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Shunying Hu, Pingjun Zhu, Hao Zhou, Ying Zhang, Yundai Chen
BACKGROUND: Melatonin is a neuroendocrine hormone synthesized primarily by the pineal gland that is indicated to effectively prevent myocardial reperfusion injury. It is unclear whether melatonin protects cardiac function from reperfusion injury by modulating intracellular calcium homeostasis. OBJECTIVE: Demonstrate that melatonin protect against myocardial reperfusion injury through modulating IP3R and SERCA2a to maintain calcium homeostasis via activation of ERK1 in cardiomyocytes...
January 2018: Arquivos Brasileiros de Cardiologia
Pavel Montes de Oca Balderas, Horacio Montes de Oca Balderas
Background: Astrocytes were conceived for decades only as supporting cells of the brain. However, the observation of Ca2+ waves in astrocyte synctitia, their neurotransmitter receptor expression and gliotransmitter secretion suggested a role in information handling, conception that has some controversies. Synaptic Neuron-Astrocyte metabotropic communication mediated by Inositol tris-phosphate (SN-AmcIP3) is supported by different reports. However, some models contradict this idea and Ca2+ stores are 1000 ± 325 nm apart from the Postsynaptic Density in the Perisynaptic Astrocyte Projections (PAP's), suggesting that SN-AmcIP3 is extrasynaptic...
2018: BMC Biophysics
Kashi Raj Bhattarai, Raghupatil Junjappa, Mallikarjun Handigund, Hyung-Ryong Kim, Han-Jung Chae
Xerostomia is a state of oral dryness associated with salivary gland dysfunction and is induced by stress, radiation and chemical therapy, various systemic and autoimmune diseases, and specific medications. Fluid secretion is interrupted by the stimulation of neurotransmitter-induced increase in cytosolic calcium ([Ca 2+ ] i ) in salivary gland acinar cells, prompting the mobilization of ion channels and their transporters. Salivary fluid and protein secretion are principally dependent on parasympathetic and sympathetic nerves...
February 8, 2018: Autoimmunity Reviews
Yung Sing Ch'ng, Yean Chun Loh, Chu Shan Tan, Mariam Ahmad, Mohd Zaini Asmawi, Wan Maznah Wan Omar, Mun Fei Yam
The seeds of Swietenia macrophylla King (SM) (Meliaceae) are used as a folk medicine for the treatment of hypertension in Malaysia. However, the antihypertensive and vasorelaxant effects of SM seeds are still not widely studied. Thus, this study was designed to investigate the in vivo antihypertensive effects and in vitro mechanism of vasorelaxation of a 50% ethanolic SM seed extract (SM50) and the fingerprint of SM50 was developed through tri-step Fourier transform infrared (FTIR) spectroscopy. The vasorelaxant activity and the underlying mechanisms of SM50 were evaluated on thoracic aortic rings isolated from Sprague-Dawley rats in the presence of antagonists...
February 8, 2018: Journal of Medicinal Food
Hao Zhou, Jin Wang, Pingjun Zhu, Shunying Hu, Jun Ren
Ripk3-mediated cellular apoptosis is a major contributor to the pathogenesis of myocardial ischemia reperfusion (IR) injury. However, the mechanisms by which Ripk3 influences microvascular homeostasis and endothelial apoptosis are not completely understood. In this study, loss of Ripk3 inhibited endothelial apoptosis, alleviated luminal swelling, maintained microvasculature patency, reduced the expression of adhesion molecules and limited the myocardial inflammatory response. In vitro, Ripk3 deficiency protected endothelial cells from apoptosis and migratory arrest induced by HR injury...
January 27, 2018: Cellular Signalling
Vishal R Yadav, Tengyao Song, Lin Mei, Leroy Joseph, Yun-Min Zheng, Yong-Xiao Wang
Hypoxia-induced pulmonary vasoconstriction (HPV) is attributed to an increase in intracellular Ca2+ concentration ([Ca2+]i) in pulmonary artery smooth muscle cells (PASMCs). We have reported that phospholipase C-γ1 (PLCγ1) plays a significant role in the hypoxia-induced increase in [Ca2+]i in PASMCs and attendant HPV. In this study, we intended to determine molecular mechanisms for hypoxic Ca2+ and contractile responses in PASMCs. Our data reveal that hypoxic vasoconstriction occurs in PAs, but not in mesenteric arteries (MAs)...
February 1, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Jun Li, Rui Zhou, Bei-Bei Bie, Na Huang, Ying Guo, Hai-Yan Chen, Meng-Jiao Shi, Jun Yang, Jian Zhang, Zong-Fang Li
AIM: To investigate the effects of combined use of emodin and baicalein (CEB) at the cellular and organism levels in severe acute pancreatitis (SAP) and explore the underlying mechanism. METHODS: SAP was induced by retrograde infusion of 5% sodium taurocholate into the pancreatic duct in 48 male SD rats. Pancreatic histopathology score, serum amylase activity, and levels of tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and IL-10 were determined to assess the effects of CEB at 12 h after the surgery...
