Glucose-induced Changes in Na+/H+ Antiport Activity and Gene Expression in Cultured Vascular Smooth Muscle Cells. Role of Protein Kinase C

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1994 Jun 1

PMID 8201001

Citations 17

Authors

B Williams

R L Howard

Affiliations

Soon will be listed here.

Abstract

Increased Na+/H+ antiport activity has been implicated in the pathogenesis of hypertension and vascular disease in diabetes mellitus. The independent effect of elevated extracellular glucose concentrations on Na+/H+ antiport activity in cultured rat vascular smooth muscle cells (VSMC) was thus examined. Amiloride-sensitive 22Na+ uptake by VSMC significantly increased twofold after 3 and 24 h of exposure to high glucose medium (20 mM) vs. control medium (5 mM). Direct glucose-induced Na+/H+ antiport activation was confirmed by measuring Na(+)-dependent intracellular pH recovery from intracellular acidosis. High glucose significantly increased protein kinase C (PKC) activity in VSMC and inhibition of PKC activation with H-7, staurosporine, or prior PKC downregulation prevented glucose-induced increases in Na+/H+ antiport activity in VSMC. Northern analysis of VSMC poly A+ RNA revealed that high glucose induced a threefold increase in Na+/H+ antiport (NHE-1) mRNA at 24 h. Inhibiting this increase in NHE-1 mRNA with actinomycin D prevented the sustained glucose-induced increase in Na+/H+ antiport activity. In conclusion, elevated glucose concentrations significantly influence vascular Na+/H+ antiport activity via glucose-induced PKC dependent mechanisms, thereby providing a biochemical basis for increased Na+/H+ antiport activity in the vascular tissues of patients with hypertension and diabetes mellitus.

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References

Curran T, Franza Jr B . Fos and Jun: the AP-1 connection. Cell. 1988; 55(3):395-7. DOI: 10.1016/0092-8674(88)90024-4. View

Reaven G . Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988; 37(12):1595-607. DOI: 10.2337/diab.37.12.1595. View

Grinstein S, Rotin D, Mason M . Na+/H+ exchange and growth factor-induced cytosolic pH changes. Role in cellular proliferation. Biochim Biophys Acta. 1989; 988(1):73-97. DOI: 10.1016/0304-4157(89)90004-x. View

Matsumoto H, Sasaki Y . Staurosporine, a protein kinase C inhibitor interferes with proliferation of arterial smooth muscle cells. Biochem Biophys Res Commun. 1989; 158(1):105-9. DOI: 10.1016/s0006-291x(89)80183-4. View

Aviv A, Livne A . The Na+/H+ antiport, cytosolic free Ca2+, and essential hypertension: a hypothesis. Am J Hypertens. 1988; 1(4 Pt 1):410-3. DOI: 10.1093/ajh/1.4.410. View

Sardet C, Franchi A, Pouyssegur J . Molecular cloning, primary structure, and expression of the human growth factor-activatable Na+/H+ antiporter. Cell. 1989; 56(2):271-80. DOI: 10.1016/0092-8674(89)90901-x. View

Salihagic A, Mackovic M, Banfic H, Sabolic I . Short-term and long-term stimulation of Na+-H+ exchange in cortical brush-border membranes during compensatory growth of the rat kidney. Pflugers Arch. 1988; 413(2):190-6. DOI: 10.1007/BF00582530. View

Berk B, Vallega G, Muslin A, Gordon H, Canessa M, Alexander R . Spontaneously hypertensive rat vascular smooth muscle cells in culture exhibit increased growth and Na+/H+ exchange. J Clin Invest. 1989; 83(3):822-9. PMC: 303754. DOI: 10.1172/JCI113964. View

Canessa M, Morgan K, Semplicini A . Genetic differences in lithium-sodium exchange and regulation of the sodium-hydrogen exchanger in essential hypertension. J Cardiovasc Pharmacol. 1988; 12 Suppl 3:S92-8. View

10.

Heasley L, Johnson G . Detection of nerve growth factor and epidermal growth factor-regulated protein kinases in PC12 cells with synthetic peptide substrates. Mol Pharmacol. 1989; 35(3):331-8. View

11.

Canessa M, Adragna N, Solomon H, Connolly T, Tosteson D . Increased sodium-lithium countertransport in red cells of patients with essential hypertension. N Engl J Med. 1980; 302(14):772-6. DOI: 10.1056/NEJM198004033021403. View

12.

Wade J, Stetson D, Lewis S . ADH action: evidence for a membrane shuttle mechanism. Ann N Y Acad Sci. 1981; 372:106-17. DOI: 10.1111/j.1749-6632.1981.tb15464.x. View

13.

Aronson P, Nee J, Suhm M . Modifier role of internal H+ in activating the Na+-H+ exchanger in renal microvillus membrane vesicles. Nature. 1982; 299(5879):161-3. DOI: 10.1038/299161a0. View

14.

Cassel D, Zhuang Y, Glaser L . Vanadate stimulates Na+/H+ exchange activity in A431 cells. Biochem Biophys Res Commun. 1984; 118(2):675-81. DOI: 10.1016/0006-291x(84)91356-1. View

15.

LAllemain G, Paris S, Pouyssegur J . Growth factor action and intracellular pH regulation in fibroblasts. Evidence for a major role of the Na+/H+ antiport. J Biol Chem. 1984; 259(9):5809-15. View

16.

Grinstein S, Cohen S, Rothstein A . Cytoplasmic pH regulation in thymic lymphocytes by an amiloride-sensitive Na+/H+ antiport. J Gen Physiol. 1984; 83(3):341-69. PMC: 2215644. DOI: 10.1085/jgp.83.3.341. View

17.

Tsai C, IVES H, Alpern R, Yee V, Warnock D, RECTOR Jr F . Increased Vmax for Na+/H+ antiporter activity in proximal tubule brush border vesicles from rabbits with metabolic acidosis. Am J Physiol. 1984; 247(2 Pt 2):F339-43. DOI: 10.1152/ajprenal.1984.247.2.F339. View

18.

Hidaka H, Inagaki M, Kawamoto S, Sasaki Y . Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C. Biochemistry. 1984; 23(21):5036-41. DOI: 10.1021/bi00316a032. View

19.

Grinstein S, Goetz J, Rothstein A . 22Na+ fluxes in thymic lymphocytes. II. Amiloride-sensitive Na+/H+ exchange pathway; reversibility of transport and asymmetry of the modifier site. J Gen Physiol. 1984; 84(4):585-600. PMC: 2228749. DOI: 10.1085/jgp.84.4.585. View

20.

Harris R, Seifter J, Brenner B . Adaptation of Na+-H+ exchange in renal microvillus membrane vesicles. Role of dietary protein and uninephrectomy. J Clin Invest. 1984; 74(6):1979-87. PMC: 425385. DOI: 10.1172/JCI111619. View