediel A, Bennekou S, van der Stel W Arch Toxicol. 2019; 93(6):1585-1608.

PMID: 31190196 DOI: 10.1007/s00204-019-02473-y.

CesH Represses Cereulide Synthesis as an Alpha/Beta Fold Hydrolase in .

Tian S, Xiong H, Geng P, Yuan Z, Hu X Toxins (Basel). 2019; 11(4).

PMID: 31010094 PMC: 6521208. DOI: 10.3390/toxins11040231.

Structurally diverse natural products that cause potassium leakage trigger multicellularity in Bacillus subtilis.

Lopez D, Fischbach M, Chu F, Losick R, Kolter R Proc Natl Acad Sci U S A. 2008; 106(1):280-5.

PMID: 19114652 PMC: 2629187. DOI: 10.1073/pnas.0810940106.

References

Averdunk R, Lauf P . Effects of mitogens on sodium-potassium transport, 3H-ouabain binding, and adenosine triphosphatase activity in lymphocytes. Exp Cell Res. 1975; 93(2):331-42. DOI: 10.1016/0014-4827(75)90458-9. View

HODGKIN A, Katz B . The effect of sodium ions on the electrical activity of giant axon of the squid. J Physiol. 1949; 108(1):37-77. PMC: 1392331. DOI: 10.1113/jphysiol.1949.sp004310. View

Boyum A . Isolation and removal of lymphocytes from bone marrow of rats and guinea-pigs. Scand J Clin Lab Invest Suppl. 1968; 97:91-106. View

BLONDIN G . Isolation of a divalent cation ionophore from beef heart mitochondria. Biochem Biophys Res Commun. 1974; 56(1):97-105. DOI: 10.1016/s0006-291x(74)80320-7. View

Tosteson M, Lau F, Tosteson D . Incorporation of a functional membrane glycoprotein into lipid bilayer membranes. Nat New Biol. 1973; 243(125):112-4. View

COVINO B . Local anesthesia. 1. N Engl J Med. 1972; 286(18):975-83. DOI: 10.1056/NEJM197205042861805. View

PRESSMAN B . Properties of ionophores with broad range cation selectivity. Fed Proc. 1973; 32(6):1698-703. View

Hoffman J, LARIS P . Determination of membrane potentials in human and Amphiuma red blood cells by means of fluorescent probe. J Physiol. 1974; 239(3):519-52. PMC: 1330957. DOI: 10.1113/jphysiol.1974.sp010581. View

Schellekens P, EIJSVOOGEL V . Lymphocyte transformation in vitro. 3. Mechanism of stimulation in the mixed lymphocyte culture. Clin Exp Immunol. 1970; 7(2):229-39. PMC: 1712834. View

10.

QUASTEL M, Kaplan J . Early stimulation of potassium uptake in lymphocytes treated with PHA. Exp Cell Res. 1970; 63(1):230-3. DOI: 10.1016/0014-4827(70)90360-5. View

11.

QUASTEL M, Kaplan J . Inhibition by ouabain of human lymphocyte transformation induced by phytohaemagglutinin in vitro. Nature. 1968; 219(5150):198-200. DOI: 10.1038/219198a0. View

12.

PRESSMAN B . Ionophorous antibiotics as models for biological transport. Fed Proc. 1968; 27(6):1283-8. View

13.

Stewart C, Ingram M . A method for counting phytohemagglutinin-stimulated lymphocytes. Blood. 1967; 29(4):Suppl:628-39. View

14.

FARNES P, Barker B, Brownhill L, FANGER H . MITOGENIC ACTIVITY IN PHYTOLACCA AMERICANA (POKEWEED). Lancet. 1964; 2(7369):1100-1. DOI: 10.1016/s0140-6736(64)92616-9. View

15.

Nowell P . Phytohemagglutinin: an initiator of mitosis in cultures of normal human leukocytes. Cancer Res. 1960; 20:462-6. View

16.

Green E, Reible S . Paired moving charges in mitochondrial energy coupling. II. Universality of the principles for energy coupling in biological systems. Proc Natl Acad Sci U S A. 1975; 72(1):253-7. PMC: 432282. DOI: 10.1073/pnas.72.1.253. View

17.

Nowell P, Daniele R, Winger L . Kinetics of human lymphocyte proliferation: proportion of cells responsive to phytohemagglutinin and correlation with E rosette formation. J Reticuloendothel Soc. 1975; 17(1):47-56. View

18.

Spector I, Palfrey C, LITTAUER U . Enhancement of the electrical excitability of neuroblastoma cells by valinomycin. Nature. 1975; 254(5496):121-4. DOI: 10.1038/254121a0. View

19.

Hinkle M, Van Der Kloot W . The effects of valinomycin on striated muscles of the frog and the crayfish. Comp Biochem Physiol A Comp Physiol. 1973; 46(2):269-78. DOI: 10.1016/0300-9629(73)90417-9. View

20.

Rasmussen H . Cell communication, calcium ion, and cyclic adenosine monophosphate. Science. 1970; 170(3956):404-12. DOI: 10.1126/science.170.3956.404. View