Format

Send to

Choose Destination
Life Sci. 2014 May 8;103(1):15-24. doi: 10.1016/j.lfs.2014.03.007. Epub 2014 Mar 17.

4-Phenylbutyric acid suppresses inflammation through regulation of endoplasmic reticulum stress of endothelial cells stimulated by uremic serum.

Author information

1
Institute of Nephrology of Chongqing and Department of Nephrology, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, PR China.
2
Institute of Nephrology of Chongqing and Department of Nephrology, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, PR China. Electronic address: fxb12@aliyun.com.

Abstract

AIMS:

Endoplasmic reticulum (ER) stress is involved in the pathogenesis of atherosclerosis (AS). Endothelial cell (EC) dysfunction and monocyte migration to the subendothelium are considered to be essential manifestations of AS. We conducted this study to determine whether ER stress was involved in uremic serum-induced EC dysfunction and whether the regulation of ER stress using a chemical chaperone 4-phenylbutyric acid (4-PBA) had a preventative effect.

MAIN METHODS:

Human umbilical vein endothelial cells (HUVECs) were divided into 4 groups: a control serum group (C.S), a uremic serum group (U.S), a uremic serum plus 4-PBA (5mM) treatment group (4-PBA), and a uremic serum plus pyrrolidine dithiocarbamate (PDTC:50 μM) treatment group (PDTC).

KEY FINDINGS:

Lower concentrations of uremic serum (<10%) facilitated the proliferation of HUVECs. In contrast, the proliferative capability of HUVECs was gradually decreased when we continuously increased the concentration of uremic serum. Compared with C.S, HUVEC incubation with uremic serum had high expression levels of GRP78, p-PERK, NF-κB, MCP-1, and VEGF. THP-1 migration was markedly higher than C.S over the indicated time. These alterations were inhibited by the administration of 4-PBA.

SIGNIFICANCE:

These findings suggest that regulation of ER stress coupled with inflammatory activation by 4-PBA would be a promising therapy to reverse the process and development of uremic serum-induced EC dysfunction.

KEYWORDS:

4-Phenylbutyric acid; Atherosclerosis; Chronic renal failure; Endoplasmic reticulum stress; Inflammatory activation

PMID:
24650493
DOI:
10.1016/j.lfs.2014.03.007
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center