Endoplasmic reticulum stress induced autophagy in 6-OHDA-induced Parkinsonian rats

Brain Res Bull. 2019 Mar:146:224-227. doi: 10.1016/j.brainresbull.2019.01.001. Epub 2019 Jan 6.

Abstract

Both endoplasmic reticulum (ER) stress and autophagy involve in the pathological process of Parkinson's disease (PD). But the relationship between them is not clear in PD. A 6-OHDA-induced parkinsonian rat is recognized as a standard model for many years, and it can be used in experimental study. The glucose regulated protein 78 (GRP78) is a master regulator of ER stress, and the C/EBP homologous binding protein (CHOP) is an indicator of the UPR signaling. Besides, the Beclin-1 is also well known as a regulator of autophagy, and P62 is a specific marker to monitor autophagy. Therefore, we investigated the expressions of GRP78, CHOP, Beclin-1 and P62 in 6-OHDA-induced parkinsonian rat. Unilateral 6-OHDA injection into medial forebrain bundle was used except sham-operated rats. The rats were randomly divided into 6 groups: a sham-operated group; a model group; a 3-methyladenine (3-MA) group, administered 3-MA---autophagy inhibitor; a rapamycin group, administered rapamycin---autophagy inducer; a 4-phenylbutyric acids (4-PBA) group, administered 4-PBA---ER stress inhibitor; a tunicamycin (TM) group, administered TM---ER stress inducer. The results showed that the expressions of GRP78, CHOP and Beclin-1 increased, P62 decreased in model group; the expressions of GRP78 and CHOP were unchanged in 3-MA group and rapamycin group; but the expression of Beclin-1 decreased and P62 increased in 4-PBA group, while the expression of Beclin-1 increased and P62 decreased in TM group. These data suggest that ER stress and autophagy occurred in 6-OHDA-induced parkinsonian rat, and ER stress might induce autophagy. The result is important for the pathological mechanism of PD.

Keywords: Autophagy; Endoplasmic reticulum stress; Parkinson’s disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy / drug effects
  • Autophagy / physiology*
  • Beclin-1 / analysis
  • Endoplasmic Reticulum / metabolism
  • Endoplasmic Reticulum Stress / physiology*
  • Female
  • Heat-Shock Proteins / analysis
  • Male
  • Membrane Proteins / metabolism
  • Oxidopamine / pharmacology
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Sequestosome-1 Protein
  • Signal Transduction / drug effects
  • Transcription Factor CHOP / analysis

Substances

  • Apoptosis Regulatory Proteins
  • Beclin-1
  • Ddit3 protein, rat
  • GRP78 protein, rat
  • Heat-Shock Proteins
  • Membrane Proteins
  • Sequestosome-1 Protein
  • Sqstm1 protein, rat
  • Transcription Factor CHOP
  • Oxidopamine