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pH homeostasis

Sylvie Breton, Dennis Brown
BACKGROUND: Serious and often fatal acute kidney injury (AKI) is frequently seen after major surgery, local and remote organ damage, and sepsis. It is associated with uncontrolled inflammation, and is usually diagnosed only after the kidneys have gone through significant and often irreversible damage. SUMMARY: During our work involving another type of kidney disease that leads to acid-base disorders of the blood, we unexpectedly found high levels of a protein called the P2Y14 "purinergic" receptor, in specialized kidney epithelial cells called intercalated cells (ICs)...
2018: Annals of Nutrition & Metabolism
Soojung Lee, Trine V Axelsen, Nicolai Jessen, Stine F Pedersen, Pernille Vahl, Ebbe Boedtkjer
Metabolic acid production challenges cellular pH homeostasis in solid cancer tissue, and mechanisms of net acid extrusion represent promising new targets for breast cancer therapy. Here, we used genetically engineered mice to investigate the contribution of the Na+ ,HCO3 - -cotransporter NBCn1 (Slc4a7) to intracellular acid-base regulation in ErbB2-induced breast cancer tissue and the consequences of NBCn1 knockout for breast tumor development and growth. We demonstrate an approximately 2-fold increase of NBCn1 protein abundance in ErbB2-induced breast cancer tissue compared to normal breast tissue despite a 4-fold decrease in the NBCn1 mRNA level...
June 15, 2018: Oncogene
Alice Biosa, Irene Arduini, Maria Eugenia Soriano, Valentina Giorgio, Paolo Bernardi, Marco Bisaglia, Luigi Bubacco
The preferential degeneration of dopaminergic neurons in the substantia nigra pars compacta is responsible for the motor impairment associated with Parkinson's disease. Dopamine is a highly reactive molecule, which is usually stored inside synaptic vesicles where it is stabilized by the ambient low pH. However, free cytosolic dopamine can auto-oxidize, generating reactive oxygen species, and lead to the formation of toxic quinones. In the present work, we have analyzed the mechanisms through which the dysfunction of dopamine homeostasis could induce cell toxicity, by focusing in particular on the damage induced by dopamine oxidation products at the mitochondrial level...
June 15, 2018: ACS Chemical Neuroscience
Katie E Marshall, Brent J Sinclair
Internal ice formation leads to wholesale changes in ionic, osmotic and pH homeostasis, energy metabolism, and mechanical damage, across a small range of temperatures, and is thus an abiotic stressor that acts at a distinct, physiologically-relevant, threshold. Insects that experience repeated freeze-thaw cycles over winter will cross this stressor threshold many times over their lifespan. Here we examine the effect of repeatedly crossing the freezing threshold on short-term physiological parameters (metabolic reserves and cryoprotectant concentration) as well as long-term fitness-related performance (survival and egg production) in the freeze-tolerant goldenrod gall fly Eurosta solidaginis We exposed overwintering prepupae to a series of low temperatures (-10, -15, or -20 °C) with increasing numbers of freezing events (3, 6, or 10) with differing recovery periods between events (1, 5, or 10 days)...
June 12, 2018: Journal of Experimental Biology
Mette Flinck, Signe Hoejland Kramer, Julie Schnipper, Anne P Andersen, Stine F 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...
June 12, 2018: Cell Cycle
Tessa R Young, Tara L Pukala, Roberto Cappai, Anthony G Wedd, Zhiguang Xiao
A manifestation of Alzheimer's disease (AD) is the aggregation in the brain of Aβ peptides derived from the amyloid precursor protein (APP). APP has been linked to modulation of normal copper homeostasis while dysregulation of Aβ production and clearance has been associated with disruption of copper balance. However, quantitative copper chemistry on APP is lacking, in contrast to the plethora of copper chemistry available for Aβ peptides. The soluble extracellular protein domain sAPPα (molar mass including post-translational modifications ~ 100 kD) has now been isolated in good yield and high quality...
June 12, 2018: Biochemistry
Adelaide S M Dennis, James E O Rosling, Adele M Lehane, Kiaran Kirk
Four hundred structurally diverse drug-like compounds comprising the Medicines for Malaria Venture's 'Pathogen Box' were screened for their effect on a range of physiological parameters in asexual blood-stage malaria (Plasmodium falciparum) parasites. Eleven of these compounds were found to perturb parasite Na+ , pH and volume in a manner consistent with inhibition of the putative Na+ efflux P-type ATPase PfATP4. All eleven compounds fell within the subset of 125 compounds included in the Pathogen Box on the basis of their having been identified as potent inhibitors of the growth of asexual blood-stage P...
