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https://www.readbyqxmd.com/read/28906486/small-molecule-rl71-triggered-excessive-autophagic-cell-death-as-a-potential-therapeutic-strategy-in-triple-negative-breast-cancer
#1
Jian Gao, Minmin Fan, Shuang Peng, Minxia Zhang, Gang Xiang, Xin Li, Wenjie Guo, Yang Sun, Xuefeng Wu, Xudong Wu, Guang Liang, Yan Shen, Qiang Xu
Triple-negative breast cancer (TNBC) has an aggressive phenotype and a poor prognosis owing to the high propensity for metastatic progression and the absence of specific targeted treatment. Here, we revealed that small-molecule RL71 targeting sarco/endoplasmic reticulum calcium-ATPase 2 (SERCA2) exhibited potent anti-cancer activity on all TNBC cells tested. Apart from apoptosis induction, RL71 triggered excessive autophagic cell death, the main contributor to RL71-induced TNBC cell death. RL71 augmented the release of Ca(2+) from the endoplasmic reticulum (ER) into the cytosol by inhibiting SERCA2 activity...
September 14, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28903365/protective-effects-of-circulating-microvesicles-derived-from-myocardial-ischemic-rats-on-apoptosis-of-cardiomyocytes-in-myocardial-ischemia-reperfusion-injury
#2
Yao Wang, Su Wei, Yi-Lu Wang, Miao Liu, Man Shang, Qi Zhang, Yan-Na Wu, Ming-Lin Liu, Jun-Qiu Song, Yan-Xia Liu
OBJECTIVE: To investigate the effects of circulating microvesicles derived from myocardial ischemia (I-MVs) on apoptosis in myocardial ischemia/reperfusion (I/R) injury in rats. METHODS: I-MVs from rats undergoing myocardial left anterior descending (LAD) coronary artery ligation were isolated by ultracentrifugation from circulating blood and characterized by flow cytometry. I-MVs were administered intravenously (4.8 mg/kg) at 5 min before reperfusion procedure in I/R injury model which was induced by 30-min of ischemia and 120-min of reperfusion of LAD in rats...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28890335/the-er-localized-transmembrane-protein-epg-3-vmp1-regulates-serca-activity-to-control-er-isolation-membrane-contacts-for-autophagosome-formation
#3
Yan G Zhao, Yong Chen, Guangyan Miao, Hongyu Zhao, Wenyan Qu, Dongfang Li, Zheng Wang, Nan Liu, Lin Li, She Chen, Pingsheng Liu, Du Feng, Hong Zhang
During autophagosome formation in mammalian cells, isolation membranes (IMs; autophagosome precursors) dynamically contact the ER. Here, we demonstrated that the ER-localized metazoan-specific autophagy protein EPG-3/VMP1 controls ER-IM contacts. Loss of VMP1 causes stable association of IMs with the ER, thus blocking autophagosome formation. Interaction of WIPI2 with the ULK1/FIP200 complex and PI(3)P contributes to the formation of ER-IM contacts, and these interactions are enhanced by VMP1 depletion. VMP1 controls contact formation by promoting SERCA (sarco[endo]plasmic reticulum calcium ATPase) activity...
September 6, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28889229/melatonin-alleviates-inflammation-induced-apoptosis-in-human-umbilical-vein-endothelial-cells-via-suppression-of-ca-2-xo-ros-drp1-mitochondrial-fission-axis-by-activation-of-ampk-serca2a-pathway
#4
Jiasen Cui, Zeng Li, Shunjiu Zhuang, Shaohong Qi, Li Li, Junwen Zhou, Wan Zhang, Yun Zhao
Endothelia inflammation damage is vital to the development and progression of chronic venous disease. In the present study, we explored the protective effect of melatonin on endothelia apoptosis induced by LPS, particularly focusing on the mitochondrial fission. We demonstrated that human umbilical vein endothelial cells (HUVEC) subjected to LPS for 12 h exhibited a higher apoptotic rate. However, melatonin (1-20 μM) treatment 12 h before LPS had the ability to protect HUVEC cell against LPS-mediated apoptosis in a dose-dependent manner...
