Limits...
Protective effects of andrographolide analogue AL-1 on ROS-induced RIN-mβ cell death by inducing ROS generation.

Yan GR, Zhou HH, Wang Y, Zhong Y, Tan ZL, Wang Y, He QY - PLoS ONE (2013)

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, China. tgryan@jnu.edu.cn

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.

Show MeSH

Related in: MedlinePlus

Molecular mode of the protective effects of AL-1 on H2O2-induced pancreatic β-cell death.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3672203&req=5

pone-0063656-g007: Molecular mode of the protective effects of AL-1 on H2O2-induced pancreatic β-cell death.

Mentions: Taken together, these results suggest that AL-1 exerted its protective effects on H2O2-induced apoptosis by generating low dose of ROS to activate ERK1/2 and AKT1 signaling pathways and subsequently upregulated antioxidant proteins such as Trx1 and Prx5 (Fig. 7).


Protective effects of andrographolide analogue AL-1 on ROS-induced RIN-mβ cell death by inducing ROS generation.

Yan GR, Zhou HH, Wang Y, Zhong Y, Tan ZL, Wang Y, He QY - PLoS ONE (2013)

Molecular mode of the protective effects of AL-1 on H2O2-induced pancreatic β-cell death.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3672203&req=5

pone-0063656-g007: Molecular mode of the protective effects of AL-1 on H2O2-induced pancreatic β-cell death.
Mentions: Taken together, these results suggest that AL-1 exerted its protective effects on H2O2-induced apoptosis by generating low dose of ROS to activate ERK1/2 and AKT1 signaling pathways and subsequently upregulated antioxidant proteins such as Trx1 and Prx5 (Fig. 7).

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, China. tgryan@jnu.edu.cn

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.

Show MeSH
Related in: MedlinePlus