Deoxycholic acid activates protein kinase C and phospholipase C via increased Ca2+ entry at plasma membrane

Lau, Bonnie; Colella, Matilde; Ruder, Warren C.; Ranieri, Marianna; Curci, Silvana; Hofer, Aldebaran M.

doi:10.1053/j.gastro.2004.12.046

Cited by 48 publications

(36 citation statements)

References 51 publications

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“…1D). Although not well-characterized, induction of such a pathway by stimuli that induce Ca 2+ influx across the plasma membrane is not without precedence (41,42). Definitive demonstration of the role of this pathway requires genetic models, but pharmacological inhibitors are commonly used in the field of Ca 2+ signaling because of redundancy in regulation (i.e., multiple PLCs) or, conversely, lethality of cells and mice lacking critical regulators (i.e., IP 3 R1).…”

Section: Discussionmentioning

confidence: 99%

Critical role for calcium mobilization in activation of the NLRP3 inflammasome

Murakami

Öckinger

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The NLRP3 (nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3) inflammasome mediates production of inflammatory mediators, such as IL-1β and IL-18, and as such is implicated in a variety of inflammatory processes, including infection, sepsis, autoinflammatory diseases, and metabolic diseases. The proximal steps in NLRP3 inflammasome activation are not well understood. Here we elucidate a critical role for Ca 2+ mobilization in activation of the NLRP3 inflammasome by multiple stimuli. We demonstrate that blocking Ca 2+ mobilization inhibits assembly and activation of the NLRP3 inflammasome complex, and that during ATP stimulation Ca 2+ signaling is pivotal in promoting mitochondrial damage. C/EPB homologous protein, a transcription factor that can modulate Ca 2+ release from the endoplasmic reticulum, amplifies NLRP3 inflammasome activation, thus linking endoplasmic reticulum stress to activation of the NLRP3 inflammasome. Our findings support a model for NLRP3 inflammasome activation by Ca 2+ -mediated mitochondrial damage.innate immunity | mitochondria

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Section: Discussionmentioning

confidence: 99%

Critical role for calcium mobilization in activation of the NLRP3 inflammasome

Murakami

Öckinger

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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753

620

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“…We have shown that the presence of NaTC in the solution containing freshly excysted sporozoites increased the soluble protein content, which may be due to enhanced apical organelle discharge. Apical organelle discharge of C. parvum is calcium dependent (6), and the induction of calcium signaling by bile salts has been well-documented in mammalian cells (7,13,25). Whether or not bile salts induce calcium signaling in C. parvum or other Apicomplexa remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Bile Acids Enhance Invasiveness of Cryptosporidium spp. into Cultured Cells

et al. 2006

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Bile salts such as sodium taurocholate (NaTC) are routinely used to induce the excystation of Cryptosporidium oocysts. Here we show that NaTC significantly enhanced the invasion of several cultured cell lines by freshly excysted Cryptosporidium parvum and Cryptosporidium hominis sporozoites. A variety of purified bile salts or total bile from bovine also enhanced the invasion of cultured cells by C. parvum. Further studies demonstrated that NaTC increased protein secretion and gliding motility of sporozoites, the key processes for successful invasion. These observations may lead to improved Cryptosporidium infectivity of cultured cells and help future studies on the host-parasite interaction.As members of the phylum Apicomplexa, the enteric protozoa Cryptosporidium species share a common apical secreting apparatus that mediates locomotion during cellular invasion (5, 21). Cryptosporidium hominis and Cryptosporidium parvum, whose genomes were sequenced recently (1, 28), are the species most frequently linked with human cryptosporidiosis (21,27). Infection begins with the oral uptake of Cryptosporidium oocysts, the environmentally resistant form, which then pass through the acidic stomach before entering the small intestine, where they presumably excyst. Although the molecular and biochemical mechanisms involved in excystation are poorly understood, it is believed that host environmental factors, such as temperature, pH, proteases, bile salts, and possibly other unknown factors, trigger the excystation of ingested oocysts (19). The newly excysted sporozoites secrete adhesive molecules and other signaling proteins which have been demonstrated to play a key role in the initial attachment and cellular invasion (4, 6).The in vitro cell culture system, while limited to the asexual phase, has been a useful tool for investigating early parasite attachment and invasion and has been applied to measure Cryptosporidium infectivity and for screening of compounds for inhibitory activity (3,17). Several cell lines, including human ileocecal adenocarcinoma (HCT-8), human colonic adenocarcinoma (Caco-2), and Madin-Darby bovine kidney (MDBK) cell lines, are widely used for Cryptosporidium in vitro studies (12,22). To initiate in vitro infection, purified Cryptosporidium oocysts are often treated with sodium hypochlorite either alone or followed by sodium taurocholate (NaTC)-trypsin treatment before infecting cell monolayers. Several publications have dealt with assessment of the conditions and materials for optimal oocyst excystation and tissue culture infection by the excysted sporozoites (15,16,23,24). Upton et al. (24) investigated the optimization of infection of oocysts treated with bleach without prior excystation. Gold et al. showed that the presence of NaTC in the culture medium enhanced infection when oocysts were directly added to cell culture monolayers (11). However, the nature of this enhancement was not fully investigated, and it was assumed that the NaTC facilitated the excystation of oocysts in the culture medium (...

