Abstract:
:The view that mitochondrial electron transport is the only site of aerobic respiration and the primary bioenergetic pathway in mammalian cells is well established in the literature. Although this paradigm is widely accepted for most tissues, the situation is less clear for proliferating cells. Increasing evidence indicates that glycolytic ATP production contributes substantially to fulfilling the energy requirements of rapidly dividing somatic cells, many tumour cells, and self-renewing stem cells in hypoxic environments. Glycolytic cells have been shown to consume oxygen at the cell surface via plasma membrane electron transport (PMET), a process that oxidises intracellular NADH, supports glycolytic ATP production and may contribute to aerobic energy production. PMET, as determined by reduction of a cell-impermeable tetrazolium dye, is highly active in rapidly-dividing tumour cell lines, where it ameliorates intracellular reductive stress, originating from the mitochondrial TCA cycle. Thus, mitochondrial NADH production is linked to dye reduction outside the cell via the malate-aspartate shuttle. PMET activity increases several-fold under hypoxic conditions, consistent with the view that oxygen competes for electrons from this PMET system. In addition, rho(o) cells that lack mitochondrial electron transport are characterised by elevated PMET presumably to recycle NADH, a role traditionally assumed by lactate dehydrogenase. PMET presents an excellent target for developing novel anticancer drugs that exploit its unique plasma membrane localisation. We propose that PMET is a ubiquitous, high-capacity acute NADH redox-regulatory system responsible for maintaining the mitochondrial NADH/NAD+ ratio. Blocking this pathway compromises the viability of rapidly proliferating cells that rely on PMET.
journal_name
Curr Mol Medjournal_title
Current molecular medicineauthors
Herst PM,Berridge MVdoi
10.2174/156652406779010777subject
Has Abstractpub_date
2006-12-01 00:00:00pages
895-904issue
8eissn
1566-5240issn
1875-5666journal_volume
6pub_type
杂志文章,评审abstract::Autophagy is a bulk cytosolic degradative process which in the last few years has become a key pathway for the advancement of molecular medicine. Autophagy (cellular self-eating) has several implications in human disorders involving accumulation of cytosolic protein aggregates such as Alzheimer, Parkinson, Huntington ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652408783769634
更新日期:2008-03-01 00:00:00
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journal_title:Current molecular medicine
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journal_title:Current molecular medicine
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doi:10.2174/156652410792630607
更新日期:2010-10-01 00:00:00
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journal_title:Current molecular medicine
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更新日期:2004-12-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2005-11-01 00:00:00
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journal_title:Current molecular medicine
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更新日期:2005-12-01 00:00:00
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journal_title:Current molecular medicine
pub_type: 杂志文章,评审
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更新日期:2005-09-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2012-09-01 00:00:00
abstract::Ca2+ ions are involved in the regulation of many diverse functions in animal and plant cells, e.g. muscle contraction, secretion of neurotransmitters, hormones and enzymes, fertilization of oocytes, and lymphocyte activation and proliferation. The intracellular Ca2+ concentration can be increased by different molecula...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
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更新日期:2002-05-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2007-11-01 00:00:00
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pub_type: 杂志文章
doi:10.2174/156652412803833535
更新日期:2012-12-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2008-12-01 00:00:00
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更新日期:2005-02-01 00:00:00
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journal_title:Current molecular medicine
pub_type: 杂志文章,评审
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更新日期:2011-12-01 00:00:00
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journal_title:Current molecular medicine
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更新日期:2010-04-01 00:00:00
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journal_title:Current molecular medicine
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更新日期:2010-12-01 00:00:00
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journal_title:Current molecular medicine
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更新日期:2020-01-01 00:00:00
abstract:PURPOSE:A small molecular compound, aminooxy-acetic acid (AOA), has been shown to modulate experimental autoimmune encephalomyelitis (EAE). The current study was designed to investigate whether AOA has a similar effect on the development of experimental autoimmune uveitis (EAU) and to further explore underlying mechani...
journal_title:Current molecular medicine
pub_type: 杂志文章
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更新日期:2020-01-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2006-02-01 00:00:00
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journal_title:Current molecular medicine
pub_type: 杂志文章,评审
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更新日期:2002-06-01 00:00:00
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journal_title:Current molecular medicine
pub_type: 杂志文章,评审
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更新日期:2012-01-01 00:00:00
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journal_title:Current molecular medicine
pub_type: 临床试验,杂志文章
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更新日期:2018-01-01 00:00:00
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journal_title:Current molecular medicine
pub_type: 杂志文章,评审
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更新日期:2007-06-01 00:00:00
abstract::Strong epidemiological evidence indicates that migraine, especially migraine with aura, is associated with increased risk of ischemic stroke. However, the precise mechanisms of such a relation are currently not fully elucidated and are still a matter of speculation. Migraine may directly cause an ischemic event (i.e, ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
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更新日期:2009-03-01 00:00:00
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journal_title:Current molecular medicine
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更新日期:2020-01-01 00:00:00
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journal_title:Current molecular medicine
pub_type: 杂志文章,评审
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更新日期:2012-12-01 00:00:00
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journal_title:Current molecular medicine
pub_type: 杂志文章,评审
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更新日期:2012-07-01 00:00:00