RGD Reference Report - Thapsigargin down-regulates protein levels of GRP78/BiP in INS-1E cells. - Rat Genome Database

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Thapsigargin down-regulates protein levels of GRP78/BiP in INS-1E cells.

Authors: Rosengren, V  Johansson, H  Lehtio, J  Fransson, L  Sjoholm, A  Ortsater, H 
Citation: Rosengren V, etal., J Cell Biochem. 2012 May;113(5):1635-44. doi: 10.1002/jcb.24032.
RGD ID: 11354954
Pubmed: PMID:22189689   (View Abstract at PubMed)
DOI: DOI:10.1002/jcb.24032   (Journal Full-text)

Pancreatic beta-cells have a well-developed endoplasmic reticulum (ER) and express large amounts of chaperones and protein disulfide isomerases (PDI) to meet the high demand for synthesis of proteins. We have observed an unexpected decrease in chaperone protein level in the beta-cell model INS-1E after exposure to the ER stress inducing agent thapsigargin. As these cells are a commonly used model for primary beta-cells and has been shown to be vulnerable to ER stress, we hypothesize these cells are incapable of mounting a chaperone defense upon activation of ER stress. To investigate the chaperone expression during an ER stress response, induced by thapsigargin in INS-1E cells, we used quantitative mass spectrometry based proteomics. The results displayed a decrease of GRP78/BiP, PDIA3 and PDIA6. Decrease of GRP78/BiP was verified by Western blot and occurred in parallel with enhanced levels of p-eIF2alpha and CHOP. In contrast to INS-1E cells, GRP78/BiP was not decreased in MIN6 cell or rat and mouse islets after thapsigargin exposure. Investigation of the decreased protein levels of GRP78/BiP indicates that this is not a consequence of reduced mRNA expression. Rather the reduction results from the combined effect of reduced protein synthesis and enhanced proteosomal degradation and possibly also degradation via autophagy. Induction of ER stress with thapsigargin leads to lower protein levels of GRP78/BiP, PDIA3 and PDIA6 in INS-1E cells which may contribute to the susceptibility of ER stress in this beta-cell model.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Hspa5Ratresponse to endoplasmic reticulum stress  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hspa5  (heat shock protein family A (Hsp70) member 5)


Additional Information