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https://www.readbyqxmd.com/read/29779013/treatment-of-sec62-over-expressing-tumors-by-thapsigargin-and-trifluoperazine
#1
Christina Körbel, Maximilian Linxweiler, Florian Bochen, Silke Wemmert, Bernhard Schick, Markus Meyer, Hans Maurer, Michael D Menger, Richard Zimmermann, Markus Greiner
Treatment with analogues of the SERCA-inhibitor Thapsigargin is a promising new approach for a wide variety of cancer entities. However, our previous studies on various tumor cells suggested resistance of SEC62 over-expressing tumors to this treatment. Therefore, we proposed the novel concept that e.g. lung-, prostate-, and thyroid-cancer patients should be tested for SEC62 over-expression, and developed a novel therapeutic strategy for a combinatorial treatment of SEC62 over-expressing tumors. The latter was based on the observations that treatment of SEC62 over-expressing tumor cells with SEC62-targeting siRNAs showed less resistance to Thapsigargin as well as a reduction in migratory potential and that the siRNA effects can be mimicked by the Calmodulin antagonist Trifluoperazine...
May 19, 2018: Biomolecular Concepts
https://www.readbyqxmd.com/read/29771714/remifentanil-induces-cardio-protection-against-ischemia-reperfusion-injury-by-inhibiting-endoplasmic-reticulum-stress-through-the-maintenance-of-zinc-homeostasis
#2
Mingwei Sheng, Ge Zhang, Jiannan Wang, Qing Yang, Huanhuan Zhao, Xinxin Cheng, Zhelong Xu
BACKGROUND: Although it is well known that remifentanil (Rem) elicits cardiac protection against ischemia/reperfusion (I/R) injury, the underlying mechanism remains unclear. This study tested if Rem can protect the heart from I/R injury by inhibiting endoplasmic reticulum (ER) stress through the maintenance of zinc (Zn) homeostasis. METHODS: Isolated rat hearts were subjected to 30 minutes of regional ischemia followed by 2 hours of reperfusion. Rem was given by 3 consecutive 5-minute infusions, and each infusion was followed by a 5-minute drug-free perfusion before ischemia...
May 15, 2018: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/29771603/negative-feedback-loop-of-autophagy-and-endoplasmic-reticulum-stress-in-rapamycin-protection-against-renal-ischemia-reperfusion-injury-during-initial-reperfusion-phase
#3
Xinyuan Li, Gongmin Zhu, Xin Gou, Weiyang He, Hubin Yin, Xiaoyu Yang, Jie Li
Rapamycin, an immunosuppressant, is widely used in patients with kidney transplant. However, the therapeutic effects of rapamycin remain controversial. Additionally, previous studies have revealed deleterious effects of rapamycin predominantly when administered for ≥24 h. Few studies, however, have focused on the short-term effects of rapamycin administered only during the initial reperfusion phase. As such, we designed this study to explore the potential effects and mechanisms of rapamycin under a specific therapeutic regimen in which rapamycin is mixed in the perfusate during the initial reperfusion phase (within 24 h)...
May 17, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29765331/high-ph-sensitive-store-operated-ca-2-entry-mediated-by-ca-2-release-activated-ca-2-channels-in-rat-odontoblasts
#4
Maki Kimura, Koichi Nishi, Asuka Higashikawa, Sadao Ohyama, Kaoru Sakurai, Masakazu Tazaki, Yoshiyuki Shibukawa
Odontoblasts play a crucial role in dentin formation and sensory transduction following the application of stimuli to the dentin surface. Various exogenous and endogenous stimuli elicit an increase in the intracellular free calcium concentration ([Ca2+ ]i ) in odontoblasts, which is mediated by Ca2+ release from intracellular Ca2+ stores and/or Ca2+ influx from the extracellular medium. In a previous study, we demonstrated that the depletion of Ca2+ stores in odontoblasts activated store-operated Ca2+ entry (SOCE), a Ca2+ influx pathway...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29764938/redistribution-of-serca-calcium-pump-conformers-during-intracellular-calcium-signaling
#5
Olga N Raguimova, Nikolai Smolin, Elisa Bovo, Siddharth Bhayani, Joseph M Autry, Aleksey V Zima, Seth L Robia
The conformational changes of a calcium transport A TPase were investigated with molecular dynamics (MD) simulations as well as fluorescence resonance energy transfer (FRET) measurements to determine the significance of a discrete structural element for regulation of the conformational dynamics of the transport cycle. Previous MD simulations indicated that a loop in the cytosolic domain of the SERCA calcium transporter facilitates an open-to-closed structural transition. To investigate the significance of this structural element, we performed additional MD simulations and new biophysical measurements of SERCA structure and function...
