Premium
Sodium 4‐phenylbutyrate reverses glucose deprivation‐induced endoplasmic reticulum stress and death signal in cultured mouse microvascular endothelial cells (1051.3)
Author(s) -
Samuel Samson,
Arunachalam Gnanapragasam,
Ghosh Suparna,
Emara Mohamed,
Ding Hong,
Triggle Chris
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1051.3
Subject(s) - endoplasmic reticulum , unfolded protein response , endocrinology , medicine , autophagy , chemical chaperone , apoptosis , endothelial stem cell , intracellular , chop , programmed cell death , stress hyperglycemia , diabetes mellitus , chemistry , biology , microbiology and biotechnology , biochemistry , in vitro
In diabetes mellitus, despite higher than normal levels of blood glucose, deficiencies in signaling mechanisms results in a failure to utilize glucose, creating a scenario of variable glucose deprivation (GD). Reports suggest that stringent control of blood glucose in diabetic subjects invariably increases the risk of hypoglycemia, the severity of which is associated with increased cardiovascular risk. However, in such conditions the possible role of endoplasmic reticulum (ER) stress associated cell death during GD in microvascular endothelial cells has not been studied. Mouse Microvascular Endothelial cells (MMECs) subjected to GD for 24h showed significant increase in the levels of GRP78, p‐eIF2α, ATF4 & pro‐apoptotic CHOP, while levels of total PERK decreased & total‐ eIF2α did not change. Autophagic markers showed significant up‐regulation upon GD. 10mM of 4PBA, a chemical chaperone, significantly reversed the GD induced changes in ER stress & autophagic markers. Immunocytochemical analysis revealed that stress granules (SGs) are assembled at early hours (1h‐8h) of GD while very few SGs are observed at 16h‐24h. Our data suggests that GD induced ER stress & associated activation of death signal could play a major role in GD associated endothelial cell loss, which could be reversed by treatment with suitable chaperones. Grant Funding Source : Supported by: QNRF grants # NPRP 4‐910‐3‐244 & JSREP 3‐016‐3‐009