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::Abnormal and prolonged inflammatory reaction is seen in a wide variety of disorders, and high level of Tumor Necrosis Factor alpha (TNF-α) has been linked to these disorders. Therefore, modulation of TNF-α expression is important in the regulation of inflammatory disorders. In our previous study, we have shown that a ...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/156652411796268731
更新日期:2011-08-01 00:00:00
abstract::Type 2 Diabetes occurs as a result of defects in insulin secretion and its function. Although mechanisms of disease are not fully elucidated, it is recognized that a progressive decline in insulin secretory capacity is responsible for its occurrence and natural course. Metabolic syndrome, known to be a precursor of Ty...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652409787847245
更新日期:2009-04-01 00:00:00
abstract:BACKGROUND:In this study, the antioxidant property of new synthesized azomethins has been investigated as theoretical and experimental. METHODS AND RESULTS:Density functional theory (DFT) was employed to investigate the Bond Dissociation Enthalpy (BDE), Mulliken Charges, NBO analysis, Ionization Potential (IP), Electr...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524019666190509102620
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Four-and-a-half LIM domains protein 1 (FHL1) mutations are associated with human myopathies. However, the function of this protein in skeletal development remains unclear. METHODS:Whole-mount in situ hybridization and embryo immunostaining were performed. RESULTS:Zebrafish Fhl1A is the homologue of human F...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524018666180308113909
更新日期:2017-01-01 00:00:00
abstract::Since the discovery almost fifteen years ago that E2F transcription factors are key targets of the retinoblastoma protein (RB), studies of the E2F family have uncovered critical roles in the control of transcription, cell cycle and apoptosis. E2F proteins are encoded by at least eight genes, E2F1 through E2F8. While s...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524010606070739
更新日期:2006-11-01 00:00:00
abstract:BACKGROUND:Seven isoforms of histone deacetylase Class III have been reported - Sirtuin (SIRT) 1-7. We recently demonstrated that EX-527, an inhibitor of SIRT1, reduces mortality in a mouse model of lethal-cecal-ligationand- puncture (CLP)-induced septic shock. Our present study was aimed at determining whether selecti...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/156652401507150903185852
更新日期:2015-01-01 00:00:00
abstract::In sum, the FTIs are signal transduction inhibitors that display promising clinical activity against a broad spectrum of malignancies. We are just beginning to explore and elucidate the mechanisms by which transformed cells respond to FTIs and the optimal settings in which they do so. The clinical trials that are curr...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652405774641052
更新日期:2005-11-01 00:00:00
abstract::Until recently it was believed that TNF-induced apoptosis is mediated exclusively by TNF-RI because TNF-RII lacks death domain. However, it has been demonstrated that TNF-RII enhances TNF-RI-mediated apoptosis. In this review, I have discussed the evidence and mechanisms by which TNF-RII regulates TNF-alpha-induced ap...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524013363780
更新日期:2001-07-01 00:00:00
abstract::p66Shc is the only known proapoptotic member of the Shc protein family of molecular adaptors. Through its redox activity, p66Shc oxidates cytochrome-c, leading to increased ROS production and, eventually, to apoptosis. p66Shc has been implicated in the control of oxidative stress and life span in mammals. In this revi...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652409787847254
更新日期:2009-04-01 00:00:00
abstract::The role of mitochondrial DNA (mtDNA) variant 16189T>C in type 2 diabetes mellitus (T2DM) remains hotly debated in the past decade. If mutation 16189T>C indeed posed a risk to T2DM, as echoed by some recent studies, correlation between this mutation and disease should be observed when carrying out a systematical study...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524014666141202161326
更新日期:2014-01-01 00:00:00
abstract::Despite advances in biomedical sciences, the prognosis of patients with brain tumors remains poor. Effective treatment is lacking for these central nervous system (CNS) cancers. Targeted immunotoxins are a new class of therapeutic approaches that have emerged for the treatment of human cancers. In this approach, tumor...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652409788970661
更新日期:2009-08-01 00:00:00
abstract::The mitochondrial 18 kDa Translocator Protein (TSPO) was first detected by its capability to bind benzodiazepines in peripheral tissues and later also in glial cells in the brain, hence its previous most common name peripheral benzodiazepine receptor (PBR). TSPO has been implicated in various functions, including apop...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524011207040398
更新日期:2012-05-01 00:00:00
abstract::Conformational or misfolding diseases are a large class of devastating human disorders associated with protein misfolding and aggregation. Most conformational diseases are caused by a combination of genetic and environmental factors, suggesting that spontaneous events can destabilize the protein involved in the pathol...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652408783565595
更新日期:2008-02-01 00:00:00
abstract::Bone marrow-derived mesenchymal stem cells (BMSCs) can be recruited to tumor sites and integrate into the stroma of tumors. When co-cultured with BMSCs, otherwise weakly metastatic nasopharyngeal carcinoma cells (NPC) showed improved metastatic ability. BMSCs in the tumor environment displayed the characteristics of m...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524014666140724102301
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Dynamic epigenetic alterations accompanying CD4+ T helper cell differentiation have been implicated in multiple autoimmune diseases. The bromodomain and extra-terminal (BET) proteins are epigenetic regulators that recognize and bind to acetylated histones in chromatin and are targets for pharmacological inhi...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524019666190126112238
