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Muna Suleiman, Nabeel Abdulrahman, Huseyin Yalcin, Fatima Mraiche
Cardiac remodeling, characterized by excessive extracellular matrix (ECM) remodeling, predisposes the heart to failure if left unresolved. Understanding the signaling mechanisms involved in excessive extracellular matrix (ECM) remodeling is necessary to identify the means to regress the development of cardiac remodeling and heart failure. Recently, hyaluronan (HA), a ubiquitously expressed glycosaminoglycan in the ECM, was shown to participate in tissue fibrosis and myofibroblast proliferation through interacting with its ubiquitously expressed cell-surface receptor, CD44...
August 5, 2018: Life Sciences
Rittwika Bhattacharya, Chinmay Kumar Panda, Sourav Nandi, Ashis Mukhopadhyay
Mechanical or fostered molecular events define metastatic cascade. Three distinct sets of molecular events characterize metastasis, viz invasion of extracellular matrix; angiogenesis, vascular dissemination and anoikis resistance; tumor homing and relocation of tumor cells to selective organ. Invasion of extracellular matrix requires epithelial to mesenchymal transition through disrupted lamellopodia formation and contraction of actin cytoskeleton; aberration of Focal adhesion complex formation involving integrins and the extracellular matrix; degradation of extracellular matrix by matrix metalloproteases; faulty immune surveillance in tumor microenvironment and an upregulated proton efflux pump NHE1 in tumors...
August 2018: Pathology, Research and Practice
Debajyoti Dutta, Larry Fliegel
Na+/H+ exchanger isoform one (NHE1) is a mammalian plasma membrane protein that removes intracellular protons, thereby elevating intracellular pH (pHi). NHE1 uses the energy of allowing an extracellular sodium down its gradient into cells, to remove 1 intracellular proton. The ubiquitous protein has several important physiological and pathological influences on mammalian cells as a result of its activity. The three dimensional structure of human NHE1 (hNHE1) is not known. Here, we modeled NHE1 based on the structure of MjNhaP1 of Methanocaldoccocus jannaschii in combination with biochemical surface accessibility data...
July 30, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
Harry C Blair, Quitterie C Larrouture, Irina L Tourkova, Li Liu, Jing Hao Bian, Donna Beer Stolz, Deborah J Nelson, Paul H Schlesinger
Osteoblasts secrete collagen and isolate bone-matrix from extracellular space. In the matrix, alkaline phosphatase generates phosphate that combines with calcium to form mineral, liberating 8 H+ per 10 Ca+2 deposited. However, pH- dependent hydroxyapatite deposition on bone collagen had not been shown. We studied dependency of hydroxyapatite deposition on type I collagen on pH and phosphate by surface plasmon resonance in 0-5 mM phosphate at pH 6.9-7.6. Mineral deposition saturated at <1 mM Ca2+ , but was sensitive to phosphate...
July 25, 2018: American Journal of Physiology. Cell Physiology
Shanshan Song, Shaoxia Wang, Victoria M Pigott, Tong Jiang, Lesley M Foley, Abhishek Mishra, Rachana Nayak, Wen Zhu, Gulnaz Begum, Yejie Shi, Karen E Carney, T Kevin Hitchens, Gary E Shull, Dandan Sun
Na+ /H+ exchanger (NHE1) activation is required for multiple microglial functions. We investigated effects of selective deletion of microglial Nhe1 in Cx3cr1-CreER ;Nhe1f/f mice on neuroinflammation and tissue repair after ischemic stroke. Infarct volume was similar in corn oil or tamoxifen (Tam)-treated mice at 48 hr and 14 days post-stroke. However, the Tam-treated mice showed significantly higher survival rate and faster neurological function recovery during day 1-14 post-stroke. Deletion of microglial Nhe1 prevented the elevation of CD11b+ /CD45low-med microglia in the ischemic hemisphere at day 3 post-stroke, but stimulated expression of Ym1, CD68, TGF-β, IL-10, decreased expression of CD86 and IL-1β, and reduced GFAP+ reactive astrocytes...
