Attenuation of unfolded protein response and apoptosis by mReg2 induced GRP78 in mouse insulinoma cells

AbstractMurine regenerating (mReg) genes have been implicated in preserving islet cell biology. Expanding on our previous work showing that overexpression of mReg2 protects MIN6 insulinoma cells against streptozotocin-induced apoptosis, we now demonstrate that mReg2 induces glucose-regulated peptide 78 (GRP78) expression via the Akt–mTORC1 axis and protects MIN6 cells against ER stress induced by thapsigargin and glucolipotoxicity. Activation of mTORC1 activity results from both mReg2-induced increased mTOR phosphorylation as well as increased expression of Raptor and GβL. Inhibition of Akt and mTORC1 blunted the ability of mReg2 to induce GRP78 and attenuate unfolded protein response (UPR). Knockdown of GRP78 sensitized the cells overexpressing mReg2 to UPR without affecting its ability to activate Akt–mTORC1 signaling. Induced expression of mReg2 may protect insulin producing cells from ER stress in diabetes

A human somatostatin receptor (SSTR3), located on chromosome 22, displays preferential affinity for somatostatin-14 like peptides

AbstractWe report here on the cloning of a human intronless gene encoding a member of the G-protein linked somatostatin (SST) receptor subfamily, termed SSTR3. Based on the deduced amino acid sequence, this gene encodes a 418 amino acid protein displaying sequence similarity, particularly within putative transmembrane domains, with the recently cloned human SSTR1 (62%), SSTR2 (64%) and SSTR4 (58%) receptors. Membranes prepared from COS-7 cells transiently expressing the human SSTR3 gene bound [125I]Leu8,d-Trp22,-Tyr22 SST-28 in a saturable manner with high affinity (~200 pM) and with rank order of potency (d-Trp8 SST-14 > SST-14 > SMS-201-995 > SST-28) indicative of a somatostatin-14 selective receptor. The pharmacological profile of the expressed human SSTR3 receptor is similar but not identical to that reported for the rat homolog [(1992) J. Biol. Chem. 267,20422] where the peptide selectivity is SST-28 ≧ SST-14 XXX SMS-201-995. Northern blot analysis reveals the presence of an SSTR3 mRNA species of ~5 kb in various regions of the monkey brain, including the frontal cortex, cerebellum, medulla, amygdala, with little or no SSTR3 mRNA detectable in brain regions such as the striatum, hippocampus, and olfactory tubercle. The SSTR3 receptor gene maps to human chromosome 22. The existence of at least four distinct human genes encoding somatostatin-14 selective receptors with diverse pharmacological specificities may help to account for some of the multiple biological actions of somatostatin under normal and pathological conditions

Interdependent regulation of intracellular acidification and SHP-1 in apoptosis

UI - 99211499NRC publication: Ye

Caspase-8-mediated intracellular acidification precedes mitochondrial dysfunction in somatostatin-induced apoptosis

NRC publication: Ye

The Occupied Territories Destruction or development? A study of the problems and prospects for economic, social and political development in a context of colonialism

SIGLEGBUnited Kingdo

Decreased 11ß-HSD1 protein level by IGF-I overexpression <i>in vivo</i> and a direct treatment with IGF-I.

<p><b>A</b>. IGF-I overexpression decreased the levels of 11ß-HSD1 in pancreatic islets, liver and visceral fat, shown in Western blots. Wild-type and MT-IGF littermates, 3–4 months old, were sacrificed to isolate pancreatic islets, liver and visceral fat; cell lysates were loaded on blots which were probed against 11β-HSD1 and β-actin. <b>B</b>. The result of Western blot densitometry analysis. Mean ± SE, N = 6, **P<0.01 vs. wild-type islets. <b>C</b>. Decreased 11β-HSD1 protein level caused by direct IGF-I treatment in freshly isolated islets from wild-type mice. Long R3 IGF-I, Sigma-Aldrich, 10 nM or vehicle was added; the islets cells were harvested after 1, 2, or 3 d. The result of Western blotting was corrected with that of β-actin. N = 4, **P<0.01 vs. untreated. <b>D</b>. IGF-I treatment accelerated 11β-HSD1 protein degradation in 11β-HSD1 overexpressing MIN6 cells (as in Figs <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0136656#pone.0136656.g005" target="_blank">5</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0136656#pone.0136656.g006" target="_blank">6</a>). MIN6-HSD1 cells were treated with cycloheximide (10 mg/L) for 2 h before IGF-I (10 nM) or vehicle for 12–48 h. N = 4, **P<0.01 vs. cyclohexmide alone.</p