Translationally controlled tumour protein (TCTP) is a novel glucose-regulated protein that is important for survival of pancreatic beta cells

Autor: Elek Molnár, Flora Brozzi, Neil D. Avent, Sophie Lajus, Kelly Sanders, E Ainscow, Ulrich-Axel Bommer, J Hancock, Aniko Varadi, K Hayward, JE Francis, Frédérique Diraison
Rok vydání: 2010
Předmět:
Small interfering RNA
Programmed cell death
Glucose-regulated protein
Cell Survival
Endocrinology
Diabetes and Metabolism
Apoptosis
Palmitic Acids
Cell Line
03 medical and health sciences
Mice
0302 clinical medicine
Insulin-Secreting Cells
Internal Medicine
Biomarkers
Tumor
In Situ Nick-End Labeling
Animals
Humans
Electrophoresis
Gel
Two-Dimensional
HSP70 Heat-Shock Proteins
RNA
Small Interfering
030304 developmental biology
0303 health sciences
Gene knockdown
biology
Reverse Transcriptase Polymerase Chain Reaction
Membrane Proteins
Tumor Protein
Translationally-Controlled 1
Cell biology
Biochemistry
Cell culture
030220 oncology & carcinogenesis
Spectrometry
Mass
Matrix-Assisted Laser Desorption-Ionization
biology.protein
Translationally controlled tumour protein
Beta cell
Isoelectric Focusing
Zdroj: Diabetologia. 54(2)
ISSN: 1432-0428
Popis: This study used proteomics and biochemical approaches to identify novel glucose-regulated proteins and to unveil their role in pancreatic beta cell function. Translationally controlled tumour protein (TCTP) was identified to be one such protein, and further investigations into its function and regulation were carried out. Global protein profiling of beta cell homogenates following glucose stimulation was performed using two-dimensional gel electrophoresis. Proteins were identified by mass spectroscopy analysis. Immunoblotting was used to investigate alterations in TCTP protein levels in response to glucose stimulation or cell stress induced by palmitate. To investigate the biological function of TCTP, immunolocalisation, gene knockdown and overexpression of Tctp (also known as Tpt1) were performed. Apoptosis was measured in Tctp knockdown or Tctp-overexpressing cells. Glucose-stimulated insulin secretion was carried out in Tctp knockdown cells. TCTP was identified as a novel glucose-regulated protein, the level of which is increased at stimulatory glucose concentration. Glucose also induced TCTP dephosphorylation and its partial translocation to the mitochondria and the nucleus. TCTP protein levels were downregulated in response to cell stress induced by palmitate or thapsigargin treatments. Gene knockdown by small interfering RNA led to increased apoptosis, whereas overproduction of TCTP prevented palmitate-induced cell death. Regulation of TCTP protein levels by glucose is likely to be an important cyto-protective mechanism for pancreatic beta cells against damage caused by hyperglycaemia. In contrast, high concentration of palmitate causes cell stress, reduction in TCTP levels and consequently reduced cell viability. Our results imply that TCTP levels influence the sensitivity of beta cells to apoptosis.
Databáze: OpenAIRE
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