July 25, 2018: Glia
Peng Wang, Xin Wang, Ling Li, Quancheng Kan, Zujiang Yu, Rongfang Feng, ZiXiao Chen, Yan Shi, Jinling Gao
BACKGROUND: The "secondary injury" theory of liver failure indicated that hyperammonaemia due to liver failure causes further deterioration of hepatocytes. Our previous studies have demonstrated that high blood ammonia levels may lead to hepatocyte apoptosis, as NH4 Cl loading caused metabolic acidosis and an increase in sodium-hydrogen exchanger isoform 1 (NHE1). In this study, we established a hyperammonia hepatocyte model to determine the role of NHE1 in the regulation of hepatocyte apoptosis induced by NH4 Cl...
July 19, 2018: Gastroenterología y Hepatología
Jin Xue, Dan Zhou, Orit Poulsen, Iain Hartley, Toshihiro Imamura, Edward X Xie, Gabriel G Haddad
Numerous studies have demonstrated that Na+ /H+ exchanger isoform 1 (NHE1) is elevated in myocardial diseases and its effect is detrimental. To better understand the involvement of NHE1, we have previously studied cardiac-specific NHE1 transgenic mice and shown that these mice develop cardiac hypertrophy, interstitial fibrosis and cardiac dysfunction. The purpose of current study was to identify microRNAs and their mRNA targets involved in NHE1-mediated cardiac injury. An un-biased high throughput sequencing study was performed on both microRNAs and mRNAs...
July 20, 2018: Physiological Genomics
Kazuhiro Iwama, Hitoshi Osaka, Takahiro Ikeda, Satomi Mitsuhashi, Satoko Miyatake, Atsushi Takata, Noriko Miyake, Shuichi Ito, Takeshi Mizuguchi, Naomichi Matsumoto
The mammalian Na+ /H+ exchanger isoform one (NHE1), encoded by Solute Carrier Family 9, member 1 (SLC9A1), consists of 12 membrane domains and a cytosolic C-terminal domain. NHE1 plays an important role in maintaining intracellular pH homeostasis by exchanging one intracellular proton for one extracellular sodium ion. Mice with a homozygous null mutation in Slc9a1 (Nhe1) exhibited ataxia, recurrent seizures, and selective neuronal cell death. In humans, three unrelated patients have been reported: a patient with a homozygous missense mutation in SLC9A1, c...
July 17, 2018: Journal of Human Genetics
Vanessa Gerolde Cardoso, Guilherme Lopes Gonçalves, Juliana Martins Costa-Pessoa, Karina Thieme, Bruna Bezerra Lins, Fernando Augusto Malavazzi Casare, Mariana Charleaux de Ponte, Niels Olsen Saraiva Camara, Maria Oliveira-Souza
BACKGROUND: Angiotensin II (Ang II) contributes to the progression of renal diseases associated with proteinuria and glomerulosclerosis mainly by inducing podocyte apoptosis. In the present study, we investigated whether the chronic effects of Ang II via AT1 receptor (AT1R) would result in endoplasmic reticulum (ER) stress/PKC-delta/p38 MAPK stimulation, and consequently podocyte apoptosis. METHODS: Wistar rats were treated with Ang II (200 ng·kg-1 ·min-1 , 42 days) and or losartan (10 mg·kg-1 ·day-1 , 14 days)...
July 13, 2018: BMC Nephrology
Shiao-Pieng Lee, Shih-Chi Chao, Shu-Fu Huang, Yen-Lin Chen, Yi-Ting Tsai, Shih-Hurng Loh
BACKGROUND/AIMS: To functionally characterize intracellular pH (pHi) regulating mechanisms, such as Na+-H+ exchanger (NHE) and Na+-HCO3- co-transporter (NBC), and further examine effects of ethanol on the pHi regulating mechanism in human oral epidermoid carcinoma (OEC-M1) cells. METHODS: OEC-M1 cells were a gift from Tri-Service General Hospital. Changes of pHi were detected by microspectrofluroimetry with a pH-sensitive fluorescent dye, BCECF. Isoforms of transporters were examined by Western blot technique...