September 9, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28884444/the-ccaat-box-in-the-proximal-serca2-gene-promoter-regulates-basal-and-stress-induced-transcription-in-cardiomyocytes
#5
Jorge Fragoso-Medina, Gabriela Rodriguez, Angel Zarain-Herzberg
The cardiac sarco/endoplasmic reticulum Ca(2+)-ATPase-2a (SERCA2a) is vital for the correct handling of calcium concentration in cardiomyocytes. Recent studies showed that the induction of endoplasmic reticulum (ER) stress (ERS) with the SERCA2 inhibitor Thapsigargin (Tg) increases the mRNA and protein levels of SERCA2a. The SERCA2 gene promoter contains an ERS response element (ERSE) at position -78 bp that is conserved among species and might transcriptionally regulate SERCA2 gene expression. However, its involvement in SERCA2 basal and calcium-mediated transcriptional activation has not been elucidated...
September 7, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28878117/tead1-is-required-for-maintaining-adult-cardiomyocyte-function-and-its-loss-results-in-lethal-dilated-cardiomyopathy
#6
Ruya Liu, Jeongkyung Lee, Byung S Kim, Qiongling Wang, Samuel K Buxton, Nikhil Balasubramanyam, Jean J Kim, Jianrong Dong, Aijun Zhang, Shumin Li, Anisha A Gupte, Dale J Hamilton, James F Martin, George G Rodney, Cristian Coarfa, Xander Ht Wehrens, Vijay K Yechoor, Mousumi Moulik
Heart disease remains the leading cause of death worldwide, highlighting a pressing need to identify novel regulators of cardiomyocyte (CM) function that could be therapeutically targeted. The mammalian Hippo/Tead pathway is critical in embryonic cardiac development and perinatal CM proliferation. However, the requirement of Tead1, the transcriptional effector of this pathway, in the adult heart is unknown. Here, we show that tamoxifen-inducible adult CM-specific Tead1 ablation led to lethal acute-onset dilated cardiomyopathy, associated with impairment in excitation-contraction coupling...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28874726/remarkable-plasticity-of-na-k-atpase-ca-2-atpase-and-serca-contributes-to-muscle-disuse-atrophy-resistance-in-hibernating-daurian-ground-squirrels
#7
Quanling Guo, Xin Mi, Xiaoyong Sun, Xiaoyu Li, Weiwei Fu, Shenhui Xu, Qi Wang, Yasir Arfat, Huiping Wang, Hui Chang, Yunfang Gao
We investigated cytosolic calcium (Ca(2+)) and sarcoplasmic reticulum Ca(2+) regulation in skeletal muscle fibers of hibernating Daurian ground squirrels (Spermophilus dauricus), non-hibernating hindlimb-unloaded (HLU) squirrels, and HLU rats to clarify the molecular mechanisms involved in preventing muscle atrophy in hibernators. The Na(+), K(+)-ATPase and Ca(2+)-ATPase activities in the soleus muscle (SOL) of squirrels were maintained in hibernation, decreased during interbout arousal (IB-A), and increased to autumn/pre-hibernation (AUT/Pre-H) levels in torpor after interbout arousal (Post-IBA), whereas activities in the extensor digitorum longus muscle (EDL) were stable during hibernation, but increased during post-hibernation (Post-H)...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28874462/%C3%AE-arrestin2-improves-post-myocardial-infarction-heart-failure-via-sarco-endo-plasmic-reticulum-ca-2-atpase-dependent-positive-inotropy-in-cardiomyocytes
#8
Katie A McCrink, Jennifer Maning, Angela Vu, Malika Jafferjee, Christine Marrero, Ava Brill, Ashley Bathgate-Siryk, Samalia Dabul, Walter J Koch, Anastasios Lymperopoulos
Heart failure is the leading cause of death in the Western world, and new and innovative treatments are needed. The GPCR (G protein-coupled receptor) adapter proteins βarr (β-arrestin)-1 and βarr-2 are functionally distinct in the heart. βarr1 is cardiotoxic, decreasing contractility by opposing β1AR (adrenergic receptor) signaling and promoting apoptosis/inflammation post-myocardial infarction (MI). Conversely, βarr2 inhibits apoptosis/inflammation post-MI but its effects on cardiac function are not well understood...
