Reactive oxygen species are an important element of redox regulation in cells and tissues. During physiological processes, molecules undergo chemical changes caused by reduction and oxidation reactions. Free radicals are involved in interactions with other molecules, leading to oxidative stress. Oxidative stress works two ways depending on the levels of oxidizing agents and products. Excessive action of oxidizing agents damages biomolecules, while a moderate physiological level of oxidative stress (oxidative eustress) is necessary to control life processes through redox signaling required for normal cellular operation. High levels of reactive oxygen species (ROS) mediate pathological changes. Oxidative stress helps to regulate cellular phenotypes in physiological and pathological conditions. Nrf2 (nuclear factor erythroid 2-related factor 2, NFE2L2) transcription factor functions as a target nuclear receptor against oxidative stress and is a key factor in redox regulation in hypertension and cardiovascular disease. Nrf2 mediates transcriptional regulation of a variety of target genes. The Keap1-Nrf2-ARE system regulates many detoxification and antioxidant enzymes in cells after the exposure to reactive oxygen species and electrophiles. Activation of Nrf2/ARE signaling is differentially regulated during acute and chronic stress. Keap1 normally maintains Nrf2 in the cytosol and stimulates its degradation through ubiquitination. During acute oxidative stress, oxidized molecules modify the interaction of Nrf2 and Keap1, when Nrf2 is released from the cytoplasm into the nucleus where it binds to the antioxidant response element (ARE). This triggers the expression of antioxidant and detoxification genes. The consequence of long-term chronic oxidative stress is activation of glycogen synthase kinase 3beta (GSK-3beta) inhibiting Nrf2 activity and function. PPARgamma (peroxisome proliferator-activated receptor gamma) is a nuclear receptor playing an important role in the management of cardiovascular diseases, hypertension and metabolic syndrome. PPARgamma targeting of genes with peroxisome proliferator response element (PPRE) has led to the identification of several genes involved in lipid metabolism or oxidative stress. PPARgamma stimulation is triggered by endogenous and exogenous ligands - agonists and it is involved in the activation of several cellular signaling pathways involved in oxidative stress response, such as the PI3K/Akt/NOS pathway. Nrf2 and PPARgamma are linked together with their several activators and Nrf2/ARE and PPARgamma/PPRE pathways can control several types of diseases.
- MeSH
- antioxidační responzivní elementy MeSH
- faktor 2 související s NF-E2 metabolismus MeSH
- hypertenze metabolismus patofyziologie MeSH
- kardiovaskulární nemoci metabolismus patofyziologie MeSH
- KEAP-1 metabolismus MeSH
- krevní tlak * MeSH
- lidé MeSH
- oxidační stres * MeSH
- PPAR gama metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- signální transdukce MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- faktor 2 související s NF-E2 MeSH
- KEAP-1 MeSH
- PPAR gama MeSH
- reaktivní formy kyslíku MeSH
The peroxisome proliferator-activated receptors (PPAR) belong to the nuclear superfamily of ligand-activated transcription factors. PPARgamma acts as a nutrient sensor that regulates several homeostatic functions. Its disruption can lead to vascular pathologies, disorders of fatty acid/lipid metabolism and insulin resistance. PPARgamma can modulate several signaling pathways connected with blood pressure regulation. Firstly, it affects the insulin signaling pathway and endothelial dysfunction by modulation of expression and/or phosphorylation of signaling molecules through the PI3K/Akt/eNOS or MAPK/ET-1 pathways. Secondly, it can modulate gene expression of the renin- angiotensin system - cascade proteins, which potentially slow down the progression of atherosclerosis and hypertension. Thirdly, it can modulate oxidative stress response either directly through PPAR or indirectly through Nrf2 activation. In this context, activation and functioning of PPARgamma is very important in the regulation of several disorders such as diabetes mellitus, hypertension and/or metabolic syndrome.
- MeSH
- buněčný převod mechanických signálů MeSH
- hypertenze patofyziologie MeSH
- inzulin metabolismus MeSH
- krevní tlak * MeSH
- lidé MeSH
- modely kardiovaskulární MeSH
- oxid dusnatý metabolismus MeSH
- oxidační stres MeSH
- PPAR gama metabolismus MeSH
- renin-angiotensin systém * MeSH
- signální transdukce MeSH
- vazodilatace MeSH
- vazokonstrikce MeSH
- vazomotorický systém patofyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- inzulin MeSH
- oxid dusnatý MeSH
- PPAR gama MeSH
The oxidative stress plays an important role in the development of cardiovascular diseases (CVD). In CVD progression an aberrant redox regulation was observed. In this regulation levels of reactive oxygen species (ROS) play an important role in cellular signaling, where Nrf2 is the key regulator of redox homeostasis. Keap1-Nrf2-ARE system regulates a great set of detoxificant and antioxidant enzymes in cells after ROS and electrophiles exposure. In this review we focus on radical-generating systems in cardiovascular system as well as on Nrf2 as a target against oxidative stress and a key player of redox regulation in cardiovascular diseases. We also summarize the current knowledge about the role of Nrf2 in pathophysiology of several CVD (hypertension, cardiac hypertrophy, cardiomyopathies) as well as in cardioprotection against myocardial ischemia/ reperfusion injury.
