Hemolysis and eryptosis contribute to anemia encountered in patients undergoing chemotherapy. Eicosapentaenoic acid (EPA) is an omega-3 dietary fatty acid that has anticancer potential by inducing apoptosis in cancer cells, but its effect on the physiology and lifespan of red blood cells (RBCs) is understudied. Human RBCs were exposed to anticancer concentrations of EPA (10-100 ?M) for 24 h at 37 °C. Acetylcholinesterase (AChE) activity and hemolysis were measured by colorimetric assays whereas annexin-V-FITC and forward scatter (FSC) were employed to identify eryptotic cells. Oxidative stress was assessed by H2DCFDA and intracellular Ca2+ was measured by Fluo4/AM. EPA significantly increased hemolysis and K+ leakage, and LDH and AST activities in the supernatants in a concentration-dependent manner. EPA also significantly increased annexin-V-FITC-positive cells and Fluo4 fluorescence and decreased FSC and AChE activity. A significant reduction in the hemolytic activity of EPA was noted in the presence extracellular isosmotic urea, 125 mM KCl, and polyethylene glycol 8000 (PEG 8000), but not sucrose. In conclusion, EPA stimulates hemolysis and eryptosis through Ca2+ buildup and AChE inhibition. Urea, blocking KCl efflux, and PEG 8000 alleviate the hemolytic activity of EPA. The anticancer potential of EPA may be optimized using Ca2+ channel blockers and chelators to minimize its toxicity to off-target tissue. Keywords: EPA, Eryptosis, Hemolysis, Calcium, Anticancer.

• MeSH
• acetylcholinesterasa metabolismus   MeSH
• cholinesterasové inhibitory * farmakologie   MeSH
• eryptóza účinky léků   MeSH
• erytrocytární membrána * účinky léků   metabolismus   MeSH
• erytrocyty účinky léků   metabolismus   MeSH
• fosfatidylseriny * metabolismus   MeSH
• hemolýza * účinky léků   MeSH
• kyselina eikosapentaenová * farmakologie   MeSH
• lidé MeSH
• vápník metabolismus   MeSH
• vápníková signalizace * účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetylcholinesterasa MeSH
• cholinesterasové inhibitory * MeSH
• fosfatidylseriny * MeSH
• kyselina eikosapentaenová * MeSH
• vápník MeSH

The somatostatin (SST) receptor family controls pituitary hormone secretion, but the distribution and specific roles of these receptors on the excitability and voltage-gated calcium signaling of hormone producing pituitary cells have not been fully characterized. Here we show that the rat pituitary gland expressed Sstr1, Sstr2, Sstr3, and Sstr5 receptor genes in a cell type-specific manner: Sstr1 and Sstr2 in thyrotrophs, Sstr3 in gonadotrophs and lactotrophs, Sstr2, Sstr3, and Sstr5 in somatotrophs, and none in corticotrophs and melanotrophs. Most gonadotrophs and thyrotrophs spontaneously fired high-amplitude single action potentials, which were silenced by SST without affecting intracellular calcium concentrations. In contrast, lactotrophs and somatotrophs spontaneously fired low-amplitude plateau-bursting action potentials in conjunction with calcium transients, both of which were silenced by SST. Moreover, SST inhibited GPCR-induced voltage-gated calcium signaling and hormone secretion in all cell types expressing SST receptors, but the inhibition was more pronounced in somatotrophs. The pattern of inhibition of electrical activity and calcium signaling was consistent with both direct and indirect inhibition of voltage-gated calcium channels, the latter being driven by cell type-specific hyperpolarization. These results indicate that the action of SST in somatotrophs is enhanced by the expression of several types of SST receptors and their slow desensitization, that SST may play a role in the electrical resynchronization of gonadotrophs, thyrotrophs, and lactotrophs, and that the lack of SST receptors in corticotrophs and melanotrophs keeps them excitable and ready to responses to stress.

