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

Concept-gene networks of enriched biological processes of AL-1-regulated proteins that were analyzed by Bioconductor package clusterProfiler and visualized by GeneAnswers program.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3672203&req=5

pone-0063656-g004: Concept-gene networks of enriched biological processes of AL-1-regulated proteins that were analyzed by Bioconductor package clusterProfiler and visualized by GeneAnswers program.

Mentions: Interestingly, among the 71 AL-1-regulated differences, 13 proteins including thioredoxin 1 (Trx 1), peroxiredoxin 1 (Prx 1), peroxiredoxin 5 (Prx 5), glutamate-cysteine ligase, 14-3-3ξ, RHO-GDI1, DJ-1, and heat shock protein (HSP) family such as Hspa8, Hspa14, Hyou1, Hsph1 and Hsp90ab1 were known to be associated with anti-oxidation (Table 1). The enrichment of the antioxidant proteins suggested that AL-1 exerted its protective effect against H2O2-induced cell death possibly by regulating anti-oxidant proteins. Gene Ontology (GO) annotation and Ingenuity Pathway Analysis (IPA) were used to further analyze these AL-1-regulated proteins in terms of the biological process (BP) and involved signaling pathways. GO annotation showed that these differential proteins were mainly categorized into four significant groups according to their biological processes, including oxidation-reduction process, NADPH regeneration, glucose catabolic process and cell death by Bioconductor package clusterProfiler and GeneAnswers program (Fig. 4) [20], [21]. IPA analysis demonstrated that the 71 proteins were involved in five canonical pathways, including NRF2-mediated oxidative stress response, glycolysis, pentose phosphate pathway, pentose phosphate pathway (non-oxidative branch), sucrose degradation (mammalian), belonging to the two groups of oxidative stress response and carbohydrate metabolism. As shown in Figure 4, there is a crosstalk between the two signaling pathways of oxidative stress response and carbohydrate metabolism. We therefore speculate that AL-1 exerts its protective effect against H2O2-induced cell death by inducing oxidative stress response and upregulating anti-oxidant proteins.


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)

Concept-gene networks of enriched biological processes of AL-1-regulated proteins that were analyzed by Bioconductor package clusterProfiler and visualized by GeneAnswers program.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0063656-g004: Concept-gene networks of enriched biological processes of AL-1-regulated proteins that were analyzed by Bioconductor package clusterProfiler and visualized by GeneAnswers program.
Mentions: Interestingly, among the 71 AL-1-regulated differences, 13 proteins including thioredoxin 1 (Trx 1), peroxiredoxin 1 (Prx 1), peroxiredoxin 5 (Prx 5), glutamate-cysteine ligase, 14-3-3ξ, RHO-GDI1, DJ-1, and heat shock protein (HSP) family such as Hspa8, Hspa14, Hyou1, Hsph1 and Hsp90ab1 were known to be associated with anti-oxidation (Table 1). The enrichment of the antioxidant proteins suggested that AL-1 exerted its protective effect against H2O2-induced cell death possibly by regulating anti-oxidant proteins. Gene Ontology (GO) annotation and Ingenuity Pathway Analysis (IPA) were used to further analyze these AL-1-regulated proteins in terms of the biological process (BP) and involved signaling pathways. GO annotation showed that these differential proteins were mainly categorized into four significant groups according to their biological processes, including oxidation-reduction process, NADPH regeneration, glucose catabolic process and cell death by Bioconductor package clusterProfiler and GeneAnswers program (Fig. 4) [20], [21]. IPA analysis demonstrated that the 71 proteins were involved in five canonical pathways, including NRF2-mediated oxidative stress response, glycolysis, pentose phosphate pathway, pentose phosphate pathway (non-oxidative branch), sucrose degradation (mammalian), belonging to the two groups of oxidative stress response and carbohydrate metabolism. As shown in Figure 4, there is a crosstalk between the two signaling pathways of oxidative stress response and carbohydrate metabolism. We therefore speculate that AL-1 exerts its protective effect against H2O2-induced cell death by inducing oxidative stress response and upregulating anti-oxidant proteins.

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