With resveratrol (100 uM) for 24 h. (XLS) S3 Table. Methylation raw data for MDA-MB-231 cells treated with resveratrol (100 uM) for 48 h. (XLS) S4 Table. Tumor suppressor genes that change from hypermethylated to hypomethylated status in MDA-MB-231 breast cancer cells treated with resveratrol (100 M) at 24 h. (DOC) S5 Table. Tumor suppressor genes that change from hypermethylated to hypomethylated status in MDA-MB-231 breast cancer cells treated with resveratrol (100 M) at 48 h. (DOC) S6 Table. Oncogenes that change from hypomethylated to hypermethylated status in MDA-MB-231 breast cancer cells treated with resveratrol (100 M) at 24 h. (DOC) S7 Table. Oncogenes that change from hypomethylated to hypermethylated status in MDA-MB-231 breast cancer cells treated with resveratrol (100 M) at 48 h. (DOC)PLOS ONE | DOI:10.1371/journal.pone.0157866 June 29,17 /Methylation Landscape of Breast Cancer Cells in Response to ResveratrolAcknowledgmentsWe thanks to Universidad Aut oma de la Ciudad de M ico (UACM) for support. Rubiceli Medina was supported by CONACYT fellowship.Author ContributionsConceived and designed the experiments: RMA CPP LAM PG JGM CLC. Performed the experiments: RMA CLC AFP CPP JHJ. Analyzed the data: RMA LAM AFP SRC CLC. Contributed reagents/materials/analysis tools: RMA LAM CPP SRC CLC. Wrote the paper: RMA CPP LAM PG JGM SRC ERG HAV JHJ AFP CLC.
As the primary tissue responsible for post-prandial glucose disposal [1], skeletal muscle plays a key role in regulating metabolism. Skeletal muscle insulin resistance is an early event in the development of Type 2 Diabetes (T2D) [2]. Aside from its roles in locomotion and metabolism, skeletal muscle has been shown to act as an endocrine tissue, with the capacity to synthesize and secrete multiple factors, now referred to as `myokines’ [3]. A major advance in this area was the observation of Pedersen and colleagues that increases in circulating IL6 following exercise resulted from increases in skeletal muscle IL-6 synthesis and secretion [4]. Since those early findings an increasing number of other myokines have been identified [5]. AlthoughPLOS ONE | DOI:10.1371/journal.pone.0158209 July 25,1 /Myokine Secretion in Type 2 Diabetesmany of these factors, including cytokines and chemokines are produced by multiple cell types [6], some appear to be more exclusive to muscle, such as myostatin [7]. Focusing on studies in human muscle, the synthesis and secretion of myokines is regulated by a number of conditions including; differentiation [8], exercise [5], electrical stimulation in vitro [9, 10] and induction of insulin resistance [11]. Studies of the impact of T2D on myokine production are limited. Cultured U0126-EtOH site myotubes from T2D subjects displayed elevated mRNA content for TNFa and MCP-1 compared to cells from non-diabetic (ND) individuals [12]; we reported previously that release of TNFa protein was also elevated [13]. Meanwhile, IL6 mRNA and secretion did not P144 Peptide web differ between T2D and ND myotubes [12, 14]. However, caution must be exerted while determining the significance of changes in mRNA content, as there are multiple examples of discrepancies between mRNA content and expression and/or secretion of the same protein [15]. Studies performed in primary or cultured myotubes can provide specific information about the regulation of myokine synthesis and secretion. Human skeletal muscle satellite cells cultured and differentiated to myotubes (hSMC) have been validated as a system that retains many.With resveratrol (100 uM) for 24 h. (XLS) S3 Table. Methylation raw data for MDA-MB-231 cells treated with resveratrol (100 uM) for 48 h. (XLS) S4 Table. Tumor suppressor genes that change from hypermethylated to hypomethylated status in MDA-MB-231 breast cancer cells treated with resveratrol (100 M) at 24 h. (DOC) S5 Table. Tumor suppressor genes that change from hypermethylated to hypomethylated status in MDA-MB-231 breast cancer cells treated with resveratrol (100 M) at 48 h. (DOC) S6 Table. Oncogenes that change from hypomethylated to hypermethylated status in MDA-MB-231 breast cancer cells treated with resveratrol (100 M) at 24 h. (DOC) S7 Table. Oncogenes that change from hypomethylated to hypermethylated status in MDA-MB-231 breast cancer cells treated with resveratrol (100 M) at 48 h. (DOC)PLOS ONE | DOI:10.1371/journal.pone.0157866 June 29,17 /Methylation Landscape of Breast Cancer Cells in Response to ResveratrolAcknowledgmentsWe thanks to Universidad Aut oma de la Ciudad de M ico (UACM) for support. Rubiceli Medina was supported by CONACYT fellowship.Author ContributionsConceived and designed the experiments: RMA CPP LAM PG JGM CLC. Performed the experiments: RMA CLC AFP CPP JHJ. Analyzed the data: RMA LAM AFP SRC CLC. Contributed reagents/materials/analysis tools: RMA LAM CPP SRC CLC. Wrote the paper: RMA CPP LAM PG JGM SRC ERG HAV JHJ AFP CLC.
As the primary tissue responsible for post-prandial glucose disposal [1], skeletal muscle plays a key role in regulating metabolism. Skeletal muscle insulin resistance is an early event in the development of Type 2 Diabetes (T2D) [2]. Aside from its roles in locomotion and metabolism, skeletal muscle has been shown to act as an endocrine tissue, with the capacity to synthesize and secrete multiple factors, now referred to as `myokines’ [3]. A major advance in this area was the observation of Pedersen and colleagues that increases in circulating IL6 following exercise resulted from increases in skeletal muscle IL-6 synthesis and secretion [4]. Since those early findings an increasing number of other myokines have been identified [5]. AlthoughPLOS ONE | DOI:10.1371/journal.pone.0158209 July 25,1 /Myokine Secretion in Type 2 Diabetesmany of these factors, including cytokines and chemokines are produced by multiple cell types [6], some appear to be more exclusive to muscle, such as myostatin [7]. Focusing on studies in human muscle, the synthesis and secretion of myokines is regulated by a number of conditions including; differentiation [8], exercise [5], electrical stimulation in vitro [9, 10] and induction of insulin resistance [11]. Studies of the impact of T2D on myokine production are limited. Cultured myotubes from T2D subjects displayed elevated mRNA content for TNFa and MCP-1 compared to cells from non-diabetic (ND) individuals [12]; we reported previously that release of TNFa protein was also elevated [13]. Meanwhile, IL6 mRNA and secretion did not differ between T2D and ND myotubes [12, 14]. However, caution must be exerted while determining the significance of changes in mRNA content, as there are multiple examples of discrepancies between mRNA content and expression and/or secretion of the same protein [15]. Studies performed in primary or cultured myotubes can provide specific information about the regulation of myokine synthesis and secretion. Human skeletal muscle satellite cells cultured and differentiated to myotubes (hSMC) have been validated as a system that retains many.