May 15, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29763601/the-p-s85c-mutation-in-matr3-impairs-stress-granule-formation-in-matrin-3-myopathy
#6
Alexander Mensch, Beate Meinhardt, Nadine Bley, Stefan Hüttelmaier, Ilka Schneider, Gisela Stoltenburg-Didinger, Torsten Kraya, Tobias Müller, Stephan Zierz
Matrin-3-related distal myopathy is characterized mainly by progressive distal weakness of the lower extremities. The mutation p.S85C in matrin-3 (MATR3) has been identified as disease-causing alteration, whereas the specific molecular mechanisms leading to the muscle disease have not been elucidated. In the present study, muscle biopsy samples from six patients and fibroblasts from four patients harboring p.S85C mutation in MATR3 were analyzed. No specific changes in matrin-3 localization or expression were observed...
May 12, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29758225/trpv6-protects-er-stress-induced-apoptosis-via-atf6%C3%AE-trpv6-jnk-pathway-in-human-embryonic-stem-cell-derived-cardiomyocytes
#7
Zhichao Li, Zhaoyue Meng, Jun Lu, Francis M Chen, Wing-Tak Wong, Gary Tse, Changbo Zheng, Wendy Keung, Kennis Tse, Ronald A Li, Liwen Jiang, Xiaoqiang Yao
Human pluripotent stem cell-derived cardiomyocytes have potential applications in disease modeling and drug screening. Therefore, it is important to understand the mechanisms and signaling pathways underlying the survival and death of these cells. Endoplasmic reticulum (ER) stress is triggered by various cellular stresses that disturb protein folding in the ER. Cells cope with ER stress by activating the unfolded protein response (UPR), a homeostatic signaling network that orchestrates the recovery of ER function...
May 11, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29731088/tacrolimus-induced-apoptosis-is-mediated-by-endoplasmic-reticulum-derived-calcium-dependent-caspases-3-12-in-jurkat-cells
#8
Y W Chung, M W Chung, S K Choi, S J Choi, S J N Choi, S Y Chung
Apoptotic signal pathways are delivered to caspase-3, caspase-9, or both in different cells via the death receptor pathway, mitochondrial pathway, or by the endoplasmic reticulum (ER) pathway through initiators of caspase-3, -8, -9, or -12. Tacrolimus (Tac)-induced apoptosis was characterized by nuclear fragmentation and caspase-3 activation. We examined the effect of tacrolimus on ER-derived calcium and caspase-3,-12-mediated apoptosis on Jurkat human T lymphocyte. Tac decreased the viability of Jurkat cells in a dose-dependent manner...
May 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29728739/decreased-contraction-induced-by-endothelium-derived-contracting-factor-in-prolonged-treatment-of-rat-renal-artery-with-endoplasmic-reticulum-stress-inducer
#9
Makoto Ando, Takayuki Matsumoto, Kumiko Taguchi, Tsuneo Kobayashi
Recent evidence suggests that endoplasmic reticulum (ER) stress is involved in the regulation of various physiological functions, including those of the vascular system. However, the relationship between ER stress and vascular function is poorly understood. The endothelial cells control the vascular tone by releasing endothelium-derived relaxing factors and contracting factors (EDCFs). We hypothesized that tunicamycin, an inducer of ER stress, modifies endothelium-dependent contraction and prostaglandins (PGs), a major class of EDCFs, induced contractions in the rat renal artery in rats...
May 4, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29676583/reticulocalbin-3-deficiency-in-alveolar-epithelium-exacerbated-bleomycin-induced-pulmonary-fibrosis
#10
Jiawei Jin, Xiaoqian Shi, Yongchao Li, Qianyu Zhang, Yu Guo, Chaokun Li, Pingping Tan, Qiuhong Fang, Yingmin Ma, Runlin Z Ma
Reticulocalbin 3 (Rcn3) is an endoplasmic reticulum (ER) lumen protein localized to the secretory pathway. We have reported that Rcn3 plays critical role for alveolar epithelial cell type II (AECII) maturation during perinatal lung development, but its biological role in the adult lung is largely unknown. Herein, we found marked induction of Rcn3 expression in alveolar epithelium during bleomycin-induced pulmonary fibrosis, which is most obvious in AECIIs. To further examine Rcn3 in pulmonary injury-remodeling, we generated transgenic mice to selectively delete Rcn3 in AECIIs in adulthood...
