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Sigma shRNA

Tzu-Chieh Su, Shu-Hui Lin, Pin-Tse Lee, Shiu-Hwa Yeh, Tsung-Hsun Hsieh, Szu-Yi Chou, Tsung-Ping Su, Jan-Jong Hung, Wen-Chang Chang, Yi-Chao Lee, Jian-Ying Chuang
The accumulation of reactive oxygen species (ROS) have implicated the pathogenesis of several human diseases including neurodegenerative disorders, stroke, and traumatic brain injury, hence protecting neurons against ROS is very important. In this study, we focused on sigma-1 receptor (Sig-1R), a chaperone at endoplasmic reticulum, and investigated its protective functions. Using hydrogen peroxide (H2O2)-induced ROS accumulation model, we verified that apoptosis-signaling pathways were elicited by H2O2 treatment...
June 2016: Neuropharmacology
Hanne B Moeller, Joachim Slengerik-Hansen, Takwa Aroankins, Mette Assentoft, Nanna MacAulay, Soeren K Moestrup, Vivek Bhalla, Robert A Fenton
The 14-3-3 family of proteins are multifunctional proteins that interact with many of their cellular targets in a phosphorylation-dependent manner. Here, we determined that 14-3-3 proteins interact with phosphorylated forms of the water channel aquaporin-2 (AQP2) and modulate its function. With the exception of σ, all 14-3-3 isoforms were abundantly expressed in mouse kidney and mouse kidney collecting duct cells (mpkCCD14). Long-term treatment of mpkCCD14 cells with the type 2 vasopressin receptor agonist dDAVP increased mRNA and protein levels of AQP2 alongside 14-3-3β and -ζ, whereas levels of 14-3-3η and -θ were decreased...
January 29, 2016: Journal of Biological Chemistry
G Cristina Brailoiu, Elena Deliu, Linda M Console-Bram, Jonathan Soboloff, Mary E Abood, Ellen M Unterwald, Eugen Brailoiu
Sigma-1 receptor (Sig-1R) is an intracellular chaperone protein with many ligands, located at the endoplasmic reticulum (ER). Binding of cocaine to Sig-1R has previously been found to modulate endothelial functions. In the present study, we show that cocaine dramatically inhibits store-operated Ca(2+) entry (SOCE), a Ca(2+) influx mechanism promoted by depletion of intracellular Ca(2+) stores, in rat brain microvascular endothelial cells (RBMVEC). Using either Sig-1R shRNA or pharmacological inhibition with the unrelated Sig-1R antagonists BD-1063 and NE-100, we show that cocaine-induced SOCE inhibition is dependent on Sig-1R...
January 1, 2016: Biochemical Journal
Mireille Happy, Jordan Dejoie, Cynthia K Zajac, Briseida Cortez, Karabi Chakraborty, Joseph Aderemi, Moira Sauane
Over the last years, many improvements have been made in the treatment of breast cancer; however, novel and less toxic therapies are still needed, especially for relapsing and chemo-resistant patients. Here, we analyzed the therapeutic potential of p53 and Rimcazole, a Sigma 1 Receptor antagonist. Rimcazole and p53 are being evaluated in preclinical and clinical trials, respectively. While p53 is a promising antitumor therapeutic agent, antagonists of Sigma 1 Receptor also inhibit tumor cell survival and induce apoptosis...
January 9, 2015: Biochemical and Biophysical Research Communications
Heng-Xing Zhou, Xue-Ying Li, Fu-Yuan Li, Chang Liu, Zhi-Pin Liang, Shen Liu, Bin Zhang, Tian-Yi Wang, Tian-Ci Chu, Lu Lu, Guang-Zhi Ning, Xiao-Hong Kong, Shi-Qing Feng
After spinal cord injury (SCI), the rapidly upregulated chondroitin sulfate proteoglycans (CSPGs), the prominent chemical constituents and main repulsive factors of the glial scar, play an important role in the extremely limited ability to regenerate in adult mammals. Although many methods to overcome the inhibition have been tested, no successful method with clinical feasibility has been devised to date. It was recently discovered that receptor protein tyrosine phosphatase sigma (RPTPσ) is a functional receptor for CSPGs-mediated inhibition...
October 24, 2014: Brain Research
J Prause, A Goswami, I Katona, A Roos, M Schnizler, E Bushuven, A Dreier, S Buchkremer, S Johann, C Beyer, M Deschauer, D Troost, J Weis
Intracellular accumulations of mutant, misfolded proteins are major pathological hallmarks of amyotrophic lateral sclerosis (ALS) and related disorders. Recently, mutations in Sigma receptor 1 (SigR1) have been found to cause a form of ALS and frontotemporal lobar degeneration (FTLD). Our goal was to pinpoint alterations and modifications of SigR1 in ALS and to determine how these changes contribute to the pathogenesis of ALS. In the present study, we found that levels of the SigR1 protein were reduced in lumbar ALS patient spinal cord...
April 15, 2013: Human Molecular Genetics
John R Hornick, Suwanna Vangveravong, Dirk Spitzer, Carmen Abate, Francesco Berardi, Peter Goedegebuure, Robert H Mach, William G Hawkins
BACKGROUND: Sigma-2 receptor ligands have been studied for treatment of pancreatic cancer because they are preferentially internalized by proliferating cells and induce apoptosis. This mechanism of apoptosis is poorly understood, with varying reports of caspase-3 dependence. We evaluated multiple sigma-2 receptor ligands in this study, each shown to decrease tumor burden in preclinical models of human pancreatic cancer. RESULTS: Fluorescently labeled sigma-2 receptor ligands of two classes (derivatives of SW43 and PB282) localize to cell membrane components in Bxpc3 and Aspc1 pancreatic cancer cells and accumulate in lysosomes...
2012: Journal of Experimental & Clinical Cancer Research: CR
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