2018: Cellular Physiology and Biochemistry
Xiaohui Zhao, Tian Xie, Ting Dai, Wenhui Zhao, Jing Li, Rui Xu, Chao Jiang, Peiqiong Li, Junyao Deng, Xiaobo Su, Ningfang Ma
Calcineurin B homologous protein isoform 2 (CHP2), an essential cofactor for Na+/H+ exchanger isoform 1 (NHE1), is identified to be expressed in various malignant cell lines. However, the clinical significance and biological role of CHP2 in breast cancer remain to be established. Here, CHP2 was markedly overexpressed in breast cancer cells and clinical tumor specimens. Immunohistochemical (IHC) analysis revealed that the expression of CHP2 was significantly correlated with patients' clinicopathologic characteristics like clinical stage, and breast cancer patients with high CHP2 expression had shorter overall survival compared to patients with low CHP2 expression...
July 2, 2018: Molecular Cancer Research: MCR
Yen-Cheng Chen, Chung-Yi Cheng, Chung-Te Liu, Yuh-Mou Sue, Tso-Hsiao Chen, Yung-Ho Hsu, Pai-An Hwang, Cheng-Hsien Chen
ETHNOPHARMACOLOGICAL RELEVANCE: Brown seaweed is a common food for Asians, and the bioactive ingredient fucoxanthin exerts anti-apoptotic activities in several cell types. Renal tubular cell apoptosis is one of the common cellular events leading to renal fibrosis and chronic kidney disease (CKD). However, the influence of fucoxanthin-containing brown seaweed extract on CKD is still unknown. We intended to evaluate the inhibitory effect of fucoxanthin-containing extract from brown seaweed on renal apoptosis under CKD condition and its molecular mechanism...
October 5, 2018: Journal of Ethnopharmacology
Mette Flinck, Signe Hoejland Kramer, Julie Schnipper, Anne Poder Andersen, Stine Falsig Pedersen
Precise acid-base homeostasis is essential for maintaining normal cell proliferation and growth. Conversely, dysregulated acid-base homeostasis, with increased acid extrusion and marked extracellular acidification, is an enabling feature of solid tumors, yet the mechanisms through which intra- and extracellular pH (pHi , pHe ) impact proliferation and growth are incompletely understood. The aim of this study was to determine the impact of pH, and specifically of the Na+ /H+ exchanger NHE1 and Na+ , HCO3 - transporter NBCn1, on cell cycle progression and its regulators in human breast cancer cells...
July 13, 2018: Cell Cycle
Huilong Luo, Matthieu Gauthier, Xi Tan, Christophe Landry, Joël Poupon, Marie-Pierre Dehouck, Fabien Gosselet, Nicolas Perrière, Frank Bellivier, Salvatore Cisternino, Xavier Declèves
Variability in drug response to lithium (Li+ ) is poorly understood and significant, as only 40% of patients with bipolar disorder highly respond to Li+ . Li+ can be transported by sodium (Na+ ) transporters in kidney tubules or red blood cells, but its transport has not been investigated at the blood-brain barrier (BBB). Inhibition and/or transcriptomic strategies for Na+ transporters such as NHE (SLC9), NBC (SLC4), and NKCC (SLC12) were used to assess their role on Li+ transport in human brain endothelial cells...
July 2, 2018: Molecular Pharmaceutics
Ehrhardt Proksch
The pH plays an important physiological role in nature and humans. pH varies from 1 to 8 in human organs with tight regulation in blood and epithelia of barrier organs. The physiological pH of the stratum corneum is 4.1-5.8 and several mechanisms contribute to its formation: filaggrin degradation, fatty acid content, sodium-hydrogen exchanger (NHE1) activation and melanosome release. First, the acidic pH of the stratum corneum was considered to present an antimicrobial barrier preventing colonization (e.g. by Staphylococcus aureus and Malassezia)...
