Abstract:
:The acid-base balance of cells is related to the concentration of free H⁺ ions. These are highly reactive, and their intracellular concentration must be regulated to avoid detrimental effects to the cell. H⁺ ion dynamics are influenced by binding to chelator substances ('buffering'), and by the production, diffusion and membrane-transport of free H⁺ ions or of the H⁺-bound chelators. Intracellular pH (pHi) regulation aims to balance this system of diffusion-reaction-transport processes at a favourable steady-state pHi. The ability of cells to regulate pHi may set a limit to tissue growth and can be subject to selection pressures. Cancer cells have been postulated to respond favourably to such selection pressures by evolving a better means of pHi regulation. A particularly important feature of tumour pHi regulation is acid-extrusion, which involves H⁺-extrusion and HCO₃⁻-uptake by membrane-bound transporter-proteins. Extracellular CO₂/HCO₃⁻ buffer facilitates these membrane-transport processes. As a mobile pH-buffer, CO₂/HCO₃⁻ protects the extracellular space from excessive acidification that could otherwise inhibit further acid-extrusion. CO₂/HCO₃⁻ also provides substrate for HCO₃⁻-transporters. However, the inherently slow reaction kinetics of CO₂/HCO₃⁻ can be rate-limiting for acid-extrusion. To circumvent this, cells can express extracellular-facing carbonic anhydrase enzymes to accelerate the attainment of equilibrium between CO₂, HCO₃⁻ and H⁺. The acid-extrusion apparatus has been proposed as a target for anti-cancer therapy. The major targets include H⁺ pumps, Na⁺/H⁺ exchangers and carbonic anhydrases. The effectiveness of such therapy will depend on the correct identification of rate-limiting steps in pHi regulation in a specific type of cancer.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Hulikova A,Harris AL,Vaughan-Jones RD,Swietach Pdoi
10.2174/138161212799504920subject
Has Abstractpub_date
2012-01-01 00:00:00pages
1331-7issue
10eissn
1381-6128issn
1873-4286pii
CPD-EPUB-20120223-010journal_volume
18pub_type
杂志文章,评审abstract::Alzheimer's disease (AD) is a heterogeneous and progressive neurodegenerative disease which in Western society mainly accounts for clinical dementia. Inflammation plays a key role in AD and dissecting the genetics of inflammation may provide an answer to the possible treatment. Hence, the better understanding of diffe...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161208786264089
更新日期:2008-01-01 00:00:00
abstract::The present mini review offers a brief overview on the preparation and modification of gold nanomaterials (AuNMs) designed for biomedical applications, including biosensors, bioimaging, phototherapy and importantly gene/drug delivery. As biocompatibility is a prerequisite for safe pharmaceutical application, the poten...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151210123225
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journal_title:Current pharmaceutical design
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doi:10.2174/138161206777442083
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journal_title:Current pharmaceutical design
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doi:10.2174/1381612824666180813093420
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journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128112092395
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journal_title:Current pharmaceutical design
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doi:10.2174/1381612826666200610184433
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journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161209789649484
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journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:1999-12-01 00:00:00
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journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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abstract:: ...
journal_title:Current pharmaceutical design
pub_type: 社论
doi:10.2174/138161282422181019144120
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journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023392630
更新日期:2002-01-01 00:00:00
abstract::The snake is the symbol of medicine due to its association with Asclepius, the Greek God of medicine, and so with good reasons. More than 725 species of venomous snakes have toxins specifically evolved to exert potent bioactivity in prey or victims, and snakebites constitute a public health hazard of high impact in As...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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更新日期:2016-01-01 00:00:00
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journal_title:Current pharmaceutical design
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doi:10.2174/1381612824666171201115126
更新日期:2018-01-01 00:00:00
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journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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更新日期:2013-01-01 00:00:00
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journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788682235
更新日期:2009-01-01 00:00:00
abstract::High molecular weight kininogen (HK) is a plasma protein that is cleaved by plasma kallikrein in the clinical settings of sepsis and chronic inflammatory diseases such as rheumatoid arthritis and Crohn's disease. This proteolytic event results in a nonapeptide, bradykinin (BK), and a kinin-free derivative of HK, namel...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206777698710
更新日期:2006-01-01 00:00:00
abstract:Background:Capsinoids (CSN), the novel non-pungent capsaicin analogs have been reported to promote metabolic health and exercise tolerance. However, the effect of CSN on fat oxidation and changes in skeletal muscle glycogen levels during post-exercise recovery has not been investigated in humans. Purpose:We examined t...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200824104856
更新日期:2020-08-23 00:00:00
abstract::The integrin family of cell surface receptors were principally thought to be involved in cell adhesion. Intense study has shown that these glycoproteins also regulate a diverse range of physiological processes. Inappropriate activation of integrins has been implicated in many pathological processes. Recent studies hav...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208783413284
更新日期:2008-01-01 00:00:00
abstract::Guidelines for the treatment of hypertension allow a wide range of choices to the physicians; however some differences are present about the preferred drugs to start treatment. The most important aim remains an adequate decrease of blood pressure, something not perfectly obtained in the general population, but some cl...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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abstract::The frequency of neuropsychiatric disorders is greater than that of cancer, cardiovascular disease, and diabetes combined, and is growing at a faster rate than any other ailments in the United States or Europe. Despite a considerable need for the development of treatments for central nervous system disorders, pharmace...
journal_title:Current pharmaceutical design
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更新日期:2016-01-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2010-01-01 00:00:00
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journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666181127102311
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:At sufficient sun exposure, humans can synthesize vitamin D3 endogenously in their skin, but today's lifestyle makes the secosteroid a true vitamin that needs to be taken up by diet or supplementation with pills. The vitamin D3 metabolite 1α,25-dihydroxyvitamin D3 acts as a nuclear hormone activating the tra...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190705193227
更新日期:2019-01-01 00:00:00
abstract::A positive relationship between stress tolerance and longevity has been observed in several model systems. That the same correlation is applicable in humans and that it may be open to experimental manipulation for extending human lifespan requires studies on association of stress genes with longevity. The involvement ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161210790883499
更新日期:2010-01-01 00:00:00
abstract::Human heart has endogenous regenerative capability; however, the intrinsic repair mechanism is not sufficient to overcome the impact placed by adverse pathological conditions, such as myocardial infarction (MI). In such circumstances, the damaged tissue initiates a series of remodeling process which results in the det...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150302153138
更新日期:2015-01-01 00:00:00
abstract::The metabolic syndrome (MetS) represents a cluster of medical disorders, such as hyperglycemia, dyslipidemia, hypertension, and abdominal obesity that, when occurring together, increase the risk of developing cardiovascular disease. The role of food and nutrients in the aetiology of chronic diseases has become clearer...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612819666131206112144
更新日期:2014-01-01 00:00:00
abstract::Pyrimidine nucleotides, including UTP, UDP and UDP-glucose, are important signaling molecules which activate G protein-coupled membrane receptors of the P2Y family. Four distinct pyrimidine nucleotide-sensitive P2Y receptor subtypes have been cloned, P2Y(2), P2Y(4), P2Y(6) and P2Y(14). Pharmacological experiments indi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023392937
更新日期:2002-01-01 00:00:00
abstract::We set up two models of gastric bleeding in rats using low-dose aspirin (ASA) and the antiplatelet drug clopidogrel, a P2Y₁₂ receptor antagonist, and examined the effect of antiulcer drugs on gastric bleeding and ulcerogenic responses under such conditions. Under urethane anesthesia, two catheters were inserted into t...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/13816128113199990418
更新日期:2014-01-01 00:00:00