151 research outputs found
Targeting the sarcolemmal calcium pump: a potential novel strategy for the treatment of cardiovascular disease.
No full textpeer reviewedIntracellular calcium dynamics play a very important role in mediating contraction and signalling in cardiomyocytes and vascular smooth muscle cells. A number of calcium transporters have been identified that orchestrate a complex process of excitation-contraction coupling and molecular signalling. Despite the variability of the calcium transporters expressed in cardiomyocytes, most calcium channel blockers used therapeutically target the L-type calcium channel and exhibit antihypertensive and/or vasodilating activities. Recently, another calcium pump which is located in the sarcolemma has been shown to mediate cardiac contractility and vascular tone. Interestingly, this sarcolemmal calcium pump (also known as Plasma Membrane Calcium/calmodulin dependent ATPase or PMCA) exerts its function not by altering global calcium concentration, but by mediating signal transduction pathways. This review will discuss recent advances that support the key roles of PMCA as signalling molecule and the potential to target this calcium pump as a novel approach for the treatment of cardiovascular disease
The Control of Sub-plasma Membrane Calcium Signalling by the Plasma Membrane Calcium ATPase Pump PMCA4
No full textGenetic and Pharmacological YAP Activation Induces Proliferation and Improves Survival in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
No full textCardiomyocyte loss following myocardial infarction cannot be addressed with current clinical therapies. Cell therapy with induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is a potential approach to replace cardiomyocyte loss. However, engraftment rates in pre-clinical studies have been low, highlighting a need to refine current iPSC-CM technology. In this study, we demonstrated that inducing Yes-associated protein (YAP) by genetic and pharmacological approaches resulted in increased iPSC-CM proliferation and reduced apoptosis in response to oxidative stress. Interestingly, iPSC-CM maturation was differently affected by each strategy, with genetic activation of YAP resulting in a more immature cardiomyocyte-like phenotype not witnessed upon pharmacological YAP activation. Overall, we conclude that YAP activation in iPSC-CMs enhances cell survival and proliferative capacity. Therefore, strategies targeting YAP, or its upstream regulator the Hippo signalling pathway, could potentially be used to improve the efficacy of iPSC-CM technology for use as a future regenerative therapy in myocardial infarction
Physiological implications of the interaction between the plasma membrane calcium pump and nNOS.
No full textpeer reviewedThe tight regulation of intracellular calcium levels is essential for the normal function of a great many cellular processes, and disruption of this regulation, resulting in sustained increases in intracellular-free calcium, has been associated with numerous diseases. One of the several transporters involved in calcium homeostasis is a P-type ATPase known as the plasma membrane calcium/calmodulin-dependent ATPase (PMCA) which is involved in calcium extrusion from the cytosol to the extracellular compartment. It has long been established that in many cell types, in particular non-excitable cells, the primary role of PMCA is in the bulk transport of intracellular calcium; however, its role in excitable cells is less clear. In the heart, for example, calcium is essential for contractile function as well as being a key messenger in signal transduction pathways; however, the mechanisms by which the cardiomyocyte distinguishes between these roles of calcium remain unclear. It is perhaps the transporters not involved in the contractile cycle (such as PMCA) that are able to carry non-contractile signals. This review will highlight the role of PMCA as a modulator of signal transduction pathways and in particular the role of isoform 4 in the regulation of the nitric oxide signalling pathway
Ras-association domain family member 1A (RASSF1A)-where the heart and cancer meet.
