APOPTOSIS INDUCED BY IL-2 WITHDRAWAL IS ASSOCIATED WITH AN INTRACELLULAR ACIDIFICATION

被引：58
作者：
REBOLLO, A [1 ]
GOMEZ, J [1 ]
DEARAGON, AM [1 ]
LASTRES, P [1 ]
SILVA, A [1 ]
PEREZSALA, D [1 ]
机构：
[1] CSIC,CTR INVEST BIOL,E-28006 MADRID,SPAIN
来源：
EXPERIMENTAL CELL RESEARCH | 1995年 / 218卷 / 02期
关键词：
D O I：
10.1006/excr.1995.1195
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
It is known that phorbol esters can protect IL-2-dependent lymphocytes against apoptosis induced by IL-2 withdrawal. However, the mechanism of this effect remains unclear. In this article we show that apoptosis induced by IL-2 withdrawal in the CTLL-2 cell line correlates with a decrease in intracellular pH (pH(i)). Supplementing the incubation medium with phorbol esters during IL-2 deprivation protects CTLL-2 cells against both apoptosis and intracellular acidification. Interestingly, IL-4 also supports short-term cell survival and maintenance of normal pH(i). The protein kinase inhibitor staurosporine prevents the protective effects of IL-2, PMA, and IL-4 on apoptosis and intracellular acidification. In contrast, inhibition of the Na+/H+ antiporter by 5-N-ethyl-N-isopropyl amiloride reverts the protective effects of PMA and IL-4, but only weakly affects IL-8-mediated suppression of apoptosis. Taken together, these results indicate that intracellular acidification may be an important event during apoptosis induced by IL-2 deprivation in the CTLL-2 cell line. Moreover, they suggest a key role for protein kinase C activation both in the maintenance of pH(i) and in the suppression of apoptosis, through mechanisms which rely on the activation of the Na+/H+ antiporter to a different extent, depending on the rescuing factor employed. (C) 1995 Academic Press, Inc.
引用
收藏
页码：581 / 585
页数：5
相关论文
共 31 条
  • [1] Ucker D.S., New Biol., 3, pp. 103-107, (1991)
  • [2] Collins M.K.L., Lopez Rivas A., Trends Biochem. Sei., 18, pp. 307-309, (1993)
  • [3] Gerchenson L.E., Roteilo R.J., FASEB J., 6, pp. 2450-2455, (1992)
  • [4] Peitsch M.C., Polzas B., Stephan H., Crompton T., McDonald H.R., Mannherz H.G., Tschopp J., EMBO J., 12, pp. 371-377, (1993)
  • [5] Barry M.A., Eastman A., Arch. Biochem. Biophys., 300, pp. 440-450, (1993)
  • [6] Duke R.C., Cohen J.J., Lymphokine Res, 5, pp. 289-292, (1986)
  • [7] Willians G.T., Smith C.A., Sopooncer E., Dexter T.M., Taylor D.R., Nature, 343, pp. 76-78, (1990)
  • [8] Nieto M.A., Lopez-Rivas A., J. Immunol., 143, pp. 4166-4170, (1989)
  • [9] Rajotte D., Haddad P., Haman A., Cragoe E.J., Hoang T., J. Biol. Chem., 267, pp. 9980-9987, (1992)
  • [10] Lee S., Christakos S., Small M.B., Curr. Opin. Cell Biol., 5, pp. 286-291, (1993)
1234