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 pathophysiological states; its decrease has been correlated with male infertility, brain diseases and metastatic cancer. In this review we discuss the role of citrate as an energy substrate for sperm. We also review the function of citrate released by astrocytes in the normal operation of neurons, and consequently we suggest a potential role of neuronal plasma membrane citrate transporters in mental disorders. Finally, we review recent relevant publications studying blood, urine and tissue citrate levels in cancer patients and hypothesize that extracellular citrate supports cancer cell metabolism critical for metastasis. Despite the importance of extracellular citrate in physiological and pathophysiological processes, surprisingly little is known about citrate synthesis in specialized cells, or about citrate transporters controlling citrate movement across various membranes. Determination of the molecular origin of citrate transporters in astrocytes, sperm and cancer cells could offer novel therapeutic targets and the possibility to pharmacologically regulate citrate release and uptake for preventing male infertility, treating mental diseases and targeting cancer.
journal_name
Curr Mol Medjournal_title
Current molecular medicineauthors
Mycielska ME,Milenkovic VM,Wetzel CH,Rümmele P,Geissler EKdoi
10.2174/1566524016666151123104855subject
Has Abstractpub_date
2015-01-01 00:00:00pages
884-91issue
10eissn
1566-5240issn
1875-5666pii
CMM-EPUB-72039journal_volume
15pub_type
杂志文章,评审abstract::Although surgery and radiotherapy are highly efficient in local tumor control, distal metastases and tumor recurrence often limit therapeutic outcome. It is becoming progressively more evident that curative tumor therapy depends on the presence and maintenance of an intact immune system which has the capacity to elici...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652412803306666
更新日期:2012-11-01 00:00:00
abstract:PURPOSE:To evaluate cytokine expression profile in aqueous humor and sera in patients with HLAB27 associated acute anterior uveitis (AAU) and idiopathic AAU. METHODS:Twenty patients with AAU and 17 controls were recruited from August 2012 to March 2013. Study subjects with uveitis were divided into two groups: 9 patie...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524015666150731100012
更新日期:2015-01-01 00:00:00
abstract::There has been prolonged and significant interest in manipulating the genome for a wide range of applications in biomedical research and medicine. An existing challenge in realizing this potential has been the inability to precisely edit specific DNA sequences. Past efforts to generate targeted double stranded DNA cle...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524016666160316150847
更新日期:2016-01-01 00:00:00
abstract::Maintenance of ex vivo hematopoietic stem cells (HSC) pool and its differentiated progeny is regulated by complex network of transcriptional factors, cell cycle proteins, extracellular matrix, and their microenvironment through an orchestrated fashion. Strides have been made to understand the mechanisms regulating in ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652412798376125
更新日期:2012-01-01 00:00:00
abstract::As tumors progress to increased malignancy, cells within them develop the ability to invade into surrounding normal tissues and through tissue boundaries to form new growths (metastases) at sites distinct from the primary tumor. The molecular mechanisms involved in this process are incompletely understood but those as...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524033479447
更新日期:2003-11-01 00:00:00
abstract::Evidence shows that artificially lowering body and brain temperature can significantly reduce the deleterious effects of brain injury in both newborns and adults. Although the benefits of therapeutic hypothermia have long been known and applied clinically, the underlying molecular mechanisms have yet to be elucidated....
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652412803833517
更新日期:2012-12-01 00:00:00
abstract::Several species of kinetoplastid protozoa cause major human infectious diseases. Trypanosoma cruzi is responsible for the fatal Chagas disease in large parts of South America, the various species of Leishmania cause a number of different human diseases with millions of patients world-wide, and the African trypanosome ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
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更新日期:2004-09-01 00:00:00
abstract::Immune tolerance can be induced by numerous methods. This review article aims to draw lines of similarity and contrast between two unique models of immune tolerance, namely Anterior Chamber Associated Immune Deviation (ACAID) and Nickel-induced oral tolerance. ACAID is an immune tolerance model that leads to the gener...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524015666150114114602
更新日期:2015-01-01 00:00:00
abstract::The structure and developmental mechanisms of vertebrate retina are highly conserved. One of the most distinctive events during retinogenesis is the temporally and spatially generation of seven types of retinal cells from the multipotent retinal progenitor cells. The importance and prevalence of SUMOylation in regulat...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524016666161128115453
更新日期:2016-01-01 00:00:00
abstract::Non-alcoholic fatty liver disease (NAFLD) is a clinico-pathologic spectrum of conditions ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). Although simple or bland steatosis follows a relatively benign clinical course, NASH can potentially progress to cirrhosis (approximately 10 to 15 percent) and ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652410790963321
更新日期:2010-03-01 00:00:00
abstract::The identification of a relevant effector of Ran GTPase (Ran) signaling and its pathways could provide a novel approach to cancer therapeutics. With recent research highlighting the significant relationship between Ran expression and the occurrence and progression of cancer, the development of a small molecule compoun...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652411797536688