January 7, 2018: World Journal of Gastroenterology: WJG
Tamara Vervloessem, Haidar Akl, Thomas Tousseyn, Humbert De Smedt, Jan B Parys, Geert Bultynck
Bcl-2 is often upregulated in cancers to neutralize the BH3-only protein Bim at the mitochondria. BH3 mimetics (e.g. ABT-199 (venetoclax)) kill cancer cells by targeting Bcl-2's hydrophobic cleft and disrupting Bcl-2/Bim complexes. Some cancers with elevated Bcl-2 display poor responses towards BH3 mimetics, suggesting an additional function for anti-apoptotic Bcl-2 in these cancers. Indeed, Bcl-2 via its BH4 domain prevents cytotoxic Ca2+ release from the endoplasmic reticulum (ER) by directly inhibiting the inositol 1,4,5-trisphosphate receptor (IP3R)...
December 19, 2017: Oncotarget
Adrien Nougarede, Nikolay Popgeorgiev, Loay Kassem, Soleilmane Omarjee, Stephane Borel, Ivan Mikaelian, Jonathan Lopez, Rudy Gadet, Olivier Marcillat, Isabelle Treilleux, Bruno O Villoutreix, Ruth Rimokh, Germain Gillet
Drug resistance and metastatic relapse remain a top challenge in breast cancer treatment. In this study, we present preclinical evidence for a strategy to eradicate advanced breast cancers by targeting the BCL2 homolog Nrh/BCL2L10, which we discovered to be overexpressed in >45% of a large cohort of breast invasive carcinomas. Nrh expression in these tumors correlated with reduced metastasis-free survival and we determined it to be an independent marker of poor prognosis. Nrh protein localized to the endoplasmic reticulum (ER)...
January 12, 2018: Cancer Research
Wei-Chun Xiao, Zhang Jing, Si-Li Chen, Yi-Jun Shi, Fan Xiao, Wei An
The aberrant release of Ca2+ from the endoplasmic reticulum (ER) contributes to the onset of ER stress, which is closely related to the pathogenesis of non-alcoholic fatty liver disease. We previously reported that augmenter of liver regeneration (ALR) alleviates ER stress and protects hepatocytes from lipotoxicity. However, the link between ALR protection and the suppression of ER stress remains unclear. In this study, we investigated whether the protection against liver steatosis afforded by ALR is related to its inhibition of calcium overflow from the ER to the mitochondria...
January 11, 2018: Journal of Cellular Physiology
Lin Li, Jiahui Cui, Zi Liu, Xuejiao Zhou, Zengqiang Li, Yang Yu, Yuanyuan Jia, Daiying Zuo, Yingliang Wu
Silver nanoparticles (AgNPs) have many medical and commercial applications, but their effects on human health are poorly understood. The aim of this study was to assess the effect of AgNPs on the human neuroblastoma cell line SH-SY5Y and to explore their potential mechanisms of action. We found that AgNPs decreased SH-SY5Y cell viability in a dose- and time-dependent manner. Exposure to AgNPs activated endoplasmic reticulum (ER) stress, as reflected by upregulated expression of glucose-regulated protein 78 (GRP78), phosphorylated PKR-like endoplasmic reticulum kinase (p-PERK), phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α), C/EBP homology protein (CHOP), spliced X-box binding protein-1 (XBP1), and phosphorylated inositol-requiring enzyme (p-IRE), all of which are involved in the cellular unfolded protein response...
January 3, 2018: Toxicology Letters
Hideaki Ando, Katsuhiro Kawaai, Benjamin Bonneau, Katsuhiko Mikoshiba
The calcium ion (Ca2+) is a ubiquitous intracellular signaling molecule that regulates diverse physiological and pathological processes, including cancer. Increasing evidence indicates that oncogenes and tumor suppressors regulate the Ca2+ transport systems. Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are IP3-activated Ca2+ release channels located on the endoplasmic reticulum (ER). They play pivotal roles in the regulation of cell death and survival by controlling Ca2+ transfer from the ER to mitochondria through mitochondria-associated ER membranes (MAMs)...
December 20, 2017: Advances in Biological Regulation
Xiuying Zhao, Yihan Xian, Chao Wang, Liren Ding, Xianglong Meng, Weiyun Zhu, Suqin Hang
This study aimed to understand the effect of Tryptophan (Trp) on gut hormones secretion as well as the roles of the CaSR and its downstream signaling pathway in gut hormones secretion using swine duodenal perfusion in vitro. Swine duodenum was perfused with Krebs-Henseleit buffers (KHB) as a basal solution. Various concentrations (0, 10 mM and 20 mM) of Trp were applied to investigate the effect of Trp on gut hormones secretion. A CaSR antagonist was used to detect the involvement of CaSR and its signal molecules...
