Glycyrrhizin attenuates HMGB1-induced hepatocyte apoptosis by inhibiting the p38-dependent mitochondrial pathway.

Abstract

AIM:

To examine how high-mobility group box 1 (HMGB1) regulates hepatocyte apoptosis and, furthermore, to determine whether glycyrrhizin (GL), a known HMGB1 inhibitor, prevents HMGB1-induced hepatocyte apoptosis.

METHODS:

A human hepatocellular carcinoma cell line stably transfected with a bile acid transporter (Huh-BAT cells), were used in this study. Apoptosis was quantified using 4',6-diamidino-2-phenylindole dihydrochloride staining and the APO Percentage apoptosis assay, and its signaling cascades were explored by immunoblot analysis. Kinase signaling was evaluated by immunoblotting and by using selective inhibitors. It is also tried to identify hepatocyte apoptosis affected by the HMGB1 inhibitor, GL.

RESULTS:

HMGB1 increased cellular apoptosis in Huh-BAT cells. HMGB1 led to increased cytochrome c release from mitochondria into the cytosol, and induced the cleavage of procaspase 3. However, it did not affect the activation of caspase 8. HMGB1-induced caspase 3 activation was significantly attenuated by the p38 inhibitor SB203580. GL significantly attenuated HMGB1-induced hepatocyte apoptosis. GL also prevented HMGB1-induced cytochrome c release and p38 activation in Huh-BAT cells.

CONCLUSION:

The present study demonstrated that HMGB1 promoted hepatocyte apoptosis through a p38-dependent mitochondrial pathway. In addition, GL had an anti-apoptotic effect on HMGB1-treated hepatocytes.

• Authors: Geum-Youn Gwak, Tae Gun Moon, Dong Ho Lee, Byung Chul Yoo
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 18 Issue 7 Pg. 679-84 (Feb 21 2012) ISSN: 2219-2840 [Electronic] United States
• PMID: 22363140 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• HMGB1 Protein
• Glycyrrhizic Acid
• p38 Mitogen-Activated Protein Kinases

Topics

• Anti-Inflammatory Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Glycyrrhizic Acid (pharmacology)
• HMGB1 Protein (antagonists & inhibitors, metabolism)
• Hepatocytes (cytology, drug effects, physiology)
• Humans
• Mitochondria (drug effects, metabolism)
• Signal Transduction (drug effects)
• p38 Mitogen-Activated Protein Kinases (metabolism)