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Cited by 270

The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.

Increases of intracellular magnesium promote glycodeoxycholate-induced apoptosis in rat hepatocytes.

Open access
Patel, T, Bronk, S F, Gores, G J·1994·Journal of Clinical Investigation

Abstract

Retention of bile salts by the hepatocyte contributes to liver injury during cholestasis. Although cell injury can occur by one of two mechanisms, necrosis versus apoptosis, information is lacking regarding apoptosis as a mechanism of cell death by bile salts. Our aim was to determine if the bile salt glycodeoxycholate (GDC) induces apoptosis in rat hepatocytes. Morphologic assessment included electron microscopy and quantitation of nuclear fragmentation by fluorescent microscopy. Biochemical studies included measurements of DNA fragmentation, in vitro endonuclease activity, cytosolic free Ca2+ (Cai2+), and cytosolic free Mg2+ (Mgi2+). Morphologic studies demonstrated typical features of apoptosis in GDC (50 microM) treated cells. The "ladder pattern" of DNA fragmentation was also present in DNA obtained from GDC-treated cells. In vitro endonuclease activity was 2.5-fold greater with Mg2+ than Ca2+. Although basal Cai2+ values did not change after addition of GDC, Mgi2+ increased twofold. Incubation of cells in an Mg(2+)-free medium prevented the rise in Mgi2+ and reduced nuclear and DNA fragmentation. In conclusion, GDC induces apoptosis in hepatocytes by a mechanism promoted by increases of Mgi2+ with stimulation of Mg(2+)-dependent endonucleases. These data suggest for the first time that changes of Mgi2+ may participate in the program of cellular events culminating in apoptosis.

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Metadata

Authors
Patel, T., Bronk, S. F., & Gores, G. J.
Venue
Journal of Clinical Investigation
Published
1994-12-01
Volume
94
Issue
6
Pages
2183-2192
ISSN
0021-9738 (ISSN-L)
OpenAlex
W1976773018
Cited by
270
References
50
FWCI
2.45
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Increases of intracellular magnesium promote glycodeoxycholate-induced apoptosis in rat hepatocytes. https://app.cochat.ai/papers/10.1172/jci117579
The paper
Patel, T., Bronk, S. F., & Gores, G. J. (1994). Increases of intracellular magnesium promote glycodeoxycholate-induced apoptosis in rat hepatocytes. Journal of Clinical Investigation. https://doi.org/10.1172/jci117579

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