• Klíčová slova
• Gonadotrophs, Lactotrophs, Pituitary, Somatostatin receptors, Somatotrophs, Thyrotrophs, Voltage-gated calcium influx,
• MeSH
• akční potenciály účinky léků   MeSH
• gonadotropní buňky metabolismus   účinky léků   MeSH
• hypofýza * metabolismus   MeSH
• krysa rodu Rattus MeSH
• potkani Wistar MeSH
• receptory somatostatinu * metabolismus   genetika   MeSH
• somatostatin metabolismus   MeSH
• vápník metabolismus   MeSH
• vápníková signalizace * účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• receptory somatostatinu * MeSH
• somatostatin receptor 5 MeSH Prohlížeč
• somatostatin MeSH
• vápník MeSH

Neuronal voltage-gated calcium channels play a pivotal role in the conversion of electrical signals into calcium entry into nerve endings that is required for the release of neurotransmitters. They are under the control of a number of cellular signaling pathways that serve to fine tune synaptic activities, including G-protein coupled receptors (GPCRs) and the opioid system. Besides modulating channel activity via activation of second messengers, GPCRs also physically associate with calcium channels to regulate their function and expression at the plasma membrane. In this mini review, we discuss the mechanisms by which calcium channels are regulated by classical opioid and nociceptin receptors. We highlight the importance of this regulation in the control of neuronal functions and their implication in the development of disease conditions. Finally, we present recent literature concerning the use of novel μ-opioid receptor/nociceptin receptor modulators and discuss their use as potential drug candidates for the treatment of pain.

• Klíčová slova
• G-protein coupled receptors, Mu opioid receptor, Nociception opioid receptor, Voltage-gated calcium channels,
• MeSH
• agonisté vápníkových kanálů farmakologie   MeSH
• blokátory kalciových kanálů farmakologie   MeSH
• lidé MeSH
• neurony účinky léků   fyziologie   MeSH
• opioidní analgetika farmakologie   MeSH
• receptory opiátové agonisté   fyziologie   MeSH
• vápníková signalizace účinky léků   fyziologie   MeSH
• vápníkové kanály fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• agonisté vápníkových kanálů MeSH
• blokátory kalciových kanálů MeSH
• opioidní analgetika MeSH
• receptory opiátové MeSH
• vápníkové kanály MeSH

The effects of ER stress on protein secretion by cardiac myocytes are not well understood. In this study, the ER stressor thapsigargin (TG), which depletes ER calcium, induced death of cultured neonatal rat ventricular myocytes (NRVMs) in high media volume but fostered protection in low media volume. In contrast, another ER stressor, tunicamycin (TM), a protein glycosylation inhibitor, induced NRVM death in all media volumes, suggesting that protective proteins were secreted in response to TG but not TM. Proteomic analyses of TG- and TM-conditioned media showed that the secretion of most proteins was inhibited by TG and TM; however, secretion of several ER-resident proteins, including GRP78 was increased by TG but not TM. Simulated ischemia, which decreases ER/SR calcium also increased secretion of these proteins. Mechanistically, secreted GRP78 was shown to enhance survival of NRVMs by collaborating with a cell-surface protein, CRIPTO, to activate protective AKT signaling and to inhibit death-promoting SMAD2 signaling. Thus, proteins secreted during ER stress mediated by ER calcium depletion can enhance cardiac myocyte viability.

• Klíčová slova
• Cardiac myocyte death, Cardiokine, Cardioprotection, ER stress, Heart failure, Proteostasis,
• MeSH
• apoptóza MeSH
• autokrinní signalizace MeSH
• biologické markery MeSH
• chaperon endoplazmatického retikula BiP MeSH
• epidermální růstový faktor metabolismus   MeSH
• kardiomyocyty účinky léků   metabolismus   MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• membránové glykoproteiny metabolismus   MeSH
• myši MeSH
• náchylnost k nemoci MeSH
• nádorové proteiny metabolismus   MeSH
• parakrinní signalizace MeSH
• proteom * MeSH
• proteomika * metody   MeSH
• sarkoplazmatické retikulum metabolismus   MeSH
• signální transdukce účinky léků   MeSH
• stres endoplazmatického retikula * účinky léků   MeSH
• thapsigargin farmakologie   MeSH
• vápník metabolismus   MeSH
• vápníková signalizace účinky léků   MeSH
• viabilita buněk MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• biologické markery MeSH
• chaperon endoplazmatického retikula BiP MeSH
• epidermální růstový faktor MeSH
• Hspa5 protein, mouse MeSH Prohlížeč
• membránové glykoproteiny MeSH
• nádorové proteiny MeSH
• proteom * MeSH
• Tdgf1 protein, mouse MeSH Prohlížeč
• thapsigargin MeSH
• vápník MeSH