September 5, 2017: Hypertension
https://www.readbyqxmd.com/read/28869833/yap-promotes-hepatocellular-carcinoma-metastasis-and-mobilization-via-governing-cofilin-f-actin-lamellipodium-axis-by-regulation-of-jnk-bnip3-serca-camkii-pathways
#9
Chen Shi, Yong Cai, Yongheng Li, Ye Li, Nan Hu, Sai Ma, Shunying Hu, Pingjun Zhu, Weihu Wang, Hao Zhou
Despite the increasingly important role of Hippo-Yap in hepatocellular carcinoma (HCC) development and progression, little insight is available at the time regarding the specifics interaction of Yap and cancer cells migration. Here, we identified the mechanism by which tumor-intrinsic Yap deletion resulted in HCC migratory inhibition. Yap was greatly upregulated in HCC and its expression promoted the cells migration. Functional studies found that knockdown of Yap induced JNK phosphorylation which closely bound to the Bnip3 promoter and contributed to Bnip3 expression...
August 24, 2017: Redox Biology
https://www.readbyqxmd.com/read/28855109/the-vasorelaxant-effect-of-mitiglinide-via-activation-of-voltage-dependent-k-channels-and-serca-pump-in-aortic-smooth-muscle
#10
Hongliang Li, Hye Won Kim, Sung Eun Shin, Mi Seon Seo, Jin Ryeol An, Kwon-Soo Ha, Eun-Taek Han, Seok-Ho Hong, Amy L Firth, Il-Whan Choi, Il Yong Han, Dae-Sung Lee, Mi-Jin Yim, Won Sun Park
AIMS: The vasorelaxant effects of the anti-diabetic drug, mitiglinide in phenylephrine (Phe)-pre-contracted aortic rings were examined. MATERIALS AND METHODS: Arterial tone measurement was performed in aortic smooth muscle cells. KEY FINDINGS: Mitiglinide dose-dependently induced vasorelaxation. Application of the large-conductance Ca(2+)-activated K(+) (BKCa) channel blocker paxilline, inwardly rectifying K(+) (Kir) channel blocker Ba(2+), and ATP-sensitive K(+) (KATP) channel blocker glibenclamide did not affect the vasorelaxant effect of mitiglinide...
August 27, 2017: Life Sciences
https://www.readbyqxmd.com/read/28852583/comparative-molecular-analyses-of-select-ph-and-osmoregulatory-genes-in-three-freshwater-crayfish-cherax-quadricarinatus-c-destructor-and-c-cainii
#11
Muhammad Y Ali, Ana Pavasovic, Lalith K Dammannagoda, Peter B Mather, Peter J Prentis
Systemic acid-base balance and osmotic/ionic regulation in decapod crustaceans are in part maintained by a set of transport-related enzymes such as carbonic anhydrase (CA), Na(+)/K(+)-ATPase (NKA), H(+)-ATPase (HAT), Na(+)/K(+)/2Cl(-) cotransporter (NKCC), Na(+)/Cl(-)/HCO[Formula: see text] cotransporter (NBC), Na(+)/H(+) exchanger (NHE), Arginine kinase (AK), Sarcoplasmic Ca(+2)-ATPase (SERCA) and Calreticulin (CRT). We carried out a comparative molecular analysis of these genes in three commercially important yet eco-physiologically distinct freshwater crayfish, Cherax quadricarinatus, C...
2017: PeerJ
https://www.readbyqxmd.com/read/28844112/reactive-oxygen-species-produced-by-a-photodynamic-effect-induced-calcium-signal-in-neurons-and-astrocytes
#12
Maria Neginskaya, Elena Berezhnaya, Anatoly B Uzdensky, Andrey Y Abramov
Photodynamic therapy (PDT) leads to production of reactive oxygen species (ROS) and cell destruction due to oxidative stress. We used photodynamic effect of photosensitizer radachlorin to unravel the effect of photo-induced oxidative stress on the calcium signal and lipid peroxidation in primary culture of cortical neurons and astrocytes using live cell imaging. We have found that irradiation in presence of 200 nM of radachlorin induces calcium signal in primary neurons and astrocytes. Photo-induced neuronal calcium signal depends on internal calcium stores as it was still observed in calcium-free medium and could be blocked by depletion of endoplasmic reticulum (ER) stores with inhibitor of sarco-endoplasmic reticulum Ca(2+) ATPase (SERCA) thapsigargin...