June 11, 2018: Scientific Reports
Sevil Köse, Nilgün Yersal, Selin Önen, Petek Korkusuz
Recent advances require a dual evaluation of germ and somatic stem cell niches with a regenerative medicine perspective. For a better point of view of the niche concept, it is needed to compare the microenvironments of those niches in respect to several components. The cellular environment of spermatogonial stem cells' niche consists of Sertoli cells, Leydig cells, vascular endothelial cells, epididymal fat cells, peritubular myoid cells while hematopoietic stem cells have mesenchymal stem cells, osteoblasts, osteoclasts, megacaryocytes, macrophages, vascular endothelial cells, pericytes and adipocytes in their microenvironment...
June 8, 2018: Advances in Experimental Medicine and Biology
Aravindakshan Ajith Kumar, Nadimpalli Siva Kumar
Acidic α-mannosidase is an important enzyme and is reported from many different plants and animals. Lysosomal α-mannosidase helps in the catabolism of glycoproteins in the lysosomes thereby playing a major role in cellular homeostasis. In the present study lysosomal α-mannosidase from the gonads of echinoderm Asterias rubens was isolated and purified. The crude protein sample from ammonium sulfate precipitate contained two isoforms of mannosidase as tested by the MAN2B1 antibody, which were separated by anion exchange chromatography...
June 7, 2018: Protein Journal
María E Solesio, Pablo M Peixoto, Ludovic Debure, Stephen M Madamba, Mony J de Leon, Thomas Wisniewski, Evgeny V Pavlov, Silvia Fossati
Mounting evidence suggests that mitochondrial dysfunction plays a causal role in the etiology and progression of Alzheimer's disease (AD). We recently showed that the carbonic anhydrase inhibitor (CAI) methazolamide (MTZ) prevents amyloid β (Aβ)-mediated onset of apoptosis in the mouse brain. In this study, we used MTZ and, for the first time, the analog CAI acetazolamide (ATZ) in neuronal and cerebral vascular cells challenged with Aβ, to clarify their protective effects and mitochondrial molecular mechanism of action...
June 5, 2018: Aging Cell
Alexandre Martinière, Rémy Gibrat, Hervé Sentenac, Xavier Dumont, Isabelle Gaillard, Nadine Paris
Building a proton gradient across a biological membrane and between different tissues is a matter of great importance for plant development and nutrition. To gain a better understanding of proton distribution in the plant root apoplast as well as across the plasma membrane, we generated Arabidopsis plants expressing stable membrane-anchored ratiometric fluorescent sensors based on pHluorin. These sensors enabled noninvasive pH-specific measurements in mature root cells from the medium-epidermis interface up to the inner cell layers that lie beyond the Casparian strip...
June 4, 2018: Proceedings of the National Academy of Sciences of the United States of America
N C N Perera, G I Godahewa, Bo-Hye Nam, Jung Youn Park, Jehee Lee
Disturbance in the balance between pro-oxidants and anti-oxidants result oxidative stress in aerobic organisms. However, oxidative stress can be inhibited by enzymatic and non-enzymatic defense mechanisms. Superoxide dismutases (SODs) are well-known scavengers of superoxide radicals, and they protect cells by detoxifying hazardous reactive oxygen species. Here, we have identified and characterized two different SODs, CuZnSOD and MnSOD, from black rockfish (RfCuZnSOD and RfMnSOD, respectively). In silico analysis revealed the well-conserved molecular structures comprising all essential properties of CuZnSOD and MnSOD...
May 30, 2018: Fish & Shellfish Immunology
Tomaz Crochemore, Felicio A Savioli
BACKGROUND: Hemorrhagic shock is a medical emergency that often complicates vascular surgery and can lead to death. Hemorrhagic shock is characterized by hypoperfusion and hemodynamic abnormalities leading to the collapse of homeostasis due to massive blood loss. Early diagnosis is critical for a favorable outcome. Thromboelastometry has been considered an effective tool for bleeding management in critically ill patients. Thromboelastometry can guide transfusion therapy quickly, reducing the need for blood products...
June 2, 2018: Journal of Medical Case Reports
Manish Kumar Jain, Priyanka Singh, Sneha Roy, Rajiv Bhat
The human synucleins family is comprised of α-, β- and γ-syn proteins. α-syn has the highest propensity for aggregation, and its aggregated forms accumulate in Lewy bodies (LB) and Lewy neuritis (LN), which are involved in Parkinson's disease (PD). β- and γ-syn are absent in LB and their exact role is still enigmatic. β-syn does not form aggregates under physiological conditions (pH 7.4), while γ-syn is associated with neural and non-neural diseases like breast cancer. Due to their similar regional distribution in brain, natively unfolded structure and high sequence homology, it has become important to study the effect of environment on their conformation, interactions, fibrillation and fibril morphologies...