June 4, 2018: Journal of Dermatology
A Koch, A Schwab
Melanoma incidence is on the rise and currently causes the majority of skin cancer-related deaths. Yet, therapies for metastatic melanoma are still insufficient so that new concepts are essential. Malignant transformation of melanocytes and melanoma progression are intimately linked to the cutaneous pH landscape and its dysregulation in tumour lesions. The pH landscape of normal skin is characterized by a large pH gradient of up to 3 pH units between surface and dermis. The Na+ /H+ exchanger NHE1 is one of the major contributors of acidity in superficial skin layers...
May 26, 2018: Acta Physiologica
Jianling Li, Qiaoling He, Qingjie Li, Rongjie Huang, Xiaoyan Wei, Xiaofeng Pan, Weifeng Wu
To determine whether the sympathetic nerve plays a role in the regulation of Na+ -H+ exchange (NHE) in the kidney of spontaneously hypertensive rats (SHR), we investigated the expression of NHE and NHE regulatory protein family (NHERF) in the denervated kidneys compared with intact kidneys. Twelve-week-old male SHR and age-matched Wistar Kyoto (WKY) rats were used. SHR were randomly assigned to the renal denervated (RDNX, n = 8) or Sham (n = 8) groups. The protein and mRNA expression of NHE1, NHE3, NHERF1 and NHERF2 were assessed in the kidney of the groups...
May 22, 2018: Clinical and Experimental Hypertension: CHE
John C Huetsch, Jasmine Walker, Clark Undem, Julie Lade, Xin Yun, Syeda Baksh, Haiyang Jiang, Ning Lai, Larissa A Shimoda
Excessive production of endothelin-1 (ET-1) has been observed in almost all forms of pulmonary hypertension. ET-1, a highly potent vasoconstrictor, can also potentiate pulmonary arterial smooth muscle cell (PASMC) growth and migration, both of which contribute to the vascular remodeling that occurs during the development of pulmonary hypertension. Increasing evidence indicates that alkalinization of intracellular pH (pHi ), typically due to activation of Na+ /H+ exchange (NHE), is associated with enhanced PASMC proliferation and migration...
May 2018: Physiological Reports
Mohammed Albatany, Alex Li, Susan Meakin, Robert Bartha
Glioblastoma is an aggressive brain cancer that is very difficult to treat. Clinically, it is important to be able to distinguish aggressive from non-aggressive brain tumors. Previous studies have shown that some drugs can induce a rapid change in intracellular pH that could help to identify aggressive cancer. The sodium proton exchanger (NHE1) plays a significant role in maintaining pH balance in the tumor microenvironment. Cariporide is a sodium proton exchange inhibitor that is well tolerated by humans in cardiac applications...
May 10, 2018: International Journal of Clinical Oncology
Deise C A Leite-Dellova, Shirley J Szriber, Giovana K F Merighe, Juliano Z Polidoro, Nancy A Rebouças, Maria Oliveira-Souza, Margarida de Mello-Aires
The receptors and signaling pathways for nongenomic effects of aldosterone (Aldo) on the proximal Na+ /H+ exchanger are still unknown; therefore, the aim of this study was to investigate the mineralocorticoid receptor (MR) and/or glucocorticoid receptor (GR) participation in rapid Aldo effects on NHE1 (basolateral Na+ /H+ exchanger isoform) and cytosolic calcium concentration ([Ca2+ ]i ). In addition, phospholipase C (PLC), protein kinase C (PKC), and mitogen-activated protein kinase kinase (MEK) involvement in signaling pathways of such effects was evaluated, using immortalized proximal tubule cells of rat (IRPTC) as an experimental model...
September 2018: Journal of Steroid Biochemistry and Molecular Biology
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