August 26, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28822538/smooth-muscle-nitric-oxide-responsiveness-and-clinical-maturation-of-hemodialysis-arteriovenous-fistulae
#13
Xiaoyong Tong, Xiuyun Hou, Christopher Wason, Tal Kopel, Richard A Cohen, Laura M Dember
The arteriovenous fistula is the preferred type of hemodialysis vascular access for patients with end-stage renal disease, but a high proportion of newly created fistulas fail to mature for use. Stenosis caused by neointimal hyperplasia often is present in fistulas with maturation failure, suggesting that local mechanisms controlling vascular smooth muscle cell (SMC) migration and proliferation are important contributors to maturation failure. SMCs cultured from explants of vein tissue obtained at the time of fistula creation from 19 patients with end-stage renal disease were studied to determine whether smooth muscle responsiveness to nitric oxide is associated with fistula maturation outcomes...
September 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28821490/serca-directs-cell-migration-and-branching-across-species-and-germ-layers
#14
Danielle V Bower, Nick Lansdale, Sonia Navarro, Thai V Truong, Dan J Bower, Neil C Featherstone, Marilyn G Connell, Denise Al-Alam, Mark R Frey, Le A Trinh, G Esteban Fernandez, David Warburton, Scott E Fraser, Daimark Bennett, Edwin C Jesudason
Branching morphogenesis underlies organogenesis in vertebrates and invertebrates, yet is incompletely understood. Here, we show that the sarco-endoplasmic reticulum Ca(2+) reuptake pump (SERCA) directs budding across germ layers and species. Clonal knockdown demonstrated a cell-autonomous role for SERCA in Drosophila air sac budding. Live imaging of Drosophila tracheogenesis revealed elevated Ca(2+) levels in migratory tip cells as they form branches. SERCA blockade abolished this Ca(2+) differential, aborting both cell migration and new branching...
August 17, 2017: Biology Open
https://www.readbyqxmd.com/read/28819266/amalaki-rasayana-a-traditional-indian-drug-enhances-cardiac-mitochondrial-and-contractile-functions-and-improves-cardiac-function-in-rats-with-hypertrophy
#15
Vikas Kumar, Kumar A Aneesh, K Kshemada, Kumar G S Ajith, Raj S S Binil, Neha Deora, G Sanjay, A Jaleel, T S Muraleedharan, E M Anandan, R S Mony, M S Valiathan, Kumar T R Santhosh, C C Kartha
We evaluated the cardioprotective effect of Amalaki Rasayana (AR), a rejuvenating Ayurvedic drug prepared from Phyllanthus emblica fruits in the reversal of remodeling changes in pressure overload left ventricular cardiac hypertrophy (LVH) and age-associated cardiac dysfunction in male Wistar rats. Six groups (aging groups) of 3 months old animals were given either AR or ghee and honey (GH) orally; seventh group was untreated. Ascending aorta was constricted using titanium clips in 3 months old rats (N = 24; AC groups) and after 6 months, AR or GH was given for further 12 months to two groups; one group was untreated...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819051/the-effects-of-8-weeks-voluntary-wheel-running-on-the-contractile-performance-of-isolated-locomotory-soleus-and-respiratory-diaphragm-skeletal-muscle-during-early-ageing
#16
Jason Tallis, Matthew F Higgins, Frank Seebacher, Val M Cox, Michael J Duncan, Rob S James
Decreased skeletal muscle performance with increasing age is strongly associated with reduced mobility and quality of life. Increased physical activity is a widely prescribed method of reducing the detrimental effects of ageing on skeletal muscle contractility. The present study uses isometric and work loop testing protocols to uniquely investigate the effects of 8 weeks of voluntary wheel running on the contractile performance of isolated dynapenic soleus and diaphragm muscles of 38 week old CD1 mice. When compared to untrained controls, voluntary wheel running induced significant improvements in maximal isometric stress and work loop power, a reduced resistance to fatigue, but greater cumulative work during fatiguing work loop contractions in isolated muscle...