Several papers have reported that calcium channel blocking drugs were associated with increased breast cancer risk and worsened prognosis. One of the most common signs of breast tumors is the presence of small deposits of calcium, known as microcalcifications. Therefore, we studied the effect of dihydropyridine nifedipine on selected calcium transport systems in MDA-MB-231 cells, originating from triple negative breast tumor and JIMT1 cells that represent a model of HER2-positive breast cancer, which possesses amplification of HER2 receptor, but cells do not response to HER2 inhibition treatment with trastuzumab. Also, we compared the effect of nifedipine on colorectal DLD1 and ovarian A2780 cancer cells. Both, inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) and type 1 sodium calcium exchanger (NCX1) were upregulated due to nifedipine in DLD1 and A2780 cells, but not in breast cancer MDA-MB-231 and JIMT1 cells. On contrary to MDA-MB-231 and JIMT1 cells, in DLD1 and A2780 cells nifedipine induced apoptosis in a concentration-dependent manner. After NCX1 silencing and subsequent treatment with nifedipine, proliferation was decreased in MDA-MB-231, increased in DLD1 cells, and not changed in JIMT1 cells. Silencing of IP3R1 revealed increase in proliferation in DLD1 and JIMT1 cells, but caused decrease in proliferation in MDA-MB-231 cell line after nifedipine treatment. Interestingly, after nifedipine treatment migration was not significantly affected in any of tested cell lines after NCX1 silencing. Due to IP3R1 silencing, significant decrease in migration occurred in MDA-MB-231 cells after nifedipine treatment, but not in other tested cells. These results support different function of the NCX1 and IP3R1 in the invasiveness of various cancer cells due to nifedipine treatment.

• Klíčová slova
• Apoptosis, Breast cancer, Inositol 1,4,5-trisphosphate receptor, Migration, Sodium calcium exchanger 1,
• MeSH
• apoptóza účinky léků   genetika   MeSH
• blokátory kalciových kanálů farmakologie   MeSH
• inositol-1,4,5-trisfosfát - receptory genetika   metabolismus   MeSH
• kolorektální nádory genetika   metabolismus   patologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory prsu genetika   metabolismus   patologie   MeSH
• nádory vaječníků genetika   metabolismus   patologie   MeSH
• nifedipin farmakologie   MeSH
• pohyb buněk účinky léků   genetika   MeSH
• proliferace buněk účinky léků   genetika   MeSH
• protinádorové látky imunologicky aktivní farmakologie   MeSH
• pumpa pro výměnu sodíku a vápníku genetika   metabolismus   MeSH
• receptor erbB-2 genetika   metabolismus   MeSH
• regulace genové exprese u nádorů účinky léků   MeSH
• RNA interference MeSH
• trastuzumab farmakologie   MeSH
• triple-negativní karcinom prsu genetika   metabolismus   patologie   MeSH
• vápníková signalizace účinky léků   genetika   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• blokátory kalciových kanálů MeSH
• inositol-1,4,5-trisfosfát - receptory MeSH
• nifedipin MeSH
• protinádorové látky imunologicky aktivní MeSH
• pumpa pro výměnu sodíku a vápníku MeSH
• receptor erbB-2 MeSH
• sodium-calcium exchanger 1 MeSH Prohlížeč
• trastuzumab MeSH

Our studies in hypertensive Ren-2 transgenic rats (TGR) demonstrated that chronic administration of atrasentan (ETA receptor antagonist) decreased blood pressure by reduced Ca2+ influx through L-type voltage-dependent calcium channels (L-VDCC) and attenuated angiotensin II-dependent vasoconstriction. We were interested whether bosentan (nonselective ET(A)/ET(B) receptor antagonist) would have similar effects. Young 4-week-old (preventive study) and adult 8-week-old (therapeutic study) heterozygous TGR and their normotensive Hannover Sprague-Dawley (HanSD) controls were fed normal-salt (NS, 0.6 % NaCl) or high-salt (HS, 2 % NaCl) diet for 8 weeks. An additional group of TGR fed HS was treated with bosentan (100 mg/kg/day). Bosentan had no effect on BP of TGR fed high-salt diet in both the preventive and therapeutic studies. There was no difference in the contribution of angiotensin II-dependent and sympathetic vasoconstriction in bosentan-treated TGR compared to untreated TGR under the condition of high-salt intake. However, bosentan significantly reduced NO-dependent vasodilation and nifedipine-sensitive BP component in TGR on HS diet. A highly important correlation of nifedipine-induced BP change and the BP after L-NAME administration was demonstrated. Although bosentan did not result in any blood pressure lowering effects, it substantially influenced NO-dependent vasodilation and calcium influx through L-VDCC in the heterozygous TGR fed HS diet. A significant correlation of nifedipine-induced BP change and the BP after L-NAME administration suggests an important role of nitric oxide in the closure of L-type voltage dependent calcium channels.

