The decreased expression of thioredoxin-1 in brain of mice with experimental autoimmune myasthenia gravis

Neuromuscul Disord. 2014 Aug;24(8):726-35. doi: 10.1016/j.nmd.2014.05.001. Epub 2014 May 13.

Abstract

Myasthenia gravis (MG) is an autoimmune disease caused by circulating antibodies that block acetylcholine receptor (AchR) at the neuromuscular junction. There is the cognitive and memory impairment in patients with MG. However, the molecular mechanisms underlying the alteration of central nervous system in MG remain unknown. In the present study, we found that the level of malondialdehyde (MDA) was increased in the brain of experimental autoimmune myasthenia gravis (EAMG). Furthermore, the expression of thioredoxin-1 (Trx-1) and the activity of cAMP response element-binding protein (CREB) were significantly decreased in frontal lobe and hippocampus of mice with EAMG. We also found that the expression of pro-apoptotic C/EBP homologous protein (CHOP) was increased in the frontal lobe and hippocampus of mice. However, the expressions of glucose regulated protein 78 (GRP78/Bip) was not changed in same areas. Inversely, the expressions of pro-caspase-12, pro-caspase-3 and pro-caspase-9 were decreased. These data indicate that Trx-1 mediated endoplasmic reticulum and mitochondria pathways are involved in brain damage in MG. Trx-1 may be a pivotal target for brain protective treatment in MG.

Keywords: C/EBP homologous protein; Endoplasmic reticulum; Mitochondria; Myasthenia gravis; Thioredoxin-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Caspase 12 / metabolism
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Endoplasmic Reticulum Chaperone BiP
  • Female
  • Frontal Lobe / metabolism*
  • Heat-Shock Proteins / metabolism
  • Hippocampus / metabolism*
  • Malondialdehyde / metabolism
  • Mice, Inbred C57BL
  • Mitochondria / physiology
  • Muscle Weakness / physiopathology
  • Myasthenia Gravis, Autoimmune, Experimental / metabolism*
  • Myasthenia Gravis, Autoimmune, Experimental / physiopathology
  • Thioredoxins / metabolism*
  • Transcription Factor CHOP / metabolism

Substances

  • Creb1 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • Ddit3 protein, mouse
  • Endoplasmic Reticulum Chaperone BiP
  • Heat-Shock Proteins
  • Hspa5 protein, mouse
  • Txn1 protein, mouse
  • Transcription Factor CHOP
  • Malondialdehyde
  • Thioredoxins
  • Casp12 protein, mouse
  • Casp3 protein, mouse
  • Casp9 protein, mouse
  • Caspase 12
  • Caspase 3
  • Caspase 9