Chronic continuous hypoxia decreases the expression of SLC4A7 (NBCn1) and SLC4A10 (NCBE) in mouse brain

2007 ◽  
Vol 293 (6) ◽  
pp. R2412-R2420 ◽  
Author(s):  
Li-Ming Chen ◽  
Inyeong Choi ◽  
Gabriel G. Haddad ◽  
Walter F. Boron
Keyword(s):  
Mouse Brain ◽  
Chronic Hypoxia ◽  
Ph Regulation ◽  
Protein Abundance ◽  
Ph Homeostasis ◽  
Acid Base ◽  
Protein Levels ◽  
Stage Of Development ◽  
Wide Range ◽  
The Central Nervous System

In the mammalian CNS, hypoxia causes a wide range of physiological effects, and these effects often depend on the stage of development. Among the effects are alterations in pH homeostasis. Na+-coupled HCO3− transporters can play critical roles in intracellular pH regulation and several, such as NCBE and NBCn1, are expressed abundantly in the central nervous system. In the present study, we examined the effect of chronic continuous hypoxia on the expression of two electroneutral Na-coupled HCO3− transporters, SLC4a7 (NBCn1) and SLC4a10 (NCBE), in mouse brain, the first such study on any acid-base transporter. We placed the mice in normobaric chambers and either maintained normoxia (21% inspired O2) or imposed continuous chronic hypoxia (11% O2) for a duration of either 14 days or 28 days, starting from ages of either postnatal age 2 days (P2) or P90. We assessed protein abundance by Western blot analysis, loading equal amounts of total protein for each condition. In most cases, hypoxia reduced NBCn1 levels by 20–50%, and NCBE levels by 15–40% in cerebral cortex, subcortex, cerebellum, and hippocampus, both after 14 and 28 days, and in both pups and adults. We hypothesize that these decreases, which are out of proportion to the expected overall decreases in brain protein levels, may especially be important for reducing energy consumption.

scholarly journals Extracellular Acid-Base Balance and Ion Transport Between Body Fluid Compartments

Physiology ◽  
2017 ◽  
Vol 32 (5) ◽  
pp. 367-379 ◽  
Author(s):  
Julian L. Seifter ◽  
Hsin-Yun Chang
Keyword(s):  
Ion Transport ◽  
Ph Regulation ◽  
Extracellular Fluid ◽  
Transport Processes ◽  
Electrolyte Balance ◽  
Ph Homeostasis ◽  
Acid Base Balance ◽  
Acid Base ◽  
Base Balance ◽  
Fluid Compartments

Clinical assessment of acid-base disorders depends on measurements made in the blood, part of the extracellular compartment. Yet much of the metabolic importance of these disorders concerns intracellular events. Intracellular and interstitial compartment acid-base balance is complex and heterogeneous. This review considers the determinants of the extracellular fluid pH related to the ion transport processes at the interface of cells and the interstitial fluid, and between epithelial cells lining the transcellular contents of the gastrointestinal and urinary tracts that open to the external environment. The generation of acid-base disorders and the associated disruption of electrolyte balance are considered in the context of these membrane transporters. This review suggests a process of internal and external balance for pH regulation, similar to that of potassium. The role of secretory gastrointestinal epithelia and renal epithelia with respect to normal pH homeostasis and clinical disorders are considered. Electroneutrality of electrolytes in the ECF is discussed in the context of reciprocal changes in Cl−or non Cl−anions and [Formula: see text].

scholarly journals Elucidating the acid-base mechanisms underlying otolith overgrowth in fish exposed to ocean acidification

2021 ◽  
Author(s):  
Garfield Tsz Kwan ◽  
Martin Tresguerres
Keyword(s):  
Ocean Acidification ◽  
Inner Ear ◽  
Direct Evidence ◽  
Ph Regulation ◽  
Regulatory Mechanisms ◽  
Protein Abundance ◽  
Acid Base ◽  
Exposed Fish ◽  
Ph Buffering ◽  
Multiple Species

