4-phenylbutyric acid attenuates endoplasmic reticulum stress-mediated apoptosis and protects the hepatocytes from intermittent hypoxia-induced injury.

Abstract

PURPOSE:

To investigate the effect of 4-phenylbutyric acid (4-PBA) on intermittent hypoxia (IH)-induced liver cell injury and to clarify the underlying mechanisms.

METHODS:

L02 cells (normal human liver cells) were cultured in normoxic condition or subjected to intermittent hypoxia for 4, 8, and 12 h. A part of hypoxia-treated L02 cells was applied with 4-PBA 1 h before exposure to hypoxia. The effect of 4-PBA on liver injury, hepatocyte apoptosis, endoplasmic reticulum stress (ERS), and PERK-eIFa2-ATF4-CHOP apoptotic pathway was investigated.

RESULTS:

(1) IH caused apoptosis in hepatocyte; (2) IH caused ERS in hepatocyte; (3) IH caused hepatic injury; (4) 4-PBA attenuated IH-induced liver cell injury; (5) 4-PBA protected liver cell from IH-induced apoptosis; (6) 4-PBA suppressed ERS-related apoptotic pathway (PERK-eIFa2-ATF4-CHOP), but did not suppress IH-induced unfold protein reaction (UPR).

CONCLUSIONS:

4-PBA could protect liver cells by suppressing IH-induced apoptosis mediated by ERS, but not by reducing the UPR.

• Authors: Liu Xin, Wu Fan, Du Tingting, Sun Zuoming, Zhang Qiang
• Journal: Sleep & breathing = Schlaf & Atmung (Sleep Breath) Vol. 23 Issue 2 Pg. 711-717 (Jun 2019) ISSN: 1522-1709 [Electronic] Germany
• PMID: 30324548 (Publication Type: Journal Article)

Chemical References

• Phenylbutyrates
• 4-phenylbutyric acid

Topics

• Apoptosis (drug effects)
• Cell Survival (drug effects, physiology)
• Cells, Cultured
• Endoplasmic Reticulum (drug effects, physiology)
• Hepatocytes (drug effects, physiology)
• Humans
• Hypoxia (complications, physiopathology)
• Phenylbutyrates (pharmacology)
• Unfolded Protein Response (drug effects)