August 17, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28811460/prevention-of-atrial-fibrillation-by-using-sarcoplasmic-reticulum-calcium-atpase-pump-overexpression-in-a-rabbit-model-of-rapid-atrial-pacing
#17
Hong Li Wang, Xian Hui Zhou, Zhi Qiang Li, Ping Fan, Qi Na Zhou, Yao Dong Li, Yue Mei Hou, Bao Peng Tang
BACKGROUND Recent research suggests that abnormal Ca2+ handling plays a role in the occurrence and maintenance of atrial fibrillation (AF). Therefore, Ca2+ release and ingestion depend on properties of the ryanodine receptor (RyR) and sarcoplasmic reticulum Ca2+ATPase2a (SERCA2a). This study aimed to detect whether SERCA2a gene overexpression has a preventive effect on atrial fibrillation caused by rapid pacing right atrium. MATERIAL AND METHODS Forty-eight New Zealand white rabbits were randomly divided into a control group, AF group, AAV9/GFP group, and AAV9/SERCA2a group...
August 16, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28807154/total-internal-reflectance-fluorescence-imaging-of-genetically-engineered-ryanodine-receptor-targeted-ca-2-probes-in-rat-ventricular-myocytes
#18
Sara Pahlavan, Marin Morad
The details of cardiac Ca(2+) signaling within the dyadic junction remain unclear because of limitations in rapid spatial imaging techniques, and availability of Ca(2+) probes localized to dyadic junctions. To critically monitor ryanodine receptors' (RyR2) Ca(2+) nano-domains, we combined the use of genetically engineered RyR2-targeted pericam probes, (FKBP-YCaMP, Kd=150nM, or FKBP-GCaMP6, Kd=240nM) with rapid total internal reflectance fluorescence (TIRF) microscopy (resolution, ∼80nm). The punctate z-line patterns of FKBP,(2)-targeted probes overlapped those of RyR2 antibodies and sharply contrasted to the images of probes targeted to sarcoplasmic reticulum (SERCA2a/PLB), or cytosolic Fluo-4 images...
September 2017: Cell Calcium
https://www.readbyqxmd.com/read/28803243/lithium-sensitivity-of-store-operated-ca2-entry-and-survival-of-fibroblasts-isolated-from-chorea-acanthocytosis-patients
#19
Lisann Pelzl, Bhaeldin Elsir, Itishri Sahu, Rosi Bissinger, Yogesh Singh, Basma Sukkar, Sabina Honisch, Ludger Schoels, Mohamed Jemaà, Elisabeth Lang, Alexander Storch, Andreas Hermann, Christos Stournaras, Florian Lang
BACKGROUND: The widely expressed protein chorein fosters activation of the phosphoinositide 3 kinase (PI3K) pathway thus supporting cell survival. Loss of function mutations of the chorein encoding gene VPS13A (vacuolar protein sorting-associated protein 13A) causes chorea-acanthocytosis (ChAc), a neurodegenerative disorder paralleled by deformations of erythrocytes. In mice, genetic knockout of chorein leads to enhanced neuronal apoptosis. PI3K dependent signalling upregulates Orai1, a pore forming channel protein accomplishing store operated Ca2+ entry (SOCE)...
August 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28801956/evidence-of-er-stress-and-upr-activation-in-patients-with-brody-disease-and-brody-syndrome
#20
V Guglielmi, N C Voermans, A Oosterhof, D Nowis, B G van Engelen, G Tomelleri, G Vattemi
Brody disease (BD, OMIM #601003) is an inherited skeletal muscle disease clinically characterized by exercise-induced impairment of muscle relaxation and stiffness due to the delay in the Ca(2+) re-uptake in the sarcoplasmic reticulum (SR)[1, 2]. The delayed muscle relaxation mainly affects legs, harms, hands and eyelids and usually improves after a few minutes rest [1-3]. Patients frequently report myalgia, painless or mildly painful cramps whereas recurrent rhabdomyolysis have been described in a few cases [2, 3]...
August 12, 2017: Neuropathology and Applied Neurobiology
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