Insulin-like growth factor II receptor-α is a novel stress-inducible contributor to cardiac damage underpinning doxorubicin-induced oxidative stress and perturbed mitochondrial autophagy.
Doxorubicin (DOX) is an anthracycline antibiotic commonly used to treat various types of cancer. However, the therapeutic use is hampered by side effects associated with cumulative dose during treatment. While deregulation of autophagy in the myocardium have been involved in a variety of cardiovascular diseases, the role of autophagy in the remnants of DOX-induced cardiomyopathy debated. Our studies have previously shown that treatment of DOX in a rat animal model that leads to increased expression of novel stress-induced protein insulin-like growth factor II receptor-α (IGF-IIRα) in heart tissue, which worsens cardiac injury by increasing oxidative stress and p53 -mediated mitochondrial dependent apoptosis of heart.
Through this study, we investigate the contribution of IGF-IIRα to dysregulation of autophagy in the liver using both in cell H9c2 vitro (DOX treated, 1 M) and in vivo transgenic mouse model (DOX-treated, 5 mg / kg ip for 6 weeks) overexpressing IGF Special -IIRα in the heart. We found that IGF-IIRα mainly translated into mitochondria, causing an increase in severe mitochondrial oxidative stress exacerbated by DOX treatment.
It is accompanied by a significant disturbance in the mitochondrial membrane potential and increased leakage of cytochrome c, resulting in an increase in cleaved caspase-3 activity. There is a significant change in the phosphorylated AMP-activated protein kinase (p-AMPK), phosphorylated Unc-51 like kinase-1 (p-ULK1), Parkin, PTEN-induced kinase 1 (PINK1), microtubule-associated protein 1 light chain 3 ( LC3), and the P62 protein, which is more severe impaired under the combined effects of IGF-IIRα excess plus DOX.
Finally, LysoTracker Red staining showed that IGF-IIRα excess causes damage to the lysosomes, which was saved by Rapamycin treatment. Taken together, we found that IGF-IIRα leading to mitochondrial oxidative stress, decreased antioxidant levels, impaired mitochondrial membrane potential, and impaired mitochondrial autophagy contributes to DOX-induced cardiomyopathy.
Insulin-like growth factor II receptor-α is a novel stress-inducible contributor to cardiac damage underpinning doxorubicin-induced oxidative stress and perturbed mitochondrial autophagy.
Insulin – like growth factor two regulate the proliferation and differentiation of stromal cells of mice adipose- came through the IGF-1R and IR.
Insulin-like growth factor 2 (IGF2), an essential component of the stem cell niche, has been reported to modulate the proliferation and differentiation of stem cells. Previously, the expression of IGF2 in the network continuously reported for maintaining self-renewal ability of some types of stem cells. Therefore, in this study, we investigated the IGF2 expression in adipose tissue and explore the IGF2 effect on adipose-derived stromal cells (ADSCs) in vitro.
The pattern IGF2 expression in rat adipose tissue is determined by gene expression and protein analysis. IGF2 influence on proliferation, associated stemness marker expression and adipogenic and osteogenic differentiation systematically investigated. Furthermore, antagonists of IGF2 receptor-specific-that is, BMS-754 807 and picropodophyllin-written to explore the underlying signal transduction mechanisms.IGF2 levels displayed a tendency to decrease with age in rat adipose tissue.
After the addition of IGF2, isolated ADSCs displayed a higher proliferation and expression of markers associated stemness NANOG, OCT4 and Sox2 and the potential for greater differentiation to adipocytes and osteoblasts. In addition, both type 1 insulin-like growth factor receptor (IGF-1R) and insulin receptor (IR) participate in the promotion of IGF2-mediated stemness in ADSCs.
Description: The protein encoded by this gene is similar to insulin in function and structure and is a member of a family of proteins involved in mediating growth and development. The encoded protein is processed from a precursor, bound by a specific receptor, and secreted. Defects in this gene are a cause of insulin-like growth factor I deficiency. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar processing to generate mature protein.
Description: The protein encoded by this gene is similar to insulin in function and structure and is a member of a family of proteins involved in mediating growth and development. The encoded protein is processed from a precursor, bound by a specific receptor, and secreted. Defects in this gene are a cause of insulin-like growth factor I deficiency. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar processing to generate mature protein.
Description: The protein encoded by this gene is similar to insulin in function and structure and is a member of a family of proteins involved in mediating growth and development. The encoded protein is processed from a precursor, bound by a specific receptor, and secreted. Defects in this gene are a cause of insulin-like growth factor I deficiency. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar processing to generate mature protein.
Description: A Monoclonal antibody against Human IGF1R / IGF1 Receptor. The antibodies are raised in Mouse. This antibody is applicable in WB and IHC-P, E, Flo
Description: A sandwich quantitative ELISA assay kit for detection of Bovine Insulin Like Growth Factor 1 (IGF1) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Bovine Insulin Like Growth Factor 1 (IGF1) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Bovine Insulin Like Growth Factor 1 (IGF1) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Canine Insulin Like Growth Factor 1 (IGF1) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Canine Insulin Like Growth Factor 1 (IGF1) in samples from serum, plasma or other biological fluids.