Over a decade ago, ocean acidification (OA) exposure was reported to induce otolith overgrowth in teleost fish. This phenomenon was subsequently confirmed in multiple species; however, the underlying physiological causes remain unknown. Here, we report that splitnose rockfish (Sebastes diploproa) exposed to ~1,600 μatm pCO2 (pH ~7.5) were able to fully regulated the pH of both blood and endolymph (the fluid that surrounds the otolith within the inner ear). However, while blood was regulated around pH 7.80, the endolymph was regulated around pH ~8.30. These different pH setpoints result in increased pCO2 diffusion into the endolymph, which in turn leads to proportional increases in endolymph [HCO3-] and [CO32-]. Endolymph pH regulation despite the increased pCO2 suggests enhanced H+ removal. However, a lack of differences in inner ear bulk and cell-specific Na+/K+-ATPase and vacuolar type H+-ATPase protein abundance localization pointed out to activation of preexisting ATPases, non-bicarbonate pH buffering, or both, as the mechanism for endolymph pH-regulation. These results provide the first direct evidence showcasing the acid-base chemistry of the endolymph of OA-exposed fish favors otolith overgrowth, and suggests that this phenomenon will be more pronounced in species that count with more robust blood and endolymph pH regulatory mechanisms.

scholarly journals pH-regulation: the role of the hepatorenal system

1987 ◽  
Vol 6 (3) ◽  
pp. 115-117
Author(s):  
M. J. Pitout ◽  
G. T. Willemse
Keyword(s):  
Ph Regulation ◽  
Buffer System ◽  
Urea Synthesis ◽  
Ph Homeostasis ◽  
Acid Base Balance ◽  
Bicarbonate Concentration ◽  
Acid Base ◽  
Base Balance ◽  
The Relationship

The regulation of the acid-base balance is generally regarded as a well entrenched area. However, a number of confusing views on pH-homeostasis, especially with reference to the relationship between the kidney and the ammonium buffer system, appear regularly in textbooks. One reason is that the correct stoichiometry of acid-base regulation is not mentioned. Recently the rote of the liver in pH regulation by controlling the bicarbonate concentration through urea synthesis is proposed. In this paper the role of the liver and kidneys as a team is discussed.

scholarly journals The Molecular Effects of Dietary Acid Load on Metabolic Disease (The Cellular PasaDoble: The Fast-Paced Dance of pH Regulation)

2021 ◽  
Vol 1 ◽  
Author(s):  
Morgan Williamson ◽  
Naima Moustaid-Moussa ◽  
Lauren Gollahon
Keyword(s):  
Metabolic Disease ◽  
Mammalian Cells ◽  
Metabolic Diseases ◽  
Prolonged Exposure ◽  
The Body ◽  
Calcium Excretion ◽  
Ph Homeostasis ◽  
Acid Base ◽  
Dietary Analysis ◽  
Wide Range

Metabolic diseases are becoming more common and more severe in populations adhering to western lifestyle. Since metabolic conditions are highly diet and lifestyle dependent, it is suggested that certain diets are the cause for a wide range of metabolic dysfunctions. Oxidative stress, excess calcium excretion, inflammation, and metabolic acidosis are common features in the origins of most metabolic disease. These primary manifestations of “metabolic syndrome” can lead to insulin resistance, diabetes, obesity, and hypertension. Further complications of the conditions involve kidney disease, cardiovascular disease, osteoporosis, and cancers. Dietary analysis shows that a modern “Western-style” diet may facilitate a disruption in pH homeostasis and drive disease progression through high consumption of exogenous acids. Because so many physiological and cellular functions rely on acid-base reactions and pH equilibrium, prolonged exposure of the body to more acids than can effectively be buffered, by chronic adherence to poor diet, may result in metabolic stress followed by disease. This review addresses relevant molecular pathways in mammalian cells discovered to be sensitive to acid - base equilibria, their cellular effects, and how they can cascade into an organism-level manifestation of Metabolic Syndromes. We will also discuss potential ways to help mitigate this digestive disruption of pH and metabolic homeostasis through dietary change.

scholarly journals Acid-base regulation in the renal proximal tubules: using novel pH sensors to maintain homeostasis

2018 ◽  
Vol 315 (5) ◽  
pp. F1187-F1190 ◽  
Author(s):  
Premraj Rajkumar ◽  
Jennifer L. Pluznick
Keyword(s):  
Proximal Tubule ◽  
Narrow Range ◽  
Ph Regulation ◽  
Critical Role ◽  
Proximal Tubules ◽  
Ph Sensors ◽  
Ph Homeostasis ◽  
Acid Base ◽  
To Come

