Issue 21, 2021

A dipeptidyl peptidase IV inhibitory peptide relieves palmitic acid-induced endoplasmic reticulum stress in HepG2 cells independent of inhibiting dipeptidyl peptidase IV activity

Abstract

The peptide VLATSGPG (VLA) is known to inhibit dipeptidyl peptidase IV (DPP-IV), although its mechanism in relieving endoplasmic reticulum (ER) stress is unclear. In this study, we found that treating HepG2 cells with 1.0 mM VLA reduced DPP-IV activity by 73.7 ± 4.8% without changing the DPP-IV mRNA expression level. In addition, 1.0 and 0.5 mM VLA alleviated palmitic acid (PA)-induced cell death and intracellular calcium imbalances. The levels of apoptosis-related proteins (caspase-3, caspase-9, and CHOP) were reduced by VLA treatment, which was presumed to be related to ER stress. Further studies confirmed that VLA alleviated PA-induced morphological damage to the ER and reduced the levels of the ER stress marker proteins (BIP, p-PERK, and p-IRE1α). VLA alleviated PA-induced ER stress in HepG2 cells independent of DPP-IV enzymatic activity inhibition. These findings have implications for developing novel treatment approaches for liver diseases caused by ER stress.

Graphical abstract: A dipeptidyl peptidase IV inhibitory peptide relieves palmitic acid-induced endoplasmic reticulum stress in HepG2 cells independent of inhibiting dipeptidyl peptidase IV activity

Supplementary files

Article information

Article type
Paper
Submitted
15 Jul 2021
Accepted
14 Sep 2021
First published
20 Sep 2021

Food Funct., 2021,12, 10773-10782

A dipeptidyl peptidase IV inhibitory peptide relieves palmitic acid-induced endoplasmic reticulum stress in HepG2 cells independent of inhibiting dipeptidyl peptidase IV activity

R. Jin, H. Ren, M. Liao, J. Shang, D. Wang, M. Li and N. Liu, Food Funct., 2021, 12, 10773 DOI: 10.1039/D1FO02283K

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