Canine Insulin Like Growth Factor 1 (IGF1) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Canine Insulin Like Growth Factor 1 (IGF1) in samples from serum, plasma or other biological fluids.
Chicken Insulin Like Growth Factor 1 (IGF1) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Chicken Insulin Like Growth Factor 1 (IGF1) in samples from serum, plasma or other biological fluids.
Chicken Insulin Like Growth Factor 1 (IGF1) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Chicken Insulin Like Growth Factor 1 (IGF1) in samples from serum, plasma or other biological fluids.
Human Insulin Like Growth Factor 1 (IGF1) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Human Insulin Like Growth Factor 1 (IGF1) in samples from serum, plasma or other biological fluids.
Human Insulin Like Growth Factor 1 (IGF1) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Human Insulin Like Growth Factor 1 (IGF1) in samples from serum, plasma or other biological fluids.
Mouse Insulin Like Growth Factor 1 (IGF1) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Mouse Insulin Like Growth Factor 1 (IGF1) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Mouse Insulin Like Growth Factor 1 (IGF1) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Mouse Insulin Like Growth Factor 1 (IGF1) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Porcine Insulin Like Growth Factor 1 (IGF1) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Porcine Insulin Like Growth Factor 1 (IGF1) in samples from serum, plasma or other biological fluids.
Porcine Insulin Like Growth Factor 1 (IGF1) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Porcine Insulin Like Growth Factor 1 (IGF1) in samples from serum, plasma or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Rat Insulin Like Growth Factor 1 (IGF1) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Rat Insulin Like Growth Factor 1 (IGF1) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Rabbit Insulin Like Growth Factor 1 (IGF1) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Rabbit Insulin Like Growth Factor 1 (IGF1) in samples from serum, plasma or other biological fluids.
Rabbit Insulin Like Growth Factor 1 (IGF1) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Rabbit Insulin Like Growth Factor 1 (IGF1) in samples from serum, plasma or other biological fluids.
Sheep Insulin Like Growth Factor 1 (IGF1) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Sheep Insulin Like Growth Factor 1 (IGF1) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Sheep Insulin Like Growth Factor 1 (IGF1) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Sheep Insulin Like Growth Factor 1 (IGF1) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Bovine Insulin Like Growth Factor 1 (IGF1) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Guinea pig Insulin Like Growth Factor 1 (IGF1) in samples from serum, plasma or other biological fluids.
Guinea pig Insulin Like Growth Factor 1 (IGF1) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Guinea pig Insulin Like Growth Factor 1 (IGF1) in samples from serum, plasma or other biological fluids.
Guinea pig Insulin Like Growth Factor 1 (IGF1) ELISA Kit
Description: A polyclonal antibody against IGF1. Recognizes IGF1 from Human. This antibody is Unconjugated. Tested in the following application: ELISA, IHC;ELISA:1:2000-1:5000, IHC:1:25-1:100
Description: A polyclonal antibody against IGF1. Recognizes IGF1 from Human. This antibody is Unconjugated. Tested in the following application: ELISA, IHC; Recommended dilution: IHC:1:200-1:500
Description: A polyclonal antibody against IGF1. Recognizes IGF1 from Human, Mouse, Rat. This antibody is Unconjugated. Tested in the following application: IHC, ELISA;IHC:1/100-1/300.ELISA:1/10000
Description: A polyclonal antibody against IGF1. Recognizes IGF1 from Human, Mouse, Rat. This antibody is Unconjugated. Tested in the following application: ELISA, WB, IHC;WB:1:500-1:2000, IHC:1:50-1:200
Description: A polyclonal antibody against IGF1. Recognizes IGF1 from Human, Mouse, Rat. This antibody is Unconjugated. Tested in the following application: ELISA, WB, IHC;WB:1:500-1:2000, IHC:1:50-1:200
Description: A polyclonal antibody raised in Rabbit that recognizes and binds to Human IGF1 Receptor (IGF1R) (N-term). This antibody is tested and proven to work in the following applications:
Description: A polyclonal antibody raised in Rabbit that recognizes and binds to Human IGF1 Receptor (IGF1R) (C-term). This antibody is tested and proven to work in the following applications:
Description: A polyclonal antibody raised in Rabbit that recognizes and binds to Human IGF1R / IGF1 Receptor (aa1126-1175). This antibody is tested and proven to work in the following applications:
Description: A Monoclonal antibody against Human IGF1R / IGF1 Receptor (clone 1H7). The antibodies are raised in Mouse and are from clone 1H7. This antibody is applicable in WB and IHC-P, Flo
Description: A polyclonal antibody against IGF1. Recognizes IGF1 from Human. This antibody is HRP conjugated. Tested in the following application: ELISA
Description: A polyclonal antibody against IGF1. Recognizes IGF1 from Human. This antibody is FITC conjugated. Tested in the following application: ELISA
Description: A polyclonal antibody against IGF1. Recognizes IGF1 from Human. This antibody is Biotin conjugated. Tested in the following application: ELISA
Description: Primary antibody against IGF-1(IGF1/1020), Biotin conjugate, Concentration: 0.1mg/mL
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Our findings show that IGF2 can improve stemness of rat ADSCs through IGF-1R and IR and can highlight an effective method for the expansion of ADSCs for clinical applications.