Inhibition of the Na+/H+-antiporter by theophylline in growth-arrested monkey kidney cells

Mungre, Shubhangee; Renz, Christopher; Rundell, Kathleen

doi:10.1016/0014-4827(91)90563-a

Experimental Cell Research

1991

DOI: 10.1016/0014-4827(91)90563-a

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Inhibition of the Na+/H+-antiporter by theophylline in growth-arrested monkey kidney cells

Shubhangee Mungre

Christopher Renz

Kathleen Rundell

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1991

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Cited by 3 publications

(1 citation statement)

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“…An early system used to study growth promotion by small-t is its ability to confer resistance to growth arrest elicited by the methylxanthine compound theophylline (52), a known inhibitor of cyclic AMP phosphodiesterase. Surprisingly, theophylline-mediated growth arrest correlates not with increased levels of intracellular cyclic AMP (47) but rather with inhibition of the Na ϩ /H ϩ antiporter (38). The antiporter, or Na ϩ /H ϩ exchanger (NHE), represents a family of mitogen-responsive ion transporters and regulators of intracellular pH (5,16,72).…”

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confidence: 99%

Cell Cycle Progression in Monkey Cells Expressing Simian Virus 40 Small t Antigen from Adenovirus Vectors

Howe

Gaillard

Bennett

et al. 1998

J Virol

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The simian virus 40 small t antigen (small-t) is required for optimal viral replication and transformation, especially during the infection of nondividing cells, suggesting that the function of small-t is to promote cell cycle progression. The mechanism through which small-t promotes cell growth reflects, in part, its binding and inhibition of protein phosphatase 2A (PP2A). The use of recombinant adenoviruses allows small-t expression in a majority of cells in a population, thus providing a convenient source of cells for biochemical analyses. In monkey kidney CV1 cells, small-t expressed from these adenovirus vectors activated the mitogen-activated protein kinase (MAPK) pathway, induced JNK activity, and increased AP-1 DNA-binding activity, all in a PP2A-dependent manner. Expression of small-t also caused an increase in the phosphorylation of the Na+/H+ antiporter, a mitogen-activated ion exchanger whose activity correlates with its phosphorylation. At least part of the antiporter phosphorylation induced by small-t reflected activation of the MAPK pathway, as suggested by results of assays using a chemical inhibitor of the MAPK-activating kinase, MEK. Finally, small-t expression from adenovirus vectors promoted efficient cell cycle progression by growth-arrested cells. These vectors should facilitate further analysis of effects of small-t on cell cycle mediators.

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mentioning

confidence: 99%

Cell Cycle Progression in Monkey Cells Expressing Simian Virus 40 Small t Antigen from Adenovirus Vectors

Howe

Gaillard

Bennett

et al. 1998

J Virol

Self Cite

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Simian virus 40 small-t antigen stimulates viral DNA replication in permissive monkey cells

Cicala¹,

Avantaggiati²,

Graessmann³

et al. 1994

J Virol

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The simian virus 40 (SV40) large-T antigen is essential for SV40 DNA replication and for late viral gene expression, but the role of the SV40 small-t antigen in these processes is still unclear. We have previously demonstrated that small t inhibits SV40 DNA replication in vitro. In this study, we investigated the effect of small t on SV40 replication in cultured cells. CV1 monkey cell infection experiments indicated that mutant viruses that lack small t replicate less efficiently than the wild-type virus. We next microinjected CV1 cells with SV40 DNA with and without purified small-t protein and analyzed viral DNA replication efficiency by Southern blotting. Replication of either wild-type SV40 or small-t deletion mutant DNA was increased three- to fivefold in cells coinjected with purified small t. Thus, in contrast to our in vitro observation, small t stimulated viral DNA replication in vivo. This result suggests that small t has cellular effects that are not detectable in a reconstituted in vitro replication system. We also found that small t stimulated progression of permissive monkey cells--but not of nonpermissive rodent cells--from G0-G1 to the S phase of the cell cycle, possibly leading to an optimal intracellular environment for viral replication.

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Influence of adenosine receptor blockade on renal function and renal autoregulation.

Ibarrola

Inscho

Vari

et al. 1991

Journal of the American Society of Nephrology

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Experiments were conducted in anesthetized dogs to evaluate the effects of adenosine receptor blockade on renal function and on autoregulation of total RBF and outer cortical blood flow. After control measurements, the adenosine receptor antagonist, 1,3-dipropyl-8-p-sulfophenylxanthine (PSPX) was infused intrarenally for 45 min at 2 or 6 microM/min. Responses to PSPX were compared with those obtained during infusions of either aminophylline or theophylline. PSPX infusion led to substantial increases in urine flow and sodium excretion (four- to fivefold). RBF increased significantly; however, outer cortical blood flow and GFR were not significantly altered. PRA increased twofold during PSPX infusion. The vasoconstrictor responses to bolus injections of 2-chloroadenosine (100 mumol) were attenuated by 58 and 86% during the low and high doses of PSPX and to a lesser extent with aminophylline/theophylline infusions. At renal arterial pressures above the inflection point, the slope of the average pressure-flow relationship during PSPX infusion was close to zero and was not significantly different from control. Similarly, autoregulatory capability was not altered during infusions of theophylline or aminophylline. These data provide further evidence that endogenous adenosine contributes substantially to the control of renin release but only modestly to the control of RBF and GFR and to renal autoregulatory capability. The natriuretic responses during adenosine blockade, which occurred in the face of elevated renin levels, support the hypothesis that endogenous adenosine enhances tubular sodium reabsorption rate.

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Inhibition of the Na+/H+-antiporter by theophylline in growth-arrested monkey kidney cells

Cited by 3 publications

References 18 publications

Cell Cycle Progression in Monkey Cells Expressing Simian Virus 40 Small t Antigen from Adenovirus Vectors

Cell Cycle Progression in Monkey Cells Expressing Simian Virus 40 Small t Antigen from Adenovirus Vectors

Simian virus 40 small-t antigen stimulates viral DNA replication in permissive monkey cells

Influence of adenosine receptor blockade on renal function and renal autoregulation.

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