Generation and role of calcium signal in adrenal glomerulosa cells

This work was supported by the Ministerio de Educación y Ciencia (project grant SAF 2005-00385) (Madrid, Spain), Ministerio de Sanidad y Consumo (project grant PIO60021) (Madrid, Spain) Numerous steatotic livers are discarded as unsuitable for transplantation because of their poor tolerance of ischemia-reperfusion(I/R). The injurious effects of angiotensin (Ang)-II and the benefits of Ang-(1-7) in various pathologies are well documented. We examined the generation of Ang II and Ang-(1-7) in steatotic and nonsteatotic liver grafts from Zucker rats following transplantation. We also studied in both liver grafts the effects of Ang-II receptors antagonists and Ang-(1-7) receptor antagonists on hepatic I/R damage associated with transplantation. Nonsteatotic grafts showed higher Ang II levels than steatotic grafts, whereas steatotic grafts showed higher Ang-(1-7) levels than nonsteatotic grafts. Ang II receptor antagonists protected only nonsteatotic grafts against damage, whereas Ang-(1-7) receptor antagonists were effective only in steatotic grafts. The protection conferred by Ang II receptor antagonists in nonsteatotic grafts was associated with ERK 1/2 overexpression, whereas the beneficial effects of Ang-(1-7) receptor antagonists in steatotic grafts may be mediated by NO inhibition. Our results show that Ang II receptor antagonists are effective only in nonsteatotic liver transplantation and point to a novel therapeutic target in liver transplantation based on Ang-(1-7), which is specific for steatotic liver grafts.

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“…(35,36). Toshimitsu So and colleagues reported that AT1R antagonist ameliorated vasoconstriction in myocardial I/R (37).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Targets in Liver Transplantation: Angiotensin II in Nonsteatotic Grafts and Angiotensin-(1—7) in Steatotic Grafts

Alfany-Fernandez

Casillas-Ramírez

Bintanel-Morcillo

et al. 2009

American Journal of Transplantation

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“…cells [6,36] or to prostaglandin F 2␣ in rat luteal cells [25] stimulates the reduction of mitochondrial pyridine nucleotides. The Ca 2; signal, evoked by the Ca 2; mobilizing agonists, is brought about by IP 3 -induced Ca 2; release [37] as well as by store-operated (capacitative) Ca 2; influx [25,38]. The mitochondrial Ca 2; signal and the ensuing activation of Ca 2; -dependent mitochondrial dehydrogenases [2] during the action of IP 3 may be accounted for by the transfer of the Ca 2; signal from the transiently formed high-Ca 2; microdomains between the IP 3 receptors and the vicinal mitochondria into the mitochondrial matrix [8,39].…”

Section: Effect Of Elevated Extramitochondrial [Ca 2; ; ] On Mitochonmentioning

confidence: 99%

Mitochondria respond to Ca2+ already in the submicromolar range: correlation with redox state

et al. 2002

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'The renaissance of mitochondrial calcium transport', the title of a recently published review [1], appropriately characterizes the current interest in the role of mitochondria played in the control of intracellular calcium metabolism. It was beleived that mitochondria sequester Ca 2; in case of calcium intoxication but have no role in the physiological control of calcium metabolism. This view was first challenged by the description of Ca 2; -sensitive mitochondrial dehydrogenases [2]. Thereafter, in the last decade it was revealed that cytoplasmic Summary Rapid formation of high-Ca 2; perimitochondrial cytoplasmic microdomains has been shown to evoke mitochondrial Ca 2; signal and activate mitochondrial dehydrogenases, however, the significance of submicromolar cytoplasmic Ca 2; concentrations in the control of mitochondrial metabolism has not been sufficiently elucidated. Here we studied the mitochondrial response to application of Ca 2; at buffered concentrations in permeabilized rat adrenal glomerulosa cells, in an insulin-producing cell line (INS-1/EK-3) and in an osteosarcoma cell line (143BmA-13). Mitochondrial Ca 2; concentration was measured with the fluorescent dye rhod-2 and, using an in situ calibration method, with the mitochondrially targeted luminescent protein mt-aequorin. In both endocrine cell types, mitochondrial Ca 2; concentration increased in response to elevated cytoplasmic Ca 2; concentration (between 60 and 740 nM) and an increase in mitochondrial Ca 2; concentration could be revealed already at a cytoplasmic Ca 2; concentration step from 60-140 nM. Similar responses were observed in the osteosarcoma cell line, although a clearcut response was first observed at 280 nM extramitochondrial Ca 2; only. As examined in glomerulosa cells, graded increases in cytoplasmic Ca 2; concentration were associated with graded increases in the reduction of mitochondrial pyridine nucleotides, consistent with Ca 2; -dependent activation of mitochondrial dehydrogenases. Our data indicate that in addition to the recognized role of high-Ca 2; cytoplasmic microdomains, also small Ca 2; signals may influence mitochondrial metabolism.