更新日期:2018-01-01 00:00:00
abstract::The leading cause of blindness in the developed world results from several disorders that have pathologic ocular neovascularization as the common pathway leading to vision loss. These disorders include exudative age related macular degeneration (AMD), diabetic retinopathy (DR), retinopathy of prematurity (ROP), retina...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652409789712783
更新日期:2009-11-01 00:00:00
abstract:PURPOSE:Ubiquitin is involved in cell proliferation and differentiation, and the objective of this study is to investigate the potential of dominant negative Ubiquitin (Ub) with a lysine to tryptophan mutation at the 6 position (K6W) through an adenoviral expression vector in the prevention of posterior capsule opacifi...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524017666170331163751
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Osteoporosis is a systemic skeletal disease characterized by low bone mineral density. Vitamin D metabolism may play a pivotal role in its pathophysiology. OBJECTIVES:To determine the association between Vitamin D receptor gene polymorphisms and bone density, as well as its relation to biochemical markers o...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524019666190409122155
更新日期:2019-01-01 00:00:00
abstract::The testes are one of the most delicate organs in the male body and highly susceptible to the exogenous influences capable of inducing cell damage. Cancer therapies are well known to negatively affect the male reproductive tract with a severe impairment of spermatogenesis and infertility. The present work aimed to sys...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524016666160802150400
更新日期:2016-01-01 00:00:00
abstract::Skeletal mass is regulated by the coordinated action of bone forming osteoblasts and bone resorbing osteoclasts. Accelerated rates of bone resorption relative to bone formation lead to net bone loss and the development of osteoporosis, a devastating disease that predisposes the skeleton to fractures. Bone fractures ar...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524014666140724104842
更新日期:2014-01-01 00:00:00
abstract:OBJECTIVES:Celastrol, a quinone methide triterpenoid, could induce apoptosis in pancreatic cancer cells. The purpose of this study is to determine whether there is protective autophagy after celastrol treatment in pancreatic cancer cells and the synergistic effects of celastrol and 3-MA in vitro and in vivo. METHODS:T...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524014666140414211223
更新日期:2014-05-01 00:00:00
abstract::Citrate is one of the major substrates for intracellular metabolism. The extracellular level of citrate is stable in blood but varies locally, with slightly increased levels in brain and high levels in prostate. Recent metabolomics research suggests that citrate level is a potential harbinger of different pathophysiol...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524016666151123104855
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Photoreceptor cell death is a key pathology of retinal degeneration diseases. To date, the molecular mechanisms for this pathological process remain largely unclear. Junctional adhesion molecule-c (Jam-c) has been shown to play important roles in different biological events. However, its effect on retinal ne...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524018666180212144500
更新日期:2018-03-09 00:00:00
abstract::Our current understanding of the mechanisms of information processing and storage in the brain, based on the concept proposed more than fifty years ago by D. Hebb, is that a key role is played by changes in synaptic efficacy induced by coincident pre- and postsynaptic activity. Decades of studies of the properties of ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524023362041
更新日期:2002-11-01 00:00:00
abstract:OBJECTIVE:To detect mutations of trypsinogen gene (PRSS1) in patients with autoimmune pancreatitis (AIP) and to determine the underlying pathogenesis. METHODS:DNA sequencing was used to detect full-length of PRSS1, cystic fibrosis transmembrane conductance regulator (CFTR), and pancreatic secretory trypsin inhibitor (...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524013666131118114432
更新日期:2014-03-01 00:00:00
abstract::In this study, a two-dimensional gel-based proteomic approach was applied to profile the protein alterations underlying the significant adverse effects from post-stroke depression (PSD). In view of the close association between left prefrontal cortical dysfunction and PSD, a PSD rat model was constructed through a lef...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524014666141021143333
更新日期:2014-01-01 00:00:00
abstract::N-methyl-D-aspartate (NMDA) receptor plays important roles in learning and memory. NMDA receptors are a tetramer that consists of two glycine-binding subunits GluN1, two glutamate-binding subunits (i.e., GluN2A, GluN2B, GluN2C, and GluN2D), a combination of a GluN2 subunit and glycine-binding GluN3 subunit (i.e., GluN...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524015666150330142807
更新日期:2015-01-01 00:00:00
abstract::Human genetic data on psychiatric disorders repeatedly demonstrate the involvement of various genes that are associated with neural development and neurogenesis. Neurogenesis is a biological process that is critical in brain development and continues throughout life. Neurogenesis is a multi-step process starting from ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524015666150303002834
更新日期:2015-01-01 00:00:00
abstract::Focal cerebral ischemia induces neurogenesis in the subventricular zone (SVZ) of the adult human brain. Neurogenesis is controlled by proliferation, differentiation, and migration of neural progenitor cells. This article reviews emerging data that changes of cell cycle kinetics of neural progenitor cells induced by st...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652407781387136
更新日期:2007-08-01 00:00:00
abstract::p53 tumor suppressor plays a pivotal role in maintaining genomic integrity and preventing cancer development. The importance of p53 in tumor suppression is illustrated by the observation that about 50% human tumor cells have a dysfunctional p53 pathway. Although it has been well accepted that the activity of p53 is ma...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652408786733748
更新日期:2008-12-01 00:00:00