April 20, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29672308/modulation-of-pacemaker-potentials-in-murine-small-intestinal-interstitial-cells-of-cajal-by-gamisoyo-san-a-traditional-chinese-herbal-medicine
#11
Doeun Kim, Jung Nam Kim, Joo Hyun Nam, Jong Rok Lee, Sang Chan Kim, Byung Joo Kim
BACKGROUND: The Gamisoyo-san (GSS) has been used for -improving the gastrointestinal (GI) symptoms. The purpose of this study was to investigate the effects of GSS, a traditional Chinese herbal medicine, on the pacemaker potentials of mouse small intestinal interstitial cells of Cajal (ICCs). METHODS: ICCs from the small intestines were dissociated and cultured. Whole-cell patch-clamp configuration was used to record pacemaker potentials and membrane currents. RESULTS: GSS depolarized ICC pacemaker potentials in a dose-dependent manner...
April 19, 2018: Digestion
https://www.readbyqxmd.com/read/29672153/p21-activated-kinase4-in-pancreatic-acini-is-activated-by-gi-hormones-growth-factors-by-novel-signaling-and-is-needed-to-stimulate-secretory-growth-cascades
#12
Irene Ramos-Alvarez, Robert T Jensen
p21-activated kinases(PAKs) are highly conserved serine/threonine protein kinases, which are divided into two groups:Group-I(PAKs1-3) and Group-II(PAKs4-6). In various tissues, Group-II PAKs play important roles in cytoskeletal dynamics, cell growth as well as neoplastic development/progression. However, little is known about Group-II PAKs role in a number of physiological events including their ability to be activated by gastrointestinal(GI) hormones/neurotransmitters/growth-factors(GFs). We used rat pancreatic acini to explore the ability of GI-hormones/neurotransmitters/GFs to activate Group-II-PAKs and the signaling cascades involved...
April 19, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29669320/camkii-potentiates-store-operated-ca2-entry-through-enhancing-stim1-aggregation-and-interaction-with-orai1
#13
Shu Li, Jingyi Xue, Zhipeng Sun, Tiantian Liu, Lane Zhang, Limin Wang, Hongjie You, Zheng Fan, Yuanyuan Zheng, Dali Luo
BACKGROUND/AIMS: Upon Ca2+ store depletion, stromal interaction molecule 1 (STIM1) oligomerizes, redistributes near plasmalemma to interact with Ca2+ selective channel-forming subunit (Orai1) and initiates store-operated Ca2+ entry (SOCE). Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a regulator of SOCE, but how CaMKII regulates SOCE remains obscure. METHODS: Using Fura2, confocal microscopy, co-immunoprecipitation, specific blocker and overexpression/knockdown approaches, we evaluated STIM1 aggregation and its interaction with Orai1, and SOCE upon Ca2+ store depletion in thapsigargin (TG) treated HEK293 and HeLa cells...
April 13, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29666796/plc%C3%AE-induced-ca-2-oscillations-in-mouse-eggs-involve-a-positive-feedback-cycle-of-ca-2-induced-insp-3-formation-from-cytoplasmic-pip-2
#14
Jessica R Sanders, Bethany Ashley, Anna Moon, Thomas E Woolley, Karl Swann
Egg activation at fertilization in mammalian eggs is caused by a series of transient increases in the cytosolic free Ca2+ concentration, referred to as Ca2+ oscillations. It is widely accepted that these Ca2+ oscillations are initiated by a sperm derived phospholipase C isoform, PLCζ that hydrolyses its substrate PIP2 to produce the Ca2+ releasing messenger InsP3 . However, it is not clear whether PLCζ induced InsP3 formation is periodic or monotonic, and whether the PIP2 source for generating InsP3 from PLCζ is in the plasma membrane or the cytoplasm...
2018: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29661866/reciprocal-effects-of-antiretroviral-drugs-used-to-treat-hiv-infection-on-the-fibroblast-growth-factor-21-%C3%AE-klotho-system
#15
Ricardo Moure, Pere Domingo, Joan Villarroya, Laura Gasa, José M Gallego-Escuredo, Tania Quesada-López, Samantha Morón-Ros, Alberto F Maroto, Gracia M Mateo, Joan C Domingo, Francesc Villarroya, Marta Giralt
Following antiretroviral therapy, HIV-infected patients show increased circulating levels of the antidiabetic hormone fibroblast growth factor-21 (FGF21). In contrast, expression of the FGF21-obligatory co-receptor β-Klotho (KLB) is reduced in target tissues. This situation is comparable to the FGF21 resistance status observed in obesity and type-2 diabetes. Here, we performed the first systematic study of the effects of distinct members of different antiretroviral drug classes on the FGF21/KLB system in human hepatic, adipose, and skeletal muscle cells...
