UCP2 Dotaz Zobrazit nápovědu
Background: Discovery of uncoupling protein 2 (UCP2) in 1997 and demonstration of its wide tissue expressionhas triggered an important question about controlled oxidative phosphorylation uncoupling and the physiologicalfunction of this process. Uncoupling protein 2 (UcP2) is a mitochondrial protein that can infl uence the mitochondrialmembrane potential and hence the production of reactive oxygen species by mitochondria. It is also thought to beinvolved in apoptotic signaling pathways and it has been suggested to be important in cardio- and neuroprotection.Methods and results: We examined the recent literature (2003–2007) in the MedLine database for evidence linkingp38, one of the stress-related protein kinases, with modulation of UCP2 expression in the heart. While two reportsclearly demonstrate p38 as down-regulating UcP2 expression, only circumstantial evidence exists for cardiomyocytes.Confl icting results on p38-regulated cardiomyocyte survival after ischemia leave an open venue for hypotheses on thediff erential regulation of protein expression, including UCP2. Conclusions: Reviewing the evidence connecting UCP2 and its cytoprotective activities, we propose a tissue specifi clink that may explain the variable infl uence of p38 via modulation of UCP2 expression.
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- financování organizované MeSH
- iontové kanály MeSH
- ischemická choroba srdeční enzymologie MeSH
- kardiomyocyty metabolismus účinky léků MeSH
- kardiotonika farmakologie terapeutické užití MeSH
- lidé MeSH
- medicína založená na důkazech MeSH
- MEDLINE využití MeSH
- mitochondriální proteiny MeSH
- mitogenem aktivované proteinkinasy p38 MeSH
- oxidativní fosforylace MeSH
- reaktivní formy kyslíku chemie metabolismus MeSH
- rozpřahující látky chemie MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Research on brown adipose tissue and its hallmark protein, mitochondrial uncoupling protein UCP1, has been conducted for half a century and has been traditionally studied in the Institute of Physiology (AS CR, Prague), likewise UCP2 residing in multiple tissues for the last two decades. Our group has significantly contributed to the elucidation of UCP uncoupling mechanism, fully dependent on free fatty acids (FFAs) within the inner mitochondrial membrane. Now we review UCP2 physiological roles emphasizing its roles in pancreatic beta-cells, such as antioxidant role, possible tuning of redox homeostasis (consequently UCP2 participation in redox regulations), and fine regulation of glucose-stimulated insulin secretion (GSIS). For example, NADPH has been firmly established as being a modulator of GSIS and since UCP2 may influence redox homeostasis, it likely affects NADPH levels. We also point out the role of phospholipase iPLA2 isoform gamma in providing FFAs for the UCP2 antioxidant function. Such initiation of mild uncoupling hypothetically precedes lipotoxicity in pancreatic beta-cells until it reaches the pathological threshold, after which the antioxidant role of UCP2 can be no more cell-protective, for example due to oxidative stress-accumulated mutations in mtDNA. These mechanisms, together with impaired autocrine insulin function belong to important causes of Type 2 diabetes etiology.
- MeSH
- antioxidancia metabolismus MeSH
- beta-buňky metabolismus MeSH
- glukosa metabolismus MeSH
- inzulin biosyntéza MeSH
- iontové kanály metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- mitochondriální proteiny metabolismus MeSH
- mitochondrie metabolismus MeSH
- oxidace-redukce MeSH
- oxidační stres fyziologie MeSH
- reaktivní formy kyslíku metabolismus MeSH
- regulace genové exprese fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Existing controversies led us to analyze absolute mRNA levels of mitochondrial uncoupling proteins (UCP1-UCP5). Individual UCP isoform mRNA levels varied by up to four orders of magnitude in rat and mouse tissues. UCP2 mRNA content was relatively high (0.4 to 0.8 pg per 10 ng of total mRNA) in rat spleen, rat and mouse lung, and rat heart. Levels of the same order of magnitude were found for UCP3 mRNA in rat and mouse skeletal muscle, for UCP4 and UCP5 mRNA in mouse brain, and for UCP2 and UCP5 mRNA in mouse white adipose tissue. Significant differences in pattern were found for rat vs. mouse tissues, such as the dominance of UCP3/UCP5 vs. UCP2 transcript in mouse heart and vice versa in rat heart; or UCP2 (UCP5) dominance in rat brain contrary to 10-fold higher UCP4 and UCP5 dominance in mouse brain. We predict high antioxidant/antiapoptotic UCP function in tissues with higher UCP mRNA content.
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- DNA primery genetika MeSH
- druhová specificita MeSH
- iontové kanály metabolismus MeSH
- krysa rodu rattus MeSH
- membránové transportní proteiny metabolismus MeSH
- messenger RNA metabolismus MeSH
- mitochondriální proteiny metabolismus MeSH
- mozek metabolismus MeSH
- myokard metabolismus MeSH
- myši MeSH
- plíce metabolismus MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- proteiny nervové tkáně metabolismus MeSH
- slezina metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- MeSH
- Escherichia coli metabolismus MeSH
- finanční podpora výzkumu jako téma MeSH
- lidé MeSH
- mastné kyseliny chemie metabolismus MeSH
- membránové transportní proteiny fyziologie metabolismus MeSH
- mitochondriální proteiny fyziologie MeSH
- mitochondrie fyziologie MeSH
- transport proteinů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- abstrakt z konference MeSH
The purpose of this study was to investigate individually and in combination the association between the ACE (I/D), NOS3 (Glu298Asp), BDKRB2 (-9/+9), UCP2 (Ala55Val) and AMPD1 (Gln45Ter) variants with endurance performance in a large, performance-homogenous cohort of elite Polish half marathoners. The study group consisted of 180 elite half marathoners: 76 with time < 100 minutes and 104 with time > 100 minutes. DNA of the subjects was extracted from buccal cells donated by the runners and genotyping was carried out using an allelic discrimination assay with a C1000 Touch Thermal Cycler (Bio-Rad, Germany) instrument with TaqMan® probes (NOS3, UCP2, and AMPD1) and a T100™ Thermal Cycler (Bio-Rad, Germany) instrument (ACE and BDKRB2). We found that the UCP2 Ala55Val polymorphism was associated with running performance, with the subjects carrying the Val allele being overrepresented in the group of most successful runners (<100 min) compared to the >100 min group (84.2 vs. 55.8%; OR = 4.23, p < 0.0001). Next, to assess the combined impact of 4 gene polymorphisms, all athletes were classified according to the number of 'endurance' alleles (ACE I, NOS3 Glu, BDKRB2 -9, UCP2 Val) they possessed. The proportion of subjects with a high (4-7) number of 'endurance' alleles was greater in the better half marathoners group compared with the >100 min group (73.7 vs. 51.9%; OR = 2.6, p = 0.0034). These data suggest that the likelihood of becoming an elite half marathoner partly depends on the carriage of a high number of endurance-related alleles.
- Publikační typ
- časopisecké články MeSH
