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1996-02-26
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Document 0741
DOCN M9620741
TI Intracellular calcium release induced by human immunodeficiency virus
type 1 (HIV-1) surface envelope glycoprotein in human intestinal
epithelial cells: a putative mechanism for HIV-1 enteropathy.
DT 9602
AU Dayanithi G; Yahi N; Baghdiguian S; Fantini J; Laboratoire de
Neurobiologie Endocrinologique, CNRS URA 1197,; Universite Montpellier
2, France.
SO Cell Calcium. 1995 Jul;18(1):9-18. Unique Identifier : AIDSLINE
MED/96000449
AB Intracellular Ca2+ ([Ca2+]i) was measured in single human epithelial
intestinal HT-29-D4 cells with the Ca2+ probe Fura-2 and digital imaging
microscopy. Treatment of these cells with HIV-1 surface envelope
glycoprotein gp120 (or a soluble form of its precursor gp160) induced an
important increase of [Ca2+]i. This effect was abolished by
preincubation of the viral glycoprotein with neutralizing antibodies
specific for the V3 domain of gp120. These antibodies inhibited the
binding of both gp120 and gp160 to galactosylceramide (GalCer), the
alternative HIV-1 receptor in HT-29-D4 cells. Moreover, treatment of
HT-29-D4 cells with an anti-GalCer mAb induced an increase in [Ca2+]i
and rendered the cells insensitive to HIV-1 glycoprotein stimulation.
The calcium response resulted from release of Ca2+ from
caffeine-sensitive intracellular stores. Finally, the viral glycoprotein
specifically abrogated the calcium response to the neuropeptide agonist
neurotensin, a stimulator of chloride secretion via inositol
trisphosphate-mediated calcium mobilization. Reciprocally, after
neurotensin stimulation, the cells did not respond to gp120, showing
that neurotensin and gp120 stimulate a common pathway of [Ca2+]i
mobilization. These results suggest that HIV-1 may directly alter ion
secretion in the intestine and thus be the causative agent of the watery
diarrhea associated with HIV-1 infection.
DE Calcium/*METABOLISM Cell Line Enteritis/ETIOLOGY
Epithelium/CYTOLOGY/DRUG EFFECTS/METABOLISM
Galactosylceramides/METABOLISM Gene Products, env/PHARMACOLOGY Human
HIV Envelope Protein gp120/*PHARMACOLOGY HIV Infections/COMPLICATIONS
HIV-1/*PATHOGENICITY Intestines/*DRUG EFFECTS/*METABOLISM
Intracellular Fluid/METABOLISM Protein Precursors/PHARMACOLOGY
Recombinant Proteins/PHARMACOLOGY Support, Non-U.S. Gov't JOURNAL
ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).