Cell Volume, the Serum and Glucocorticoid Inducible Kinase 1 and the Liver

Zusammenfassung

Zellschwellung wird durch Freisetzung von Ionen (K⁺-Kanal und/oder Anionen-Kanal-Aktivierung, KCl-Kotransport, gleichzeitige Aktivierung von K⁺/H⁺-Austauscher und Cl^–/HCO₃ ^–-Austauscher) kompensiert, während Zellschrumpfung durch regulatorische Ionenaufnahme ausgeglichen wird (Aktivierung von Na⁺, K⁺, 2Cl^–-Kotransport, Na⁺/H⁺-Austausch bei gleichzeitigem Cl^–/HCO₃ ^–-Austausch und Na⁺-Kanälen). Zusätzlich werden durch Zellschrumpfung organische Osmolyte akkumuliert (z. B.: Myoinositol, Betain, Phosphorylcholin, Taurin). Das Zellvolumen kann den Stoffwechsel stark beeinflussen. Zellschrumpfung aktiviert, Zellschwellung inhibiert die Proteolyse und Glykogenolyse. Außerdem beeinflusst das Zellvolumen die Bildung von Oxidanzien. Des Weiteren spielen diese regulatorischen Mechanismen bei Fibrosierung einzelner Organe eine zentrale Rolle. Ein Signalelement der Zellvolumenregulation ist die Serum- und Glukokortikoidinduzierte Kinase 1 (SGK1), die in der Leber exprimiert und bei Zellschrumpfung hochreguliert wird. Sie stimuliert eine Vielzahl von Ionenkanälen und Transportern, wie bspw. den Na⁺, K⁺, 2Cl^–-Kotransporter und Na⁺/H⁺-Austauscher, und kann zur Fibrosierung beitragen. Zusammenfassend nimmt die SGK1 eine bedeutsame Rolle bei der Leberzellvolumenregulation und konsekutiv dem Leberstoffwechsel ein.

Abstract

In virtually all cells including hepatocytes cell volume regulation is accomplished during cell swelling by cellular ion release (activation of K⁺ channels and/or anion channels, KCl-cotransport, parallel activation of K⁺/H⁺ exchange and Cl^–/HCO₃ ^– exchange) and following cell shrinkage by cellular ion uptake (activation of Na⁺, K⁺, 2Cl^– cotransport, Na⁺/H⁺ exchange in parallel to Cl^–/HCO₃ ^– exchange and Na⁺-channels). Moreover, cell shrinkage triggers the cellular accumulation of organic osmolytes (e. g., myoinositol, betaine, phosphorylcholine, taurine). Cell volume is a powerful regulator of hepatic metabolism. Cell shrinkage stimulates and cell swelling inhibits proteolysis and glycogenolysis. Moreover, cell volume influences the generation of and sensitivity to oxidants. Cell volume regulatory mechanisms furthermore do play a role in fibrosing disease. Kinases stimulating cell volume regulatory mechanisms include the serum and glucocorticoid inducible kinase SGK1, which is expressed in the liver, is genomically up-regulated by cell shrinkage, stimulates a wide variety of channels and transporters including Na⁺, K⁺, 2Cl^– cotransport and Na⁺/H⁺ exchange and is known to participate in the stimulation of fibrosis. Accordingly, excessive SGK1 expression is observed in liver cirrhosis. The case is made that SGK1 participates in the regulation of liver cell volume and thus in the regulation of hepatic metabolism.

Schlüsselwörter

Leber - Zellvolumen - Stoffwechsel

Key words

liver - cell volume - metabolism

References

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