ER stress and ER stress-induced apoptosis are activated in gastric SMCs in diabetic rats

World J Gastroenterol. 2014 Jul 7;20(25):8260-7. doi: 10.3748/wjg.v20.i25.8260.

Abstract

Aim: To investigate the gastric muscle injury caused by endoplasmic reticulum (ER) stress in rats with diabetic gastroparesis.

Methods: Forty rats were randomly divided into two groups: a control group and a diabetic group. Diabetes was induced by intraperitoneal injection of 60 mg/kg of streptozotocin. Gastric emptying was determined at the 4(th) and 12(th) week. The ultrastructural changes in gastric smooth muscle cells (SMCs) were investigated by transmission electron microscopy. TdT-mediated dUTP nick end labeling (TUNEL) assay was performed to assess apoptosis of SMCs. Expression of the ER stress marker, glucose-regulated protein 78 (GRP78), and the ER-specific apoptosis mediator, caspase-12 protein, was determined by immunohistochemistry.

Results: Gastric emptying was significantly lower in the diabetic rats than in the control rats at the 12(th) wk (40.71% ± 2.50%, control rats vs 54.65% ± 5.22%, diabetic rats; P < 0.05). Swollen and distended ER with an irregular shape was observed in gastric SMCs in diabetic rats. Apoptosis of gastric SMCs increased in the diabetic rats in addition to increased expression of GRP78 and caspase-12 proteins.

Conclusion: ER stress and ER stress-mediated apoptosis are activated in gastric SMCs in diabetic rats with gastroparesis.

Keywords: Apoptosis; Caspase-12; Diabetic gastroparesis; Endoplasmic reticulum stress; glucose-regulated protein 78 kD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Caspase 12 / metabolism
  • Diabetes Mellitus, Experimental / complications*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Endoplasmic Reticulum / metabolism
  • Endoplasmic Reticulum / ultrastructure*
  • Endoplasmic Reticulum Stress*
  • Gastric Emptying
  • Gastric Mucosa / metabolism
  • Gastroparesis / etiology*
  • Gastroparesis / metabolism
  • Gastroparesis / pathology
  • Gastroparesis / physiopathology
  • Heat-Shock Proteins
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Microscopy, Electron, Transmission
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / ultrastructure*
  • Rats, Wistar
  • Stomach / physiopathology
  • Stomach / ultrastructure*
  • Time Factors

Substances

  • GRP78 protein, rat
  • Heat-Shock Proteins
  • Casp12 protein, rat
  • Caspase 12