更新日期:2011-11-01 00:00:00
abstract::Although it has been known for long time that atherosclerosis is associated with lipid deposition, only recently it has been accepted that the plasmatic concentration of cholesterol, especially LDL cholesterol, is a risk factor for atherosclerosis. However, chemically modified LDL, but not native LDL, is able to induc...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524023362177
更新日期:2002-09-01 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:PURPOSE:Retinal ganglion cells (RGCs) apoptosis is a common characteristic of optic neuropathies. p53-induced protein with a death domain (PIDD) is a well-known regulator of genotoxic stress-induced apoptosis, which is constitutively cleaved into three main fragments: PIDD-N, PIDD-C and PIDD-CC. Thus, we aim to determi...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524019666190918160032
更新日期:2019-01-01 00:00:00
abstract::Central Nervous System (CNS) tuberculosis is a serious, often fatal form of tuberculosis, predominantly affecting young children. HIV co-infection and drug resistant strains of Mycobacterium tuberculosis are making the diagnosis and treatment of CNS tuberculosis more complicated. Current concepts about the pathogenesi...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652409787581655
更新日期:2009-03-01 00:00:00
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
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::Human induced pluripotent stem cells (hiPSCs) have great potential as a robust source of progenitors for regenerative medicine. The novel technology also enables the derivation of patient-specific cells for applications to personalized medicine, such as for personal drug screening and toxicology. However, the biologic...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524011313050010
更新日期:2013-06-01 00:00:00
abstract::Islet cell transplantation is an attractive alternative therapy to conventional insulin treatment or vascularized whole pancreas transplantation for type 1 diabetic patients. It represents a successful example of somatic cell therapy in humans based on complex procedures for islet isolation from whole pancreas. The is...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652406777435453
更新日期:2006-06-01 00:00:00
abstract::The ocular lens is a non-vascular and non-innervated transparent organ that plays an important role in vision processing. This unique organ is derived from the embryonic ectoderm of the brain region through a complicated differentiation process in which apoptosis plays a key role. First, when the committed ectoderm be...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652410793937741
更新日期:2010-12-01 00:00:00
abstract::Gastric cancer is thought to result from a combination of environmental factors and the accumulation of specific genetic alterations due to increasing genetic instability, and consequently affects mainly older patients. Less than 10% of patients present with the disease before 45 years of age (early onset gastric carc...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652407779940503
更新日期:2007-02-01 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::Induced pluripotent stem (iPS) cell research has been growing a new height throughout the world due to its potentialities in medical applications. We can explore several therapeutic applications through the iPS cell research. In this review, we have first discussed the development of iPS cells, reprogramming factors, ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652410793384178
更新日期:2010-11-01 00:00:00
abstract:BACKGROUND:Obesity is a chronic condition associated with poorer cognitive functioning. Wisconsin Card Sorting Test (WCST) is a useful tool for evaluating executive functions. In this study, we assessed the association between dopaminergic gene polymorphisms: DAT1 (SLC6A3), COMTVal158Met, DRD4 (48-bp variable number of...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524019666190424143653
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:The phenotypic severity of β-thalassemia is highly modulated by three genetic modifiers: β-globin (HBB) mutations, co-inheritance of α-thalassemia and polymorphisms in the genes associated with fetal haemoglobin (HbF) production. This study was aimed to evaluate the effect of HbF related polymorphisms mainly...
journal_title:Current molecular medicine
pub_type: 临床试验,杂志文章
doi:10.2174/1566524018666181004121604
更新日期:2018-01-01 00:00:00
abstract::Type 2 diabetes (T2D) is a metabolic disorder characterised by the inability of β-cells to secrete enough insulin to maintain glucose homeostasis. Pancreatic β-cells secrete insulin in a biphasic manner, first and second phase insulin secretion, and loss of first phase insulin secretion is an independent predictor of ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:
更新日期:2013-01-01 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::Liver cirrhosis, an end-result of a wide variety of the liver diseases, is a world wide health problem. Because of its unique organ system, i.e., portal blood supply, bile formation and enterohepatic circulation, drug metabolism system, and sinusoidal lining cells such as Kupffer, endothelial and stellate cells, the l...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
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更新日期:2003-09-01 00:00:00
abstract::In recent years, the clinical validation of molecular targeted therapies inhibiting the action of pathogenic tyrosine kinase (TK) has been one of the most exciting developments in cancer research. In this context, medullary thyroid carcinoma (MTC) represents a promising model. It is well known that in MTC, the RET rec...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652410792630607
更新日期:2010-10-01 00:00:00
abstract::Hypoxia is a major hallmark of the tumor microenvironment that is strictly associated with rapid cancer progression and induction of metastasis. Hypoxia inhibits disulfide bond formation and impairs protein folding in the Endoplasmic Reticulum (ER). The stress in the ER induces the activation of Unfolded Protein Respo...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524016666160523143937
更新日期:2016-01-01 00:00:00