Search

Producción Científica, Intracellular Ca2+ plays a pivotal role in the control of a large series of cell functions in all types of cells, from neurotransmitter release and muscle contraction to gene expression, cell proliferation and cell death. Ca2+ is transported through specific channels and transporters in the plasma membrane and subcellular organelles such as the endoplasmic reticulum and mitochondria. Therefore, dysregulation of intracellular Ca2+ homeostasis may lead to cell dysfunction and disease. Accordingly, chemical compounds from natural origin and/or synthesis targeting directly or indirectly these channels and proteins may be of interest for the treatment of cell dysfunction and disease. In this review, we show an overview of a group of marine drugs that, from the structural point of view, contain one or various heterocyclic units in their core structure, and from the biological side, they have a direct influence on the transport of calcium in the cell. The marine compounds covered in this review are divided into three groups, which correspond with their direct biological activity, such as compounds with a direct influence in the calcium channel, compounds with a direct effect on the cytoskeleton and drugs with an effect on cancer cell proliferation. For each target, we describe its bioactive properties and synthetic approaches. The wide variety of chemical structures compiled in this review and their significant medical properties may attract the attention of many different researchers., Ministerio de Ciencia e Innovación - (grant RTI2018-099298-B-100), Junta de Castilla y León - (grant VA294-P18)

Cellular Ca 2+signaling results from a complex interplay among a variety of Ca 2+ fluxes going across the plasma membrane and across the membranes of several organelles, together with the buffering effect of large numbers of Ca 2+-binding sites distributed along the cell architecture. Endoplasmic and sarcoplasmic reticulum, mitochondria and even nucleus have all been involved in cellular Ca 2+ signaling, and the mechanisms for Ca 2+ uptake and release from these organelles are well known. In neuroendocrine cells, the secretory granules also constitute a very important Ca 2+-storing organelle, and the possible role of the stored Ca 2+ as a trigger for secretion has attracted considerable attention. However, this possibility is frequently overlooked, and the main reason for that is that there is still considerable uncertainty on the main questions related with granular Ca 2+ dynamics, e.g., the free granular [Ca 2+], the physical state of the stored Ca 2+ or the mechanisms for Ca 2+ accumulation and release from the granules. This review will give a critical overview of the present state of knowledge and the main conflicting points on secretory granule Ca 2+ homeostasis in neuroendocrine cells. © 2011 Elsevier Ltd., This work was supported by grants from Ministerio de Educación y Ciencia (BFU2008-01871) and from Junta de Castilla y León (GR105).

Copyright © by Blackwell Publishing Ltd.-- The definitive version is available at www.blackwell-synergy.com, The recent availability of activators of the mitochondrial Ca2+ uniporter allows direct testing of the influence of mitochondrial Ca2+ uptake on the overall Ca2+ homeostasis of the cell. We show here that activation of mitochondrial Ca2+ uptake by 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) or kaempferol stimulates histamine-induced Ca2+ release from the endoplasmic reticulum (ER) and that this effect is enhanced if the mitochondrial Na+–Ca2+ exchanger is simultaneously inhibited with CGP37157. This suggests that both Ca2+ uptake and release from mitochondria control the ability of local Ca2+ microdomains to produce feedback inhibition of inositol 1,4,5-trisphosphate receptors (InsP3Rs). In addition, the ability of mitochondria to control Ca2+ release from the ER allows them to modulate cytosolic Ca2+ oscillations. In histamine stimulated HeLa cells and human fibroblasts, both PPT and kaempferol initially stimulated and later inhibited oscillations, although kaempferol usually induced a more prolonged period of stimulation. Both compounds were also able to induce the generation of Ca2+ oscillations in previously silent fibroblasts. Our data suggest that cytosolic Ca2+ oscillations are exquisitely sensitive to the rates of mitochondrial Ca2+ uptake and release, which precisely control the size of the local Ca2+ microdomains around InsP3Rs and thus the ability to produce feedback activation or inhibition of Ca2+ release., This work was supported by grants from Ministerio de Educación y Ciencia (BFU2005-05464), from Junta de Castilla y León (VA016A05) and from Fondo de Investigaciones Sanitarias (PI040789). J.S. and E.H.-S. hold research personnel training (FPI) and University personnel training (FPU) fellowships, respectively, from the Spanish Ministerio de Educación y Ciencia. L.V. holds a fellowship from Fondo de Investigaciones Sanitarias (Spanish Ministerio de Sanidad).