Methods for studying redox cycling of thioredoxin in mediating preconditioning-induced survival genes and proteins.
Recent advances in molecular biology provide methods and tools for studying cell signaling pathways underlying hormetic mechanisms produced by radiation hormesis, ischemic, remote ischemic, and chemical preconditioning as well as withholding of nutrients and/or trophic factors. Most of the proposed key signaling pathways of hormetic mechanisms remain to be elucidated. For the investigation of possible role of thiol redox signaling systems in hormesis, a serum deprivation preconditioned human cell model, free radical assays, and molecular biological methods are employed for studying whether free radicals, the NO-cGMP-PKG cell signaling pathway, and the redox protein thioredoxin (Trx) play any roles in the hormetic mechanism against cytotoxicity caused by serum deprivation and also neurotoxin 1-methyl-4-phenyltetrahydropyridinium ion (MPP(+)). This NO-dependent cell signaling pathway of the redox protein Trx may play a key role in the cellular protective mechanism of several potential neuroprotective agents such as S-nitrosoglutathione (GSNO), 17beta-estradiol, selegiline as well as ebeselen, sildenafil, and rasagiline. Consistently, exogenously administrated Trx (<1 microM) provides a concentration-dependent protection for human neuroblasts against MPP(+)-induced oxidative injury. This newly discovered role of the redox protein of Trx in preconditioning-induced cell signaling and protection could lead to the development of new lead compounds for upregulation of Trx and related thiol redox proteins for cell survival, repair, proliferation, and neuronal plasticity.
Chiueh
Chuang C
CC
Division of Clinical Pharmacy, School of Pharmacy and Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan.
D045784:Abietanes; D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D005796:Genes / Q000502:physiology*; D056726:Genetic Association Studies; D006801:Humans; D008954:Models, Biological; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013879:Thioredoxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D045784:Abietanes; D011506:Proteins; D013879:Thioredoxins; C045490:horminone