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Thy‐1‐Mediated phosphatidylinositol turnover in cultured rat glomerular mesangial cell
Author(s) -
NarisawaSaito Mako,
Kimura Satoshi,
Fujiwara Naoshi,
Oite Takashi,
Shimoji Koki,
Shimizu Fujio
Publication year - 1996
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199609)168:3<705::aid-jcp23>3.0.co;2-w
Subject(s) - phosphatidylinositol , microbiology and biotechnology , mesangial cell , chemistry , endocrinology , medicine , biology , andrology , signal transduction , kidney
Thy‐1 glycoprotein is expressed in rat glomerular mesangial cells, and anti‐Thy‐1 nephritis induced by anti‐Thy‐1 antibodies is a model of human renal diseases. In this study, we examined Thy‐1‐mediated biological reactions in cultured rat glomerular mesangial cells utilizing two anti‐Thy‐1 monoclonal antibodies (mAbs), 1‐22‐3 and OX‐7. Incubation of the cells with these mAbs resulted in increased inositol trisphosphate (IP 3 ) levels. The rise in IP 3 produced by mAb 1‐22‐3 was greater than that produced by mAb OX‐7 at the same dose. Incubation of mesangial cells with these mAbs resulted in an increase in the intracellular free calcium concentration ([Ca 2+ ]i). mAb 1‐22‐3 induced a sustained increase in [Ca 2+ ]i, while that induced by mAb OX‐7 lasted 1‐2 min, then decreased to the basal level. An transient increase in [Ca 2+ ]i was also observed in Ca 2+ ‐free medium, indicating that these [Ca 2+ ]i increases are due to release of Ca 2+ from internal stores by IP 3 without calcium flux across cell membrane. When cells were pretreated with protein tyrosine kinase (PTK) inhibitors (herbimycin A or genistein), Thy‐1‐mediated increases in [Ca 2+ ]i were inhibited. These data suggest that Thy‐1 induces the production of IP 3 (including inositol 1,4,5‐triphosphate, an intracellular Ca 2+ ‐releasing factor) and that PTKs may contribute to the Thy‐1‐mediated elevation of [Ca 2+ ]i which presumably results from phospholipase C activation following Thy‐1‐mediated signaling in rat mesangial cells. © 1996 Wiley‐Liss, Inc.