Premium
Effect of Methyglyoxal and Curcumin on PC12 and RINm5f Cells
Author(s) -
Castro Victoria Puccini,
Keys Steven,
Su Jing,
Mungre Sue
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.774.21
Subject(s) - oxidative stress , unfolded protein response , curcumin , programmed cell death , apoptosis , chemistry , chop , cell culture , nitric oxide synthase , pharmacology , caspase 3 , nitric oxide , endocrinology , medicine , biology , biochemistry , genetics
Uncontrolled diabetes can lead to several serious complications such as kidney failure, atherosclerosis and neuropathy. Methylglyoxal (MG), a highly reactive compound derived from glucose and fructose metabolism has been implicated as the causative agent in these complications. Our work with neuronal PC12 cells has shown that MG treatment caused death of 60% of PC12 cells within 24 hours. It also increased the activity of inducible nitric oxide synthase (iNOS) and caspase‐3, suggesting that MG causes apoptotic cell death via oxidative stress. Curcumin, an antioxidant from the spice Curcuma longa , prevented cell death and the inhibited the activity of iNOS and caspase‐3. Oxidative stress is also reported to cause ER stress resulting in unfolded protein response (UPR). To determine whether it occurs in PC12 cells, we studied the effect of MG on the expression of CHOP and Bip, genes involved in UPR using qPCR. MG treatment increased the expression of CHOP by 20 fold and that of BiP by 10 fold. Treatment with curcumin partially reversed the effect, indicating that MG caused ER stress in PC12 cells. We extended these studies to RINm5f, a pancreatic beta cell line. Diabetic conditions have been reported to cause dysfunction of beta cells. Our preliminary studies show that there was 60–70% death in MG treated RINm5f cells, suggesting that similar oxidative stress/ER stress mechanism may be involved. Support or Funding Information COR grant from Northeastern Illinois University