April 16, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29661782/doc2b-protects-%C3%AE-cells-against-inflammatory-damage-and-enhances-function
#16
Arianne Aslamy, Eunjin Oh, Erika M Olson, Jing Zhang, Miwon Ahn, Abu Saleh Md Moin, Ragadeepthi Tunduguru, Vishal A Salunkhe, Rajakrishnan Veluthakal, Debbie C Thurmond
Loss of functional β-cell mass is an early feature of type 1 diabetes. To release insulin, β-cells require soluble n-ethylmaleimide-sensitive factor-attachment protein receptor (SNARE) complexes, as well as SNARE complex regulatory proteins like Double C2-domain protein β (DOC2B). We hypothesized that DOC2B deficiency or overabundance may confer susceptibility or protection, respectively, to the functional β-cell mass. Indeed, Doc2b +/- knockout mice show an unusually severe response to multiple-low-dose streptozotocin (MLD-STZ), resulting in more apoptotic β-cells and a smaller β-cell mass...
April 16, 2018: Diabetes
https://www.readbyqxmd.com/read/29619746/tert-enhances-the-survival-rate-of-human-fibroblasts-under-endoplasmic-reticulum-golgi-apparatus-and-lysosomal-stresses
#17
Amer Ali Abd El-Hafeez, Toru Hosoi, Kanako Nakatsu, Mina Thon, Akira Shimamoto, Hidetoshi Tahara, Koichiro Ozawa
OBJECTIVE: The exposure of organelles, such as the endoplasmic reticulum (ER), Golgi apparatus (GA), and lysosomes, to stress activates death mechanisms. Recently, telomerase reverse transcriptase (TERT) has been shown to be involved in cell survival. However, the relationship between TERT and the stress responses is still unclear. Here, we aimed to clarify the possible mechanisms of action through which TERT promotes cell survival by studying its effect on the stresses faced by multiple organelles in human fibroblasts...
April 5, 2018: Biotechnology Letters
https://www.readbyqxmd.com/read/29616815/diastereoselective-synthesis-of-an-advanced-intermediate-of-thapsigargin-and-other-6-12-guaianolides-using-a-rceym-strategy
#18
Morgan Jouanneau, Karunakar Reddy Bonepally, Alan Jeuken, Aurélien Tap, Régis Guillot, Janick Ardisson, Jean-Pierre Férézou, Joëlle Prunet
A new and flexible approach toward the synthesis of 6,12-guaianolide anticancer drugs such as trilobolides or thapsigargin has been developed that could be applied to the preparation of analogues with a modified ring system. The synthesis starts from commercial 2-methylcyclopentane-1,3-dione, only relying on diastereoselective reactions for the construction of the stereogenic centers at C1, C3, C6, and C10 and features a high-yielding ring-closing enyne metathesis (RCEYM) step for the formation of the [5,7] bicyclic core...
April 4, 2018: Organic Letters
https://www.readbyqxmd.com/read/29594285/paeoniflorin-prevents-endoplasmic-reticulum-stress-associated-inflammation-in-lipopolysaccharide-stimulated-human-umbilical-vein-endothelial-cells-via-the-ire1%C3%AE-nf-%C3%AE%C2%BAb-signaling-pathway
#19
Juan Chen, Minghua Zhang, Maomao Zhu, Junfei Gu, Jie Song, Li Cui, Dan Liu, Qing Ning, Xiaobin Jia, Liang Feng
Endoplasmic reticulum (ER) stress-associated inflammation is a critical molecular mechanism involved in the pathogenesis of endothelial dysfunction (ED). Hence, strategies for alleviating ER stress-induced inflammation may be essential for the prevention of cardiovascular diseases. Paeoniflorin (PF), a bioactive compound from Paeonia lactiflora Pallas is known for its functional properties against vascular inflammation. However, to date, PF-mediated protection against ER stress-dependent inflammation has not been identified...
April 25, 2018: Food & Function
https://www.readbyqxmd.com/read/29575057/adiponectin-synthesis-and-secretion-by-subcutaneous-adipose-tissue-is-impaired-during-obesity-by-endoplasmic-reticulum-stress
#20
Ivan Torre-Villalvazo, Ana E Bunt, Gabriela Alemán, Claudia C Marquez-Mota, Andrea Diaz-Villaseñor, Lilia G Noriega, Isabela Estrada, Elizabeth Figueroa-Juárez, Claudia Tovar-Palacio, Leonardo A Rodriguez-López, Patricia López-Romero, Nimbe Torres, Armando R Tovar
Subcutaneous (SAT) and visceral (VAT) adipose tissues stores excess energy as triglycerides and synthesize adiponectin to prevent ectopic lipid accumulation and lipotoxicity. During obesity, an impairment in the capacity of SAT to store triglycerides and synthesize adiponectin is associated with increased free fatty acids (FFA) release, leading to VAT hypertrophy and hepatic and skeletal muscle lipotoxicity. Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) may be involved in SAT dysfunction during obesity...
March 25, 2018: Journal of Cellular Biochemistry
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