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“…Next, we examined the functional significance of D1R-AT1R interaction. AT1R are known to couple to Gq proteins, and activation of AT1R triggers activation of PLC, generation of inositol 1,4,5-trisphosphate (IP 3 ), activation of the IP 3 receptor (IP3R), and, as a result, release of calcium from the intracellular stores (11,20,22). RPT cells were loaded with the calcium-sensitive dye fura 2, and ratiometric recordings of intracellular calcium were carried out.…”

Section: D1r-at1r Interaction Is Modulated By Receptor-activating Ligmentioning

confidence: 99%

Negative reciprocity between angiotensin II type 1 and dopamine D1 receptors in rat renal proximal tubule cells

Khan

Špicarová²,

Zelenin³

et al. 2008

American Journal of Physiology-Renal Physiology

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Sodium excretion is bidirectionally regulated by dopamine, acting on D1-like receptors (D1R) and angiotensin II, acting on AT1 receptors (AT1R). Since sodium excretion has to be regulated with great precision within a short frame of time, we tested the short-term effects of agonist binding on the function of the reciprocal receptor within the D1R-AT1R complex in renal proximal tubule cells. Exposure of rat renal proximal tubule cells to a D1 agonist was found to result in a rapid partial internalization of AT1R and complete abolishment of AT1R signaling. Similarly, exposure of rat proximal tubule cells and renal tissue to angiotensin II resulted in a rapid partial internalization of D1R and abolishment of D1R signaling. D1R and AT1R were, by use of coimmunoprecipitation studies and glutathione-S-transferase pull-down assays, shown to be partners in a multiprotein complex. Na ϩ -K ϩ -ATPase, the target for both receptors, was included in this complex, and a region in the COOH-terminal tail of D1R (residues 397-416) was found to interact with both AT1R and Na ϩ -K ϩ -ATPase. Results indicate that AT1R and D1R function as a unit of opposites, which should provide a highly versatile and sensitive system for short-term regulation of sodium excretion.AT 1 receptors; Na ϩ -K ϩ -ATPase; calcium signaling RENAL SODIUM EXCRETION IS bidirectionally regulated by angiotensin II (ANG II) and dopamine (13). Long-term dopamine exposure is known to decrease AT 1 receptors (AT1R) in renal proximal tubular cells (7). Furthermore, studies by Zeng et al. (21) have shown that long-term stimulation of AT1R results in an upregulation of D1-like receptors (D1R). This effect was not observed in spontaneously hypertensive rats, indicating that the interaction between AT1R and D1R has an impact on blood pressure regulation. Since sodium excretion must be regulated with great precision over a short period of time, it is important that control mechanisms are able to exert their effects within a short time frame. The aim of the current study has been to explore the short-term effects of ANG II exposure on D1R and the short-term effects of a D1-agonist on AT1R. Our approach has been to test the hypothesis that AT1R and D1R form a heteromeric signaling complex, where activation of either receptor may cause internalization and/or interruption of the signaling capacity of the other.The studies were performed using rat proximal tubule cells, since these cells express both AT1R and D1R in both the apical and the basolateral membrane (12,18). Previous studies from our laboratory have shown that in these cells Na ϩ -K ϩ -ATPase, the enzyme responsible for active sodium transport, is bidirectionally regulated by ANG II and dopamine (2). MATERIALS AND METHODS Cells and tissue.All studies were performed using outer cortical tissue from young (3-5 wk) male Sprague-Dawley rats. Immediately after the animals were killed, 250-m slices were taken from the outer renal cortex using a microtome. The outer 250-m region of the rat renal cortex contains Ͼ90% proxi...

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Generation and role of calcium signal in adrenal glomerulosa cells

Cited by 84 publications

References 97 publications

Therapeutic Targets in Liver Transplantation: Angiotensin II in Nonsteatotic Grafts and Angiotensin-(1—7) in Steatotic Grafts

Therapeutic Targets in Liver Transplantation: Angiotensin II in Nonsteatotic Grafts and Angiotensin-(1—7) in Steatotic Grafts

Mitochondria respond to Ca2+ already in the submicromolar range: correlation with redox state

Negative reciprocity between angiotensin II type 1 and dopamine D1 receptors in rat renal proximal tubule cells

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