• MeSH
• antagonisté endotelinového receptoru farmakologie   MeSH
• bosentan farmakologie   MeSH
• heterozygot MeSH
• hypertenze farmakoterapie   genetika   metabolismus   patofyziologie   MeSH
• krevní tlak účinky léků   MeSH
• kuchyňská sůl * MeSH
• modely nemocí na zvířatech MeSH
• oxid dusnatý metabolismus   MeSH
• potkani Sprague-Dawley MeSH
• potkani transgenní MeSH
• renin genetika   MeSH
• vápníková signalizace účinky léků   MeSH
• vápníkové kanály - typ L metabolismus   MeSH
• vazodilatace účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antagonisté endotelinového receptoru MeSH
• bosentan MeSH
• kuchyňská sůl * MeSH
• mRen2 protein, rat MeSH Prohlížeč
• oxid dusnatý MeSH
• renin MeSH
• vápníkové kanály - typ L MeSH

Calcium (Ca2+) signaling and the modulation of intracellular calcium ([Ca2+]i) levels play critical roles in several key processes that regulate cellular survival, growth, differentiation, metabolism, and death in normal cells. On the other hand, aberrant Ca2+-signaling and loss of [Ca2+]i homeostasis contributes to tumor initiation proliferation, angiogenesis, and other key processes that support tumor progression in several different cancers. Currently, chemically and functionally distinct drugs are used as chemotherapeutic agents in the treatment and management of cancer among which certain anti-cancer drugs reportedly suppress pro-survival signals and activate pro-apoptotic signaling through modulation of Ca2+-signaling-dependent mechanisms. Most importantly, the modulation of [Ca2+]i levels via the endoplasmic reticulum-mitochondrial axis and corresponding action of channels and pumps within the plasma membrane play an important role in the survival and death of cancer cells. The endoplasmic reticulum-mitochondrial axis is of prime importance when considering Ca2+-signaling-dependent anti-cancer drug targets. This review discusses how calcium signaling is targeted by anti-cancer drugs and highlights the role of calcium signaling in epigenetic modification and the Warburg effect in tumorigenesis.

• Klíčová slova
• Intracellular calcium, anti-cancer drugs, apoptosis, proliferation,
• MeSH
• antitumorózní látky farmakologie   terapeutické užití   MeSH
• apoptóza účinky léků   MeSH
• cílená molekulární terapie metody   MeSH
• endoplazmatické retikulum účinky léků   metabolismus   MeSH
• lidé MeSH
• mitochondrie účinky léků   metabolismus   MeSH
• nádory farmakoterapie   metabolismus   MeSH
• proliferace buněk účinky léků   MeSH
• vápník metabolismus   MeSH
• vápníková signalizace účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antitumorózní látky MeSH
• vápník MeSH

Pioglitazone (PIO) is a thiazolidindione antidiabetic agent which improves insulin sensitivity and reduces blood glucose in experimental animals and treated patients. At the cellular level the actions of PIO in diabetic heart are poorly understood. A previous study has demonstrated shortened action potential duration and inhibition of a variety of transmembrane currents including L-type Ca(2+) current in normal canine ventricular myocytes. The effects of PIO on shortening and calcium transport in ventricular myocytes from the Goto-Kakizaki (GK) type 2 diabetic rat have been investigated. 10 min exposure to PIO (0.1-10 microM) reduced the amplitude of shortening to similar extents in ventricular myocytes from GK and control rats. 1 microM PIO reduced the amplitude of the Ca(2+) transients to similar extents in ventricular myocytes from GK and control rats. Caffeine-induced Ca(2+) release from the sarcoplasmic reticulum and recovery of Ca(2+) transients following application of caffeine and myofilament sensitivity to Ca(2+) were not significantly altered in ventricular myocytes from GK and control rats. Amplitude of L-type Ca(2+) current was not significantly decreased in myocytes from GK compared to control rats and by PIO treatment. The negative inotropic effects of PIO may be attributed to a reduction in the amplitude of the Ca(2+) transient however, the mechanisms remain to be resolved.

