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Protective effects of andrographolide analogue AL-1 on ROS-induced RIN-mβ cell death by inducing ROS generation.
- Source :
-
PloS one [PLoS One] 2013 Jun 04; Vol. 8 (6), pp. e63656. Date of Electronic Publication: 2013 Jun 04 (Print Publication: 2013). - Publication Year :
- 2013
-
Abstract
- Oxidative stress is considered to be a major factor contributing to pathogenesis and progression of many diseases. A novel andrographolide-lipoic acid conjugate (AL-1) could protect pancreatic β-cells from reactive oxygen species (ROS)-induced oxidative injury. However, its protective mechanism is still unclear. In this work, we used proteomics to identify AL-1-regulated proteins in β-cells and found that 13 of the 71 proteins regulated by AL-1 were closely associated with antioxidation. These differential proteins were mainly involved in the ERK1/2 and AKT1 signaling pathways. Functional investigation demonstrated that AL-1 exerted its protective effects on H2O2-induced cell death of β-cells by generating NADPH oxidase-dependent ROS to activate ERK1/2 and AKT1 signaling pathways. As a consequence, the expressions of antioxidant proteins including Trx1, Prx1 and Prx5, and anti-apoptotic proteins including PDCD6IP, prohibitin, galectin-1 and HSP were upregulated. AL-1 probably worked as a "vaccinum" to activate the cellular antioxidant system by inducing the generation of low concentration ROS which then reciprocally protected β-cells from oxidative damage caused by high-level ROS from H2O2. To the best of our knowledge, this is the first comprehensive proteomic analysis illustrating a novel molecular mechanism for the protective effects of antioxidants on β-cells from H2O2-induced cell death.
- Subjects :
- Animals
Antioxidants metabolism
Cell Death drug effects
Cell Line, Tumor
Hydrogen Peroxide pharmacology
Insulin-Secreting Cells drug effects
Insulin-Secreting Cells metabolism
NADPH Oxidases metabolism
Oxidative Stress drug effects
Protein Interaction Maps drug effects
Proteomics
Rats
Up-Regulation drug effects
Cytoprotection drug effects
Diterpenes chemistry
Diterpenes pharmacology
Insulin-Secreting Cells cytology
Reactive Oxygen Species metabolism
Thioctic Acid chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23750203
- Full Text :
- https://doi.org/10.1371/journal.pone.0063656