Tài liệu Báo cáo khoa học: Osmosensing and signaling in the regulation of mammalian cell function

MINIREVIEW

Osmosensing and signaling in the regulation

of mammalian cell function

Freimut Schliess, Roland Reinehr and Dieter Ha¨ussinger

Clinic for Gastroenterology, Hepatology and Infectiology, Heinrich-Heine-University, Du¨ sseldorf, Germany

Introduction

Sudden exposure of cells to hypo- or hyperosmotic

solutions induces a rapid osmotic swelling or shrink￾age, respectively. Extensive swelling or shrinkage is

counteracted by induction of a regulatory volume

decrease (RVD) or increase, respectively [1–3]. Most

hypoosmotically swollen cells perform RVD by a

release of inorganic ions, including K+, Na+, Cl–

, and

HCO3

– and organic osmolytes (e.g. taurine, betaine).

Hyperosmotic regulatory volume increase (RVI) at a

short-term time scale is performed by activation of

electrolyte uptake (e.g. via Na+ ⁄ K+ ⁄ 2Cl– cotransport

and Na+ ⁄ H+ exchange). Long-term adaption to

hyperosmolarity includes an isoosmotic exchange of

inorganic ions against compatible organic osmolytes,

which preserve protein function even at high concen￾trations [4].

Transport systems involved in RVD or RVI can be

activated also by hormones, substrates, second messen￾gers and oxidative stress under isoosmotic conditions.

In these cases, moderate and well-tolerated cell volume

changes are created. For example, insulin produces

a phosphoinositide 3-kinase (PI 3-kinase)-dependent

hepatocyte swelling by inducing a net accumulation of

ions inside the cell, which results from a concerted

activation of Na+ ⁄ H+ exchange, Na+ ⁄ K+ ⁄ 2Cl– sym￾port and the Na+ ⁄ K+-ATPase [5].

In the early 1990s, it was recognized, that cell vol￾ume changes trigger signals involved in the regulation

of metabolism, gene expression and the susceptibility

to different kinds of stress [6]. For example, the inhibi￾tion of autophagic proteolysis by insulin, glutamine

and ethanol in the perfused liver critically depends on

the degree of hepatocyte swelling induced by these

stimuli and can be mimicked by hypoosmotic swelling

Keywords

apoptosis; bile acids; CD95; cell volume;

epidermal growth factor; insulin; integrins;

osmolytes; oxidative stress; proliferation

Correspondence

F. Schliess, Heinrich-Heine-Universita¨t,

Universita¨tsklinikum, Klinik fu¨r

Gastroenterologie und Infektiologie,

Moorenstrasse 5, D-40225 Du¨ sseldorf,

Germany

Fax: +49 211 81 17517

Tel: +49 211 81 18941

E-mail: [email protected]

(Received 2 July 2007, accepted 29 August

2007)

doi:10.1111/j.1742-4658.2007.06100.x

Volume changes of mammalian cells as induced by either anisoosmolarity

or under isoosmotic conditions by hormones, substrates and oxidative

stress critically contribute to the regulation of metabolism, gene expression

and the susceptibility to stress. Osmosensing (i.e. the registration of cell

volume) triggers signal transduction pathways towards effector sites (osmo￾signaling), which link alterations of cell volume to a functional outcome.

This minireview summarizes recent progress in the understanding of how

osmosensing and osmosignaling integrate into the overall context of growth

factor signaling and the execution of apoptotic programs.

Abbreviations

EGF, epidermal growth factor; MAPK, mitogen-activated protein kinase; PI 3-kinase, phosphoinositide 3-kinase; RGD, arginine-glycine￾aspartic acid; ROS, reactive oxygen species; RVD, regulatory volume decrease; RVI, regulatory volume increase.

FEBS Journal 274 (2007) 5799–5803 ª 2007 The Authors Journal compilation ª 2007 FEBS 5799