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“…Previous work has shown that application of bile acids can cause an increase in the levels of cytosolic [Ca 2ϩ ] in both hepatocytes (16,17) and pancreatic acinar cells (10). Specifically, bile acids activate calcium entry into the cell and cause depletion of internal calcium stores (12). Other effects not linked to calcium signaling (18) have also been observed, including an increase in the intracellular Na ϩ concentration (19) and depolarization of the inner mitochondrial membrane (20,21).…”

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confidence: 99%

“…Using this technology, we have, in addition to the well established ER Ca 2ϩ store, found a smaller intracellular Ca 2ϩ store, acidic in nature, most likely located in the secretory granules. While it is known that bile acids cause Ca 2ϩ release from the ER (12,13) and depolarization of mitochondria (20), the involvement of other organelles (32) has not been investigated. It has been shown previously that functional IP 3 Rs are needed for bile acid-induced Ca RyRs (34), controlled by cADPR or NAADP, has as yet not been studied.…”

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confidence: 99%

Bile Acids Induce Ca2+ Release from Both the Endoplasmic Reticulum and Acidic Intracellular Calcium Stores through Activation of Inositol Trisphosphate Receptors and Ryanodine Receptors

Gerasimenko

Flowerdew

Voronina

et al. 2006

Journal of Biological Chemistry

134

138

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Gallstones can cause acute pancreatitis, an often fatal disease in which the pancreas digests itself. This is probably because of biliary reflux into the pancreatic duct and subsequent bile acid action on the acinar cells. Because Ca 2؉ toxicity is important for the cellular damage in pancreatitis, we have studied the mechanisms by which the bile acid taurolithocholic acid 3-sulfate (TLC-S) liberates Ca 2؉ . Using two-photon plasma membrane permeabilization and measurement of [Ca 2؉ ] inside intracellular stores at the cell base (dominated by ER) and near the apex (dominated by secretory granules), we have characterized the Ca 2؉ release pathways. Inhibition of inositol trisphosphate receptors (IP 3 Rs), by caffeine and 2-APB, reduced Ca 2؉ release from both the ER and an acidic pool in the granular area. Inhibition of ryanodine receptors (RyRs) by ruthenium red (RR) also reduced TLC-S induced liberation from both stores. Combined inhibition of IP 3 Rs and RyRs abolished Ca 2؉ release. RyR activation depends on receptors for nicotinic acid adenine dinucleotide phosphate (NAADP), because inactivation by a high NAADP concentration inhibited release from both stores, whereas a cyclic ADPR-ribose antagonist had no effect. Bile acid-elicited intracellular Ca 2؉ liberation from both the ER and the apical acidic stores depends on both RyRs and IP 3 Rs.Bile acids, hydrophobic derivatives of cholesterol, have been suggested as a possible cause of acute pancreatitis (1). Many patients with acute pancreatitis have gallstones, blocking the ampulla of Vater, which may allow reflux of bile into the pancreatic duct system, leading to inflammation. It has been proposed that bile acids can trigger acute pancreatitis (2-4), and they have also been postulated to be tumor promoters (5), although the mechanism of action is not clear (6). Bile salts are known to induce severe experimental pancreatitis (7-9). Recent research points mainly toward abnormal calcium signaling as a possible cause of acute pancreatitis (10 -13) while casting doubt on the originally proposed ionophore-like mechanism of action of bile acids (14,15). Previous work has shown that application of bile acids can cause an increase in the levels of cytosolic [Ca 2ϩ ] in both hepatocytes (16,17) and pancreatic acinar cells (10). Specifically, bile acids activate calcium entry into the cell and cause depletion of internal calcium stores (12). Other effects not linked to calcium signaling (18) have also been observed, including an increase in the intracellular Na ϩ concentration (19) and depolarization of the inner mitochondrial membrane (20, 21).Ca 2ϩ signaling has been extensively studied in pancreatic acinar cells (22,23) and their organelles (24 -26). They are highly polarized, with distinct basal and apical poles. The secretory granules are confined to the apical region (27), which is surrounded by a perigranular Golgi apparatus and a mitochondrial belt (28, 29). All Ca 2ϩ signals start in the apical pole, and those elicited by low agonist concentrations are most...

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Deoxycholic acid activates protein kinase C and phospholipase C via increased Ca2+ entry at plasma membrane

Cited by 48 publications

References 51 publications

Critical role for calcium mobilization in activation of the NLRP3 inflammasome

Critical role for calcium mobilization in activation of the NLRP3 inflammasome

Bile Acids Enhance Invasiveness of Cryptosporidium spp. into Cultured Cells

Bile Acids Induce Ca2+ Release from Both the Endoplasmic Reticulum and Acidic Intracellular Calcium Stores through Activation of Inositol Trisphosphate Receptors and Ryanodine Receptors

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