Stearate‐Induced Apoptosis in Human Pancreatic β‐Cells is Associated with Changes in Membrane Protein Expression and These Changes are Inhibited by Oleate

2019 ◽  
Vol 13 (4) ◽  
pp. 1800104 ◽  
Author(s):  
Vlasta Němcová‐Fürstová ◽  
Kamila Balušíková ◽  
Petr Halada ◽  
Nela Pavlíková ◽  
Jan Šrámek ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Protein Expression ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Membrane Protein Expression ◽  
Induced Apoptosis

scholarly journals HM-Chromanone Isolated from Portulaca oleracea L. Protects INS-1 Pancreatic β Cells against Glucotoxicity-Induced Apoptosis

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 404 ◽  
Author(s):  
Jae Eun Park ◽  
Youngwan Seo ◽  
Ji Sook Han
Keyword(s):  
Protein Expression ◽  
Cell Viability ◽  
High Glucose ◽  
Annexin V ◽  
Thiobarbituric Acid ◽  
Portulaca Oleracea ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Induced Apoptosis ◽  
High Level

In this study, we investigated whether (E)-5-hydroxy-7-methoxy-3-(2′-hydroxybenzyl)-4-chromanone, a homoisoflavonoid compound isolated from Portulaca oleracea L., protects INS-1 pancreatic β cells against glucotoxicity-induced apoptosis. Treatment with high glucose (30 mM) induced apoptosis in INS-1 pancreatic β cells; however, the level of cell viability was significantly increased by treatment with (E)-5-hydroxy-7-methoxy-3-(2′-hydroxybenzyl)-4-chromanone. Treatment with 10–20 µM of (E)-5-hydroxy-7-methoxy-3-(2′-hydroxybenzyl)-4-chromanone dose-dependently increased cell viability and significantly decreased the intracellular level of reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS), and nitric oxide levels in INS-1 pancreatic β cells pretreated with high glucose. These effects were associated with increased anti-apoptotic Bcl-2 protein expression, while reducing pro-apoptotic Bax, cytochrome C, and caspase 9 protein expression. Treatment with (E)-5-hydroxy-7-methoxy-3-(2′-hydroxybenzyl)-4-chromanone reduced the apoptosis previously induced by high-level glucose-treatment, according to annexin V/propidium iodide staining. These results demonstrate that (E)-5-hydroxy-7-methoxy-3-(2′-hydroxybenzyl)-4-chromanone may be useful as a potential therapeutic agent to protect INS-1 pancreatic β cells against high glucose-induced apoptosis.

scholarly journals Long-Term Exposure of Pancreatic β-Cells to Palmitate Results in SREBP-1C-Dependent Decreases in GLP-1 Receptor Signaling via CREB and AKT and Insulin Secretory Response

Endocrinology ◽  
2016 ◽  
Vol 157 (6) ◽  
pp. 2243-2258 ◽  
Author(s):  
Annalisa Natalicchio ◽  
Giuseppina Biondi ◽  
Nicola Marrano ◽  
Rossella Labarbuta ◽  
Federica Tortosa ◽  
...  
Keyword(s):  
Protein Expression ◽  
Insulin Release ◽  
Binding Protein ◽  
Camp Response Element Binding ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Camp Response Element ◽  
Element Binding Protein ◽  
Viral Oncogene Homolog ◽  
Erk Kinase