The kidneys play a critical role in precisely regulating the composition of the plasma to maintain homeostasis. To achieve this, the kidneys must be able to accurately determine or “sense” the concentration of a wide variety of substances and to make adjustments accordingly. Kidneys face a key challenge in the arena of pH balance, as there is a particularly narrow range over which plasma pH varies in a healthy subject (7.35–7.45) and this pH must constantly be protected against a variety of onslaughts (changes in diet, activity, and even elevation). The proximal tubule, the first segment to come into contact with the forming urine, plays an important role in helping the kidneys to maintain pH homeostasis. Recent studies have identified a number of novel proximal tubule proteins and signaling pathways that work to sense changes in pH and subsequently modulate renal pH regulation. In this review, we will highlight the role of novel players in acid-base homeostasis in the proximal tubule.

Acid-base transport in pancreatic cancer: Molecular mechanisms and clinical potential

2014 ◽  
Vol 92 (6) ◽  
pp. 449-459 ◽  
Author(s):  
Su Chii Kong ◽  
Andrea Gianuzzo ◽  
Ivana Novak ◽  
Stine Falsig Pedersen
Keyword(s):  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Ph Regulation ◽  
Treatment Options ◽  
Ductal Adenocarcinoma ◽  
Cancer Type ◽  
Ph Homeostasis ◽  
Acid Base ◽  
Acid Extrusion ◽  
Transporter Expression

Solid tumors are characterized by a microenvironment that is highly acidic, while intracellular pH (pHi) is normal or even elevated. This is the result of elevated metabolic rates in the highly proliferative cancer cells, in conjunction with often greatly increased rates of net cellular acid extrusion. Studies in various cancers have suggested that while the acid extrusion mechanisms employed are generally the same as those in healthy cells, the specific transporters upregulated vary with the cancer type. The main such transporters include Na+/H+ exchangers, various HCO3− transporters, H+ pumps, and lactate-H+ cotransporters. The mechanisms leading to their dysregulation in cancer are incompletely understood but include changes in transporter expression levels, trafficking and membrane localization, and posttranslational modifications. In turn, accumulating evidence has revealed that in addition to supporting their elevated metabolic rate, their increased acid efflux capacity endows the cancer cells with increased capacity for invasiveness, proliferation, and chemotherapy resistance. The pancreatic duct exhibits an enormous capacity for acid-base transport, rendering pHi dysregulation a potentially very important topic in pancreatic ductal adenocarcinoma (PDAC). PDAC — accounting for about 90% of all pancreatic cancers — has one of the highest cancer mortality rates known, and new diagnostic and treatment options are highly needed. However, very little is known about whether pH regulation is altered in PDAC and, if so, the possible role of this in cancer development. Here, we review current models for pancreatic acid-base transport and pH homeostasis and summarize current views on acid-base dysregulation in cancer, focusing where possible on the few studies to date in PDAC. Finally, we present new data-mining analyses of acid-base transporter expression changes in PDAC and discuss essential directions for future work.

Expression of the N-myc proto-oncogene during the early development of Xenopus laevis

Development ◽  
1990 ◽  
Vol 110 (3) ◽  
pp. 885-896
Author(s):  
P.D. Vize ◽  
A. Vaughan ◽  
P. Krieg
Keyword(s):  
Nervous System ◽  
Early Development ◽  
Cranial Nerves ◽  
Otic Vesicle ◽  
Cdna Clones ◽  
Stage Of Development ◽  
Wide Range ◽  
Mammalian Embryos ◽  
The Central Nervous System

The N-myc proto-oncogene is expressed in a wide range of tissues during mammalian embryogenesis. This observation, along with the oncogenic capacity of this gene, has led to the suggestion that N-myc plays an important role in early development. However, due to the complexity of the expression pattern and the difficulty of manipulating mammalian embryos, little progress has been made towards understanding the developmental function of this gene. To enable a more detailed analysis of the role of this gene in early development, a study of the Xenopus homologue of N-myc was undertaken. Xenopus N-myc cDNA clones were isolated from a neurula library using a murine N-myc probe. Analysis of the timing of expression of N-myc mRNA and of the distribution of N-myc protein during Xenopus development indicate that this gene may be playing an important role in the formation of a number of embryonic structures, including the nervous system. N-myc is initially expressed as a maternal RNA, but this mRNA is degraded by the gastrula stage of development. Zygotic expression does not commence until late neurula. Examination of the distribution of the N-myc protein by whole-mount immunohistochemistry indicates that the early embryonic expression occurs in the central nervous system, the neural crest, the somites and the epidermis. Later expression is mostly within the head and somites. Specific structures within the head that express the protein include the eye, otic vesicle, fore and hindbrain and a number of cranial nerves. The results demonstrate that while N-myc is expressed in the developing nervous system of Xenopus, the timing of expression indicates that it is unlikely to be involved in regulation of the very first stages of neurogenesis.

