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Changes in glutathione homeostasis during liver regeneration in the rat
Author(s) -
Huang ZongZhi,
Li Hongyan,
Cai Jiaxin,
Kuhlenkamp John,
Kaplowitz Neil,
Lu Shelly C.
Publication year - 1998
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510270123
Subject(s) - glutathione , homeostasis , efflux , cysteine , medicine , chemistry , endocrinology , biochemistry , biology , enzyme
We have shown previously that plating primary cultures of rat hepatocytes under low density, which stimulates hepatocytes to shift from the G 0 to the G 1 phase of the cell cycle, resulted in increased levels of glutathione (GSH) and cysteine, and increased activity of γ‐glutamylcysteine synthetase (GCS), the rate‐limiting enzyme in GSH synthesis (Lu et al., Am. J. Physiol. 1992;263:C1181‐C1189). In the current work we examined changes in GSH homeostasis after two‐thirds partial hepatectomy (PH). Male Sprague‐Dawley rats underwent two‐thirds PH or sham operation. GSH, oxidized glutathione (GSSG), cysteine, GSH efflux, DNA synthesis, changes in GCS subunit messenger RNA (mRNA), and protein levels were measured 12 and 24 hours after PH. Both liver GSH and cysteine levels were doubled at 12 hours and remained elevated at 24 hours after PH. GSSG levels also increased, but the ratio of GSH to GSSG levels remained unchanged. The increase in GSH and cysteine levels preceded the increase in DNA synthesis. Sinusoidal GSH efflux was unchanged after two‐thirds PH, but biliary GSH efflux decreased. However, total GSH efflux was minimally altered after two‐thirds PH. The increase in GSH can be largely accounted for by the increase in both cysteine availability and the activity of GCS. The steady‐state mRNA and protein levels of the GCS heavy subunit were increased at 12 hours after PH. The mRNA level of the GCS light subunit was unchanged. In summary, early in the course of liver regeneration the steady‐state hepatic GSH levels double because of an increase in the biosynthesis of GSH.