Lysophosphatidic acid: a novel growth and survival factor for renal proximal tubular cells

被引:79
作者
Levine, JS
Koh, JS
Triaca, V
Lieberthal, W
机构
关键词
apoptosis; phosphatidylinositol; 3-kinase; phospholipids;
D O I
10.1152/ajprenal.1997.273.4.F575
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Lysophosphatidic acid (LPA) is the smallest and structurally simplest of all glycerophospholipids. LPA is a normal constituent of serum and binds with high affinity to albumin while retaining its biological activity. The effects of LPA are pleiotropic and range from mitogenesis to stress fiber formation. In this report, we demonstrate two novel functions for LPA. LPA acts as a survival factor to inhibit apoptosis of primary cultures of mouse renal proximal tubular (MPT) cells. LPA also acts as a potent mitogen for MPT cells. The ability of LPA to act as both a survival factor and a mitogen is mediated by the lipid kinase phosphatidylinositol 3-kinase (PI3K), since these activities were completely blocked by wortmannin or LY-294002, two structurally dissimilar inhibitors of PI3K. The identification of LPA as a proliferative and anti-apoptotic factor suggests a potential role for this lipid mediator during the injury and/or recovery phases following tubular damage.
引用
收藏
页码:F575 / F585
页数:11
相关论文
共 32 条
  • [11] LIEB, 1996, AM J PHYSIOL, V270, pF700
  • [12] Mechanisms of apoptosis and its potential role in renal tubular epithelial cell injury
    Lieberthal, W
    Levine, JS
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY, 1996, 271 (03): : F477 - F488
  • [13] THE EXTRACELLULAR-MATRIX AS A CELL-SURVIVAL FACTOR
    MEREDITH, JE
    FAZELI, B
    SCHWARTZ, MA
    [J]. MOLECULAR BIOLOGY OF THE CELL, 1993, 4 (09) : 953 - 961
  • [14] LYSOPHOSPHATIDIC ACID SIGNALING
    MOOLENAAR, WH
    [J]. CURRENT OPINION IN CELL BIOLOGY, 1995, 7 (02) : 203 - 210
  • [15] OKADA T, 1994, J BIOL CHEM, V269, P3563
  • [16] AN ESSENTIAL ROLE FOR RHO, RAC, AND CDC42 GTPASES IN CELL-CYCLE PROGRESSION THROUGH G(1)
    OLSON, MF
    ASHWORTH, A
    HALL, A
    [J]. SCIENCE, 1995, 269 (5228) : 1270 - 1272
  • [17] INCREASED MEMBRANE-PERMEABILITY OF APOPTOTIC THYMOCYTES - A FLOW CYTOMETRIC STUDY
    ORMEROD, MG
    SUN, XM
    SNOWDEN, RT
    DAVIES, R
    FEARNHEAD, H
    COHEN, GM
    [J]. CYTOMETRY, 1993, 14 (06): : 595 - 602
  • [18] Price BE, 1996, J IMMUNOL, V157, P2201
  • [19] SOCIAL CONTROLS ON CELL-SURVIVAL AND CELL-DEATH
    RAFF, MC
    [J]. NATURE, 1992, 356 (6368) : 397 - 400
  • [20] THE SMALL GTP-BINDING PROTEIN RHO REGULATES THE ASSEMBLY OF FOCAL ADHESIONS AND ACTIN STRESS FIBERS IN RESPONSE TO GROWTH-FACTORS
    RIDLEY, AJ
    HALL, A
    [J]. CELL, 1992, 70 (03) : 389 - 399