The effects of prolonged exposure of pancreatic β-cells to high saturated fatty acids on glucagon-like peptide-1 (GLP-1) action were investigated. Murine islets, human pancreatic 1.1B4 cells, and rat INS-1E cells were exposed to palmitate for 24 hours. mRNA and protein expression/phosphorylation were measured by real-time RT-PCR and immunoblotting, respectively. Specific short interfering RNAs were used to knockdown expression of the GLP-1 receptor (Glp1r) and Srebf1. Insulin release was assessed with a specific ELISA. Exposure of murine islets, as well as of human and INS-1E β-cells, to palmitate reduced the ability of exendin-4 to augment insulin mRNA levels, protein content, and release. In addition, palmitate blocked exendin-4-stimulated cAMP-response element-binding protein and v-akt murine thymoma viral oncogene homolog phosphorylation, whereas phosphorylation of MAPK-ERK kinase-1/2 and ERK-1/2 was not altered. Similarly, RNA interference-mediated suppression of Glp1r expression prevented exendin-4-induced cAMP-response element-binding protein and v-akt murine thymoma viral oncogene homolog phosphorylation, but did not impair exendin-4 stimulation of MAPK-ERK kinase-1/2 and ERK-1/2. Both islets from mice fed a high fat diet and human and INS-1E β-cells exposed to palmitate showed reduced GLP-1 receptor and pancreatic duodenal homeobox-1 (PDX-1) and increased sterol regulatory element-binding protein (SREBP-1C) mRNA and protein levels. Furthermore, suppression of SREBP-1C protein expression prevented the reduction of PDX-1 and GLP-1 receptor levels and restored exendin-4 signaling and action. Finally, treatment of INS-1E cells with metformin for 24 h resulted in inhibition of SREBP-1C expression, increased PDX-1 and GLP-1 receptor levels, consequently, enhancement of exendin-4-induced insulin release. Palmitate impairs exendin-4 effects on β-cells by reducing PDX-1 and GLP-1 receptor expression and signaling in a SREBP-1C-dependent manner. Metformin counteracts the impairment of GLP-1 receptor signaling induced by palmitate.

Quantitative Membrane Protein Expression at the Blood–Brain Barrier of Adult and Younger Cynomolgus Monkeys

2011 ◽  
Vol 100 (9) ◽  
pp. 3939-3950 ◽  
Author(s):  
Katsuaki Ito ◽  
Yasuo Uchida ◽  
Sumio Ohtsuki ◽  
Sanshiro Aizawa ◽  
Hirotaka Kawakami ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Protein Expression ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Cynomolgus Monkeys ◽  
Membrane Protein Expression ◽  
Blood Brain

scholarly journals Sex Hormones Regulate Rat Hepatic Monocarboxylate Transporter Expression and Membrane Trafficking

2017 ◽  
Vol 20 (1) ◽  
pp. 435 ◽  
Author(s):  
Jieyun Cao ◽  
Michael Ng ◽  
Melanie A Felmlee
Keyword(s):  
Sex Differences ◽  
Membrane Protein ◽  
Protein Expression ◽  
Estrous Cycle ◽  
Sex Hormones ◽  
Membrane Trafficking ◽  
Drug Disposition ◽  
Membrane Expression ◽  
Membrane Protein Expression ◽  
Estrous Cycle Stage

Purpose: Monocarboxylate transporters (MCTs) are involved in the transport of monocarboxylates such as ketone bodies, lactate, and pharmaceutical agents. CD147 functions as an ancillary protein for MCT1 and MCT4 for plasma membrane trafficking. Sex differences in MCT1 and MCT4 have been observed in muscle and reproductive tissues; however, there is a paucity of information on MCT sex differences in tissues involved in drug disposition. The objective of the present study was to quantify hepatic MCT1, MCT4 and CD147 mRNA, total cellular and membrane protein expression in males, over the estrous cycle in females and in ovariectomized (OVX) females. Method: Liver samples were collected from females at the four estrous cycle stages (proestrus, estrus, metestrus, diestrus), OVX females and male Sprague-Dawley rats (N = 3 – 5). Estrus cycle stage of females was determined by vaginal lavage. mRNA and protein (total and membrane) expression of MCT1, MCT4 and CD147 was evaluated by qPCR and western blot analysis. Results: MCT1 mRNA and membrane protein expression varied with estrous cycle stage, with OVX females having higher expression than males, indicating that female sex hormones may play a role in MCT1 regulation. MCT4 membrane expression varied with estrous cycle stage with expression significantly lower than males. MCT4 membrane expression in OVX females was also lower than males, suggesting that androgens play a role in membrane expression of MCT4. Males had higher membrane CD147 expression, whereas there was no difference in whole cell protein and mRNA levels suggesting that androgens are involved in regulating CD147 membrane localization. Conclusions: This study demonstrates hepatic expression and membrane localization of MCT1, MCT4 and CD147 are regulated by sex hormones. Sex differences in hepatic MCT expression may lead to altered drug disposition, so it is critical to elucidate the underlying mechanisms in the sex hormone-dependent regulation of MCT expression. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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