• MeSH
• biologický transport účinky léků   MeSH
• diabetes mellitus 2. typu farmakoterapie   patofyziologie   MeSH
• experimentální diabetes mellitus farmakoterapie   patofyziologie   MeSH
• hypoglykemika farmakologie   terapeutické užití   MeSH
• kardiomyocyty účinky léků   fyziologie   MeSH
• kontrakce myokardu účinky léků   fyziologie   MeSH
• krysa rodu Rattus MeSH
• pioglitazon MeSH
• potkani Wistar MeSH
• srdeční komory účinky léků   MeSH
• thiazolidindiony farmakologie   terapeutické užití   MeSH
• vápníková signalizace účinky léků   fyziologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hypoglykemika MeSH
• pioglitazon MeSH
• thiazolidindiony MeSH

Neural rosette formation is a critical morphogenetic process during neural development, whereby neural stem cells are enclosed in rosette niches to equipoise proliferation and differentiation. How neural rosettes form and provide a regulatory micro-environment remains to be elucidated. We employed the human embryonic stem cell-based neural rosette system to investigate the structural development and function of neural rosettes. Our study shows that neural rosette formation consists of five types of morphological change: intercalation, constriction, polarization, elongation and lumen formation. Ca2+ signaling plays a pivotal role in the five steps by regulating the actions of the cytoskeletal complexes, actin, myosin II and tubulin during intercalation, constriction and elongation. These, in turn, control the polarizing elements, ZO-1, PARD3 and β-catenin during polarization and lumen production for neural rosette formation. We further demonstrate that the dismantlement of neural rosettes, mediated by the destruction of cytoskeletal elements, promotes neurogenesis and astrogenesis prematurely, indicating that an intact rosette structure is essential for orderly neural development.

• Klíčová slova
• Adherens junctions, Calcium, Cytoskeleton proteins, Embryonic stem cells, Neural rosette formation, Neural stem cell niche, Neurogenesis,
• MeSH
• aktiny metabolismus   MeSH
• apoptóza účinky léků   MeSH
• buněčný rodokmen účinky léků   MeSH
• cytoskelet účinky léků   metabolismus   MeSH
• lidé MeSH
• lidské embryonální kmenové buňky cytologie   účinky léků   metabolismus   MeSH
• myosin typu II metabolismus   MeSH
• nervové kmenové buňky cytologie   účinky léků   metabolismus   MeSH
• neurogeneze účinky léků   MeSH
• neurony cytologie   účinky léků   metabolismus   ultrastruktura   MeSH
• polarita buněk účinky léků   MeSH
• protein zonula occludens 1 metabolismus   MeSH
• tvar buňky * účinky léků   MeSH
• tvorba rozet * MeSH
• vápník farmakologie   MeSH
• vápníková signalizace * účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aktiny MeSH
• myosin typu II MeSH
• protein zonula occludens 1 MeSH
• vápník MeSH

In ischemic/reperfusion (I/R) injured hearts, severe oxidative stress occurs and is associated with intracellular calcium (Ca(2+)) overload. Glucagon-Like Peptide-1 (GLP-1) analogues have been shown to exert cardioprotection in I/R heart. However, there is little information regarding the effects of GLP-1 analogue on the intracellular Ca(2+) regulation in the presence of oxidative stress. Therefore, we investigated the effects of GLP-1 analogue, (liraglutide, 10 microM) applied before or after hydrogen peroxide (H(2)O(2), 50 microM) treatment on intracellular Ca(2+) regulation in isolated cardiomyocytes. We hypothesized that liraglutide can attenuate intracellular Ca(2+) overload in cardiomyocytes under H(2)O(2)-induced cardiomyocyte injury. Cardiomyocytes were isolated from the hearts of male Wistar rats. Isolated cardiomyocytes were loaded with Fura-2/AM and fluorescence intensity was recorded. Intracellular Ca(2+) transient decay rate, intracellular Ca(2+) transient amplitude and intracellular diastolic Ca(2+) levels were recorded before and after treatment with liraglutide. In H(2)O(2) induced severe oxidative stressed cardiomyocytes (which mimic cardiac I/R) injury, liraglutide given prior to or after H(2)O(2) administration effectively increased both intracellular Ca(2+) transient amplitude and intracellular Ca(2+) transient decay rate, without altering the intracellular diastolic Ca(2+) level. Liraglutide attenuated intracellular Ca(2+) overload in H(2)O(2)-induced cardiomyocyte injury and may be responsible for cardioprotection during cardiac I/R injury by preserving physiological levels of calcium handling during the systolic and diastolic phases of myocyte activation.

• MeSH
• hypoglykemika farmakologie   MeSH
• intracelulární tekutina účinky léků   metabolismus   MeSH
• kardiomyocyty účinky léků   metabolismus   MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• liraglutid farmakologie   MeSH
• oxidační stres účinky léků   fyziologie   MeSH
• peroxid vodíku toxicita   MeSH
• potkani Wistar MeSH
• vápníková signalizace účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hypoglykemika MeSH
• liraglutid MeSH
• peroxid vodíku MeSH