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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2015.tde-07122015-203814
Document
Author
Full name
Douglas Amaral dos Santos
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2015
Supervisor
Committee
Santos, Marinilce Fagundes dos (President)
Santelli, Glaucia Maria Machado
Silva, Silvana Auxiliadora Bordin da
Vanzela, Emerielle Cristine
Title in Portuguese
Efeitos da elevada concentração de glicose sobre o retículo endoplasmático em fibroblastos.
Keywords in Portuguese
Diabetes Mellitus
Estresse do RE
Fibroblasto
Hiperglicemia
Abstract in Portuguese
Fibroblastos são células essenciais na cicatrização da derme, sintetizando e degradando matriz extracelular (MEC) e sua função é alterada pela hiperglicemia. Demonstramos previamente uma deficiência na migração de fibroblastos de ratos diabéticos, acompanhada de dilatação das cisternas do retículo endoplasmático (RE) e aumento no número de mitocôndrias. Neste estudo avaliamos se a glicose elevada (HG) induz estresse do RE, resultando na ativação da via UPR (Unfolded Protein Response). Conforme observado por microscopia eletrônica de transmissão, fibroblastos NIH-3T3 expostos por 3 dias a HG apresentaram dilatação do RE e alteração na morfologia das mitocôndrias. A expressão dos marcadores de estresse do RE: BiP, XBP1 spliced (XBP1s) e CHOP não foi alterada pela HG. Resultados semelhantes foram observados em fibroblastos de ratos diabéticos. A marcação com um indicador fluorescente do potencial de membrana mitocondrial não foi modificada pela glicose elevada. Esses resultados sugerem que a disfunção de fibroblastos frente à HG não está relacionada a estresse de RE.
Title in English
Effects of high glucose concentration on the endoplasmic reticulum of fibroblasts.
Keywords in English
Diabetes Mellitus
ER stress
Fibroblast
Hyperglycemia
Abstract in English
Fibroblasts are essential cells during dermis wound healing, synthesizing and degrading extracellular matrix (ECM); their function is altered by hyperglycemia. We have previously demonstrated an impairment of migration of fibroblasts derived from diabetic rats, accompanied by the enlargement of endoplasmic reticulum (ER) cisternae and an increase in the number of mitochondria. This study assessed whether high glucose (HG) induces stress of ER, resulting in the activation of UPR (Unfolded Protein Response). As observed by transmission electron microscopy, NIH-3T3 fibroblasts exposed for 3 days to HG showed enlargement of the ER cisternae and changes in the morphology of mitochondria. The expression of the ER stress markers: BiP, spliced XBP1 (XBP1s) and CHOP was not altered by HG. Similar results were observed in fibroblasts derived from diabetic rats. Labeling with a fluorescent indicator of mitochondrial membrane potential was not altered by high glucose. These results suggest that dysfunction of fibroblasts exposed to HG is not related to ER stress.
 
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Publishing Date
2015-12-08
 
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