No full textpeer reviewedThe close relationship between signaling pathways regulating tumor growth and cardiac hypertrophy has attracted considerable interest. Although the involvement of proto-oncogenes in positively modulating myocardial hypertrophy has long been recognized, little is known about factors that counterregulate them. In this article, we review the novel tumor suppressor Ras-association domain family protein isoform 1A (RASSF1A), which strongly inhibits the prohypertrophic Ras-Raf1-ERK1/2 pathway in the heart. RASSF1A interacts with a number of important signaling molecules regulating cell growth, survival, and apoptosis; therefore, it serves as a key adaptor molecule that integrates the upstream stimuli and transduces them to the selective downstream effectors
Kelainan Peak Expiratory Flow Rate Dibandingkan dengan Keluhan Sistim Pernapasan – studi pada 75 anggota pasukan kuning, Surabaya
Full text linkTelah dilakukan kajian untuk membandingkan hasil pemeriksaan faal paru Peak Expiratory Flow Rate (PEFR) dalam mendeteksi kelainan paru obstruktif dengan anamnesis adanya keluhan batuk, pengeluaran dahak, sesak nafas dan nafas berbunyi. Sebagai subyek penelitian adalah anggota pasukan kuning Kotamadya Surabaya yang bertugas di jalan raya sebanyak 75 orang. Dipilih anggota pasukan kuning karena dalam melaksanakan tugas sehari-hari diduga mendapat pemaparan polusi debu dan gas buang kendaraan bermotor. Hasil yang didapat adalah proporsi kelainan PEFR secara keseluruhan sebesar 42,67%, di antara yang mengeluh keluhan batuk sebesar 24,00%, di antara yang mengeluarkan dahak sebesar 14,67%, di antara yang sesak nafas sebesar 22,67% dan di antara yang nafasnya berbunyi sebesar 10,67%.
Ternyata didapatkan hubungan antara kelainan faal paru PEFR dengan adanya keluhan batuk (p = 0,0216), dengan keluhan pengeluaran dahak (p = 0,0005), dengan keluhan sesak nafas (p = 0,018) dan dengan keluhan nafas berbunyi (p = 0,0000). Subyek dengan kelainan faal paru PEFR tanpa keluhan berkisar antara 30,67 –36% dari seluruh subyek yang diperiksa
Plasma membrane calcium ATPase and its relationship to nitric oxide signaling in the heart.
No full textpeer reviewedThe plasma membrane calcium/calmodulin-dependent ATPase (PMCA) is a ubiquitously expressed calcium-extruding enzymatic pump. In the majority of cells the main function of PMCA is as the only system to extrude calcium from the cytosol, however, in the excitable cells of the heart it has only a minor role in the bulk removal of calcium compared to the sodium-calcium exchanger. There is increasing evidence to suggest that PMCA has an additional role as a potential modulator of a number of signal transduction pathways. Of key interest in the heart is the functional interaction between the calcium/calmodulin-dependent enzyme neuronal nitric oxide synthase (nNOS) and isoform 4 of PMCA. Nitric oxide production from nNOS is known to be important in the regulation of excitation-contraction (EC) coupling and subsequently contractility. This article will focus on recent evidence suggesting that PMCA4 has a regulatory role in the nitric oxide signaling pathway in the heart
Ca2+ signalling in cardiovascular disease: the role of the plasma membrane calcium pumps.
Full text linkpeer reviewedThe plasma membrane calcium ATPases (PMCA) are a family of genes which extrude Ca(2+) from the cell and are involved in the maintenance of intracellular free calcium levels and/or with Ca(2+) signalling, depending on the cell type. In the cardiovascular system, Ca(2+) is not only essential for contraction and relaxation but also has a vital role as a second messenger in signal transduction pathways. A complex array of mechanisms regulate intracellular free calcium levels in the heart and vasculature and a failure in these systems to maintain normal Ca(2+) homeostasis has been linked to both heart failure and hypertension. This article focuses on the functions of PMCA, in particular isoform 4 (PMCA4), in the heart and vasculature and the reported links between PMCAs and contractile function, cardiac hypertrophy, cardiac rhythm and sudden cardiac death, and blood pressure control and hypertension. It is becoming clear that this family of calcium extrusion pumps have essential roles in both cardiovascular health and disease
Calcium signaling dysfunction in heart disease.
No full textpeer reviewedIn the heart, Ca(2+) is crucial for the regulation of contraction and intracellular signaling, processes, which are vital to the functioning of the healthy heart. Ca(2+) -activated signaling pathways must function against a background of large, rapid, and tightly regulated changes in intracellular free Ca(2+) concentrations during each contraction and relaxation cycle. This review highlights a number of proteins that regulate signaling Ca(2+) in both normal and pathological conditions including cardiac hypertrophy and heart failure, and discusses how these pathways are not regulated by the marked elevation in free intracellular calcium ([Ca(2+) ](i)) during contraction but require smaller sustained increases in Ca(2+) concentration. In addition, we present published evidence that the pool of Ca(2+) that regulates signaling is compartmentalized into distinct cellular microdomains and is thus distinct from that regulating contraction
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