scholarly journals Rest interval duration does not influence adaptations in acid/base transport proteins following 10 wk of sprint-interval training in active women

2017 ◽  
Vol 312 (5) ◽  
pp. R702-R717 ◽  
Author(s):  
Cian McGinley ◽  
David J. Bishop
Keyword(s):  
Ph Regulation ◽  
Interval Training ◽  
Transport Protein ◽  
Monocarboxylate Transporter ◽  
Protein Abundance ◽  
Interval Duration ◽  
Rest Interval ◽  
Acid Base ◽  
Skeletal Muscle Function

The removal of protons (H+) produced during intense exercise is important for skeletal muscle function, yet it remains unclear how best to structure exercise training to improve muscle pH regulation. We investigated whether 4 wk of work-matched sprint-interval trining (SIT), performed 3 days/wk, with either 1 ( Rest-1; n = 7) or 5 ( Rest-5; n = 7) min of rest between sprints, influenced adaptations in acid/base transport protein content, nonbicarbonate muscle buffer capacity (βmin vitro), and exercise capacity in active women. Following 1 wk of posttesting, comprising a biopsy, a repeated-sprint ability (RSA) test, and a graded-exercise test, maintenance of adaptations was then studied by reducing SIT volume to 1 day/wk for a further 5 wk. After 4 wk of SIT, there was increased protein abundance of monocarboxylate transporter (MCT)-1, sodium/hydrogen exchanger (NHE)-1, and carbonic anhydrase (CA) XIV for both groups, but rest interval duration did not influence the adaptive response. In contrast, greater improvements in total work performed during the RSA test after 4 wk of SIT were evident for Rest-5 compared with Rest-1 (effect size: 0.51; 90% confidence limits ±0.37), whereas both groups had similarly modest improvements in V̇o2peak. When training volume was reduced to 1 day/wk, enhanced acid/base transport protein abundance was maintained, although NHE1 content increased further for Rest-5 only. Finally, our data support intracellular lactate as a signaling molecule for inducing MCT1 expression, but neither lactate nor H+ accumulation appears to be important signaling factors in MCT4 regulation.

As(III) Removal by Dynamic Adsorption onto Amberlite XAD7 Functionalized with Crown Ether and Doped with Fe(III) Ions

2019 ◽  
Vol 70 (7) ◽  
pp. 2330-2334
Author(s):  
Mihaela Ciopec ◽  
Adina Negrea ◽  
Narcis Duteanu ◽  
Corneliu Mircea Davidescu ◽  
Iosif Hulka ◽  
...  
Keyword(s):  
Adsorption Process ◽  
Arsenic Removal ◽  
Arsenic Concentration ◽  
Fixed Bed ◽  
World Health ◽  
Arsenic Content ◽  
Arsenic Adsorption ◽  
Stage Of Development ◽  
Wide Range ◽  
Health Organization

Arsenic content in groundwater�s present a wide range of concentration, ranging from hundreds of micrograms to thousands of micrograms of arsenic per litter, while the maximum permitted arsenic concentration established by World Health Organization (WHO) is 10 mg L-1. According to the WHO all people, regardless of their stage of development and their social economic condition, have the right to have access to adequate drinking water. The most efficient and economic technique used for arsenic removal is represented by adsorption. In order to make this remediation technique more affordable and environmentally friendly is important to new materials with advance adsorbent properties. Novelty of present paper is represented by the usage of a new adsorbent material obtained by physical - chemical modification of Amberlite XAD polymers using crown ethers followed by iron doping, due to well-known affinity of arsenic for iron ions. Present paper aims to test the obtained modified Amberlite polymer for arsenic removal from real groundwater by using adsorption in a fixed bed column, establishing in this way a mechanism for the adsorption process. During experimental work was studied the influence of competing ions from real water into the arsenic adsorption process.

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