December 28, 2017: Journal of Veterinary Science
Qing Song, Wen-Li Gou, Yu-Liang Zou
BACKGROUND/AIMS: Stroke is the leading cause of adult disability, and glutamate-induced dysregulation of intracellular Ca2+ homeostasis is a key mechanism. FAM3A is the first member of the family with sequence similarity 3 (FAM3) gene family, and its biological function remains largely unknown. We have recently reported that FAM3A exerts protective effects against oxidative stress and mitochondrial dysfunction in HT22 cells. METHODS: Here, we investigated the protective effects of FAM3A using a glutamate-induced neuronal injury model in nerve growth factor (NGF)-differentiated PC12 cells...
December 12, 2017: Cellular Physiology and Biochemistry
Qi Xie, Ye Xu, Weinan Gao, Yong Zhang, Jing Su, Yanan Liu, Yuting Guo, Minghan Dou, Kebang Hu, Liankun Sun
Ovarian cancer is the most common gynecological malignancy. At present, cisplatin is used to treat ovarian cancer; however, the development of cisplatin resistance during therapy is a common obstacle to achieving favorable outcomes. Recently, the B‑cell lymphoma 2 (Bcl‑2) BH4 domain has been reported to mediate the prosurvival activity of Bcl‑2 in cancer; however, the involvement of the BH4 domain of Bcl‑2 in the cisplatin resistance of ovarian carcinoma cells is not entirely clear. In this study, we observed the cytoplasmic and mitochondrial levels of Ca2+ by confocal laser microscopy...
February 2018: International Journal of Molecular Medicine
Yan Wang, Liu Tu, Yingbo Li, Di Chen, Zhao Liu, Xuelian Hu, Shali Wang
As documented in our previous study, notoginsenoside R1 (NGR1) can inhibit neuron apoptosis and the expression of endoplasmic reticulum (ER) stress-associated pro-apoptotic proteins in hypoxic-ischemic encephalopathy. Recent evidence indicates that the Phospholipase C (PLC)/inositol 1,4,5-trisphosphate receptor (IP3R) is important for the regulation of Ca2+ release in the ER. Ca2+ imbalance can stimulate ER stress, CAMKII, and cell apoptosis. The purpose of this study was to further investigate the neuroprotective effect of NGR1 and elucidate how NGR1 regulates ER stress and cell apoptosis in the oxygen-glucose deprivation/reoxygenation (OGD/R) model...
November 24, 2017: Scientific Reports
Michelle Flores Domingues, Dênis Reis de Assis, Angela Regina Piovesan, Cháriston André Dal Belo, Jaderson Costa da Costa
Peptide YY (PYY) belongs to the neuropeptide Y (NPY) family, which also includes the pancreatic polypeptide (PP) and NPY. PYY is secreted by the intestinal L cells, being present in the blood stream in two active forms capable of crossing the blood brain barrier, PYY (1-36) and its cleavage product, PYY (3-36). PYY is a selective agonist for the Y2 receptor (Y2R) and these receptors are abundant in the hippocampus. Here we investigated the mechanisms by which PYY (3-36) regulates intracellular Ca(2+) concentrations ([Ca(2+)]i) in hippocampal neurons by employing a calcium imaging technique in hippocampal cultures...
November 7, 2017: Neuropeptides
Nagendra Babu Thillaiappan, Alap P Chavda, Stephen C Tovey, David L Prole, Colin W Taylor
IP3 receptors (IP3 Rs) release Ca2+ from the ER when they bind IP3 and Ca2+ . The spatial organization of IP3 Rs determines both the propagation of Ca2+ signals between IP3 Rs and the selective regulation of cellular responses. Here we use gene editing to fluorescently tag endogenous IP3 Rs, and super-resolution microscopy to determine the geography of IP3 Rs and Ca2+ signals within living cells. We show that native IP3 Rs cluster within ER membranes. Most IP3 R clusters are mobile, moved by diffusion and microtubule motors...
November 15, 2017: Nature Communications
Yong-Bo Li, Xu-Yang Pei, Di Wang, Cai-Hua Chen, Mei-Juan Cai, Jin-Xing Wang, Xiao-Fan Zhao
Animal steroid hormones stimulate extracellular Ca(2+) influx into cells; however, the mechanism remains unclear. In this study, we determined that the Ca(2+) influx induced by steroid hormone 20-hydroxyecdysone (20E) is mediated by the calcium release-activated calcium channel modulator 1 (CRACM1/Orai1). The Orai1 mRNA is highly expressed during midgut programmed cell death in the lepidopteran insect Helicoverpa armigera. 20E upregulated the expression of Orai1 in H. armigera larvae and in an epidermal cell line (HaEpi)...
December 2017: Cell Calcium
Nino Goguadze, Elene Zhuravliova, Didier Morin, Davit Mikeladze, Tangui Maurice
The sigma1 receptor (σ1R) is a chaperone protein residing at mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), where it modulates Ca(2+) exchange between the ER and mitochondria by interacting with inositol-1,4,5 trisphosphate receptors (IP3Rs). The σ1R is highly expressed in the central nervous system and its activation stimulates neuromodulation and neuroprotection, for instance in Alzheimer's disease (AD) models in vitro and in vivo. σ1R effects on mitochondria pathophysiology and the downstream signaling are still not fully understood...
November 10, 2017: Neurotoxicity Research
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