DIACEREIN TREATMENT DOES NOT RESTORE ENDOPLASMIC RETICULUM FUNCTION UNDER PALMITATE INDUCED INFLAMMATION AND ENDOPLASMIC RETICULUM STRESS IN INS1-E BETA CELLS
NELO EIDY ZANCHI *
Department of Physiology and Biophysics, University of São Paulo, Brazil
GABRIELA VIRGÍNIA MOREIRA
Department of Physiology and Biophysics, University of São Paulo, Brazil
JASON CHOLEWA
Department of Kinesiology Recreation and Sport Studies, Coastal Carolina University, Conway, SC, USA
LUCAS GUIMARÃES- FERREIRA
Laboratory of Experimental Physiology and Biochemistry, Federal University of Espirito Santo, Vitoria, ES, Brazil
KATHERINE VERAS
Department of Physiology and Biophysics, University of São Paulo, Brazil
FELIPE NATALI ALMEIDA
Department of Physiology and Biophysics, University of São Paulo, Brazil
TAINÁ WEBBER
Department of Physiology and Biophysics, University of São Paulo, Brazil
DANIELA SEIXAS
Laboratory of Applied Nutrition and Metabolism, Physical Education and School of Sports, University of São Paulo, São Paulo, Brazil
ANTONIO HERBERT LANCHA-JR
Laboratory of Applied Nutrition and Metabolism, Physical Education and School of Sports, University of São Paulo, São Paulo, Brazil
CARLA ROBERTA DE OLIVEIRA CARVALHO
Department of Physiology and Biophysics, University of São Paulo, Brazil
*Author to whom correspondence should be addressed.
Abstract
The non-steroidal anti-inflammatory drug Diacerein has been shown to reduce markers of inflammation in animal models of type 2 diabetes mellitus; however, the effects of Diacerein on endoplasmic reticulum stress mediated inflammation are unknown. The aim of the current study was to investigate the potential protective role of Diacerein against palmitate-induced induction of ER stress and markers of apoptosis in pancreatic INS-1E beta cells. Three plates of INS-1E cells were treated with palmitate, palmitate and Diacerein, or maintained as control. Palmitate resulted in the induction of the protein tubulin alpha 1 and eukaryotic elongation factor Eef1 and inhibited the protein expression of mitochondrial malic enzyme and protein isoform 1 of ribonucleus protein (HNRPD). Palmitate was shown to decrease expression of eukaryotic initiation factor eIF2 (Control 100% vs Palmitate 51%; P = .05), responsible for global translation of mRNA; however there were no differences between conditions. Western blot analysis demonstrated that Diacerein did not restore key proteins in apoptotic pathway including CHOP/GADD 34 and CHOP/GADD 153. Thus, our experiments suggest that while palmitate treatment reduced global protein synthesis inducing ER stress, Diacerein treatment does not appear to play a protective role in INS1-E under conditions of ER stress induced cellular damage.
Keywords: Diacerein, Palmitate, apoptosis, endoplasmatic reticulum (ER) stress, diabetes