May 31, 2018: Biochemistry
John A Sargent, Marco Marano, Stefano Marano, F John Gennari
In patients receiving hemodialysis, it has long been recognized that much more bicarbonate is delivered during treatment than ultimately appears in the blood. To gain insight into this mystery, we developed a model that allows a quantitative analysis of the patient's response to rapid alkalinization during hemodialysis. Our model is unique in that it is based on the distribution of bicarbonate in the extracellular fluid and assesses its removal from this compartment by mobilization of protons (H+ ) from buffers and other sources...
May 29, 2018: Seminars in Dialysis
Jun Peng, Jingwei Yu, Hu Xu, Chen Kang, Philip W Shaul, Youfei Guan, Xiaoyan Zhang, Wen Su
BACKGROUND/AIMS: Transient lipid accumulation within hepatocytes preceding the peak proliferative process is a characteristic feature of liver regeneration. However, molecular mediators responsible for this lipid accumulation and their functions are not well defined. Sterol regulatory element-binding proteins-1c (SREBP-1c) are critical transcriptional factors that regulate lipid homeostasis in the liver. We hypothesized that SREBP-1c deficiency induced alterations of lipid metabolism may influence hepatocyte proliferation and liver regeneration...
May 22, 2018: Cellular Physiology and Biochemistry
Andrew P Holmes, Clare J Ray, Emma L Thompson, Ziyad Alshehri, Andrew M Coney, Prem Kumar
Ventilatory and neuroendocrine counter-regulatory responses during hypoglycaemia are essential in order to maintain glycolysis and prevent rises in Pa CO2 leading to systemic acidosis. The mammalian carotid body has emerged as an important driver of hyperpnoea and glucoregulation in hypoglycaemia. However, the adequate stimulus for CB stimulation in hypoglycaemia has remained controversial for over a decade. The recent finding that adrenaline is a physiological activator of CB in hypoglycaemia raises the intriguing possibility that CB stimulation and hyperpnoea may be necessary to maintain pH in other adrenaline-related hypermetabolic states such as exercise...
May 25, 2018: Respiratory Physiology & Neurobiology
Reza Zolfaghari Emameh, Harlan R Barker, Vesa P Hytönen, Seppo Parkkila
Genomic islands (GIs) are a type of mobile genetic element (MGE) that are present in bacterial chromosomes. They consist of a cluster of genes which produce proteins that contribute to a variety of functions, including, but not limited to, regulation of cell metabolism, anti-microbial resistance, pathogenicity, virulence, and resistance to heavy metals. The genes carried in MGEs can be used as a trait reservoir in times of adversity. Transfer of genes using MGEs, occurring outside of reproduction, is called horizontal gene transfer (HGT)...
May 25, 2018: Applied and Environmental Microbiology
Wenwen Wang, Jiayi He, Daodong Pan, Zhen Wu, Yuxing Guo, Xiaoqun Zeng, Liwei Lian
The adhesion ability of Lactobacillus plantarum affects retention time in the human gastro-intestinal tract, as well as influencing the interaction with their host. In this study, the relationship between the adhesion activity of, and metabolic changes in, L. plantarum ATCC 14917 under initial acid and alkali stress was evaluated by analyzing auto-aggregation, protein adhesion and cell adhesion in vitro. Based on scanning electron microscope (SEM) and transmission electron microscope (TEM) analysis, the morphology of the bacteria became thickset and the thickness of their cell walls decreased under initial alkali stress...
2018: PloS One
Jian Xu, Jingjing Wang, Mengyu He, Honghao Han, Weiping Xie, Hong Wang, Hui Kong
Dipeptidyl peptidase IV (DPP-4) is well known for its role in glucose homeostasis, and DPP-4 inhibitor (DPP-4i) exhibits multiple actions in cardiovascular diseases. However, the effect of DPP-4i on pulmonary hypertension (PH) remains unclear. Therefore, this study aims to investigate the effect of DPP-4i on pulmonary arterial remodeling in rats with PH and the potential underlying mechanisms. Our results show that DPP-4 was expressed in epithelial cells, endothelial cells, smooth muscle cells, and inflammatory cells in lung...
May 22, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
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