- MeSH
- antioxidační responzivní elementy * MeSH
- faktor 2 související s NF-E2 metabolismus MeSH
- kardiovaskulární nemoci metabolismus MeSH
- lidé MeSH
- oxidační stres * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- faktor 2 související s NF-E2 MeSH
- NFE2L2 protein, human MeSH Prohlížeč
Mechanisms underlying atrial fibrillation (AF), the most common cardiac arrhythmia, particularly in aged population, are not fully elucidated. We have previously shown an increased propensity of old guinea pigs (GPs) heart to inducible AF when comparing to young animals. This study aimed to verify our hypothesis that susceptibility of aged heart to AF may be attributed to abnormalities in myocardial connexin-43 (Cx43) and extracellular matrix that affect cardiac electrical properties. Experiments were conducted on male and female 4-week-old and 24-week-old GPs. Atrial tissue was processed for analysis of Cx43 topology using immunohistochemistry, expression of Cx43 protein using immunobloting, and expression of mRNA of Cx43 and extracellular matrix metalloproteinase-2 (MMP-2) using real time PCR. Immunohistochemistry revealed uniform Cx43 distribution predominantly on lateral sides of the cardiomyocytes of young male and female GP atria. In contrast, non-uniform distribution, mislocalization and reduced immunolabeling of Cx43 were detected in atria of old GPs. In parallel, the atrial tissue levels of Cx43 mRNA were significantly decreased, while mRNA expression of MMP-2 was significantly increased in old versus young GPs. The changes were more pronounced in old GPs males comparing to females. Findings indicate that age-related down-regulation of atrial Cx43 and up-regulation of MMP-2 as well as disordered Cx43 distribution can facilitate development of AF in old guinea pig hearts.
- MeSH
- down regulace MeSH
- fibrilace síní etiologie metabolismus MeSH
- konexin 43 metabolismus MeSH
- matrixová metaloproteinasa 2 metabolismus MeSH
- morčata MeSH
- myokard metabolismus ultrastruktura MeSH
- stárnutí metabolismus MeSH
- upregulace MeSH
- zvířata MeSH
- Check Tag
- morčata MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- konexin 43 MeSH
- matrixová metaloproteinasa 2 MeSH
The present survey summarizes the data about the structure, function and methods of investigation of the natural substance alpha-lipoic acid. This compound is an important growth factor of many microorganisms and at the same time a disulfide cofactor of dehydrogenases in oxidative phosphorylation. It is a physiological constituent of biological membranes, an efficient antioxidant and a scavenger of free radicals. Lipoic acid possesses anticarcinogenic and preventive effects which protect the calls from damage.
- MeSH
- antioxidancia * chemie farmakologie MeSH
- kyselina lipoová * chemie farmakologie MeSH
- lidé MeSH
- nádorové buňky kultivované účinky léků MeSH
- protinádorové látky * chemie farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- antioxidancia * MeSH
- kyselina lipoová * MeSH
- protinádorové látky * MeSH
Calmodulin (CaM) interactions with bilayer lipid membranes (BLM) were studied by measuring modulus of elasticity in direction perpendicular to the membrane plane (E perpendicular) and intramembrane potential delta psi. Upon interaction of CaM with egg phosphatidylcholine and asolectin BLM the parameter E perpendicular grew slightly (not more than by 10% as compared to the respective vale for nonmodified BLM), suggesting a weak effect on the ordering of the hydrophobic moiety of the lipid bilayer. In the presence of mesocaine (Mes), a calmodulin inhibitor, CaM affected the incorporation of Mes into the membrane. It can be concluded that CaM affects the ordering of the polar (superficial) membrane region.
- MeSH
- acetanilidy * MeSH
- elektrolyty MeSH
- fosfatidylcholiny * MeSH
- fosfolipidy * MeSH
- kalmodulin * MeSH
- kinetika MeSH
- lipidové dvojvrstvy * MeSH
- membránové potenciály MeSH
- pružnost MeSH
- trimekain * MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- acetanilidy * MeSH
- asolectin MeSH Prohlížeč
- elektrolyty MeSH
- fosfatidylcholiny * MeSH
- fosfolipidy * MeSH
- kalmodulin * MeSH
- lipidové dvojvrstvy * MeSH
- trimekain * MeSH
