Expression of inositol 1,4,5-trisphosphate receptor isoforms in rat cirrhosis

Dufour, Jean‐François; Lüthi, Michael; Forestier, Marc; Magnino, Fabrice

doi:10.1002/hep.510300421

Cited by 36 publications

(32 citation statements)

References 37 publications

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“…Real Time Polymerase Chain Reaction-Real time PCR analysis was performed using an Applied Biosystems 7700 sequence detector (Foster City, CA) as described (22). Sets of primers were chosen for each InsP 3 R isoform and for glyceraldehyde-3-phosphate dehydrogenase to give PCR products less than 100 base pairs in length.…”

Section: Cytosolic Camentioning

confidence: 99%

The Type III Inositol 1,4,5-Trisphosphate Receptor Preferentially Transmits Apoptotic Ca2+ Signals into Mitochondria

Mendes

Gomes

Thompson

et al. 2005

Journal of Biological Chemistry

252

217

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There are three isoforms of the inositol 1,4,5-trisphosphate receptor (InsP 3 R), each of which has a distinct effect on Ca 2؉ signaling. However, it is not known whether each isoform similarly plays a distinct role in the activation of Ca 2؉ -mediated events. To investigate this question, we examined the effects of each InsP 3 R isoform on transmission of Ca 2؉ signals to mitochondria and induction of apoptosis. Each isoform was selectively silenced using isoform-specific small interfering RNA in Chinese hamster ovary cells, which express all three InsP 3 R isoforms. ATP-induced cytosolic Ca 2؉ signaling patterns were altered, regardless of which isoform was silenced, but in a different fashion depending on the isoform. ATP also induced Ca 2؉ signals in mitochondria, which were inhibited more effectively by silencing the type III InsP 3 R than by silencing either the type I or type II isoform. The type III isoform also co-localized most strongly with mitochondria. When apoptosis was induced by activation of either the extrinsic or intrinsic apoptotic pathway, induction was reduced most effectively by silencing the type III InsP 3 R. These findings provide evidence that the type III isoform of the InsP 3 R plays a special role in induction of apoptosis by preferentially transmitting Ca 2؉ signals into mitochondria.Cytosolic Ca 2ϩ (Ca i 2ϩ ) 3 is a versatile second messenger that can simultaneously regulate multiple processes within an individual cell (1). This complex regulatory action of Ca 2ϩ is thought to result in part from the varied spatial and temporal patterns of Ca 2ϩ signals that can occur (1). These signaling patterns in turn are thought to result from special properties of the inositol-1,4,5-trisphosphate (InsP 3 ) receptor (InsP 3 R), which is the principal intracellular Ca 2ϩ release channel in most types of cells (2). The InsP 3 R is gated by InsP 3 and is localized to the endoplasmic reticulum (3) and to a lesser extent the nucleus (4, 5). There are three isoforms of the InsP 3 R, each of which has a different affinity for InsP 3 (6) and distinct functional properties at the single channel level (7,8). Each InsP 3 R isoform also has distinct effects on Ca 2ϩ signaling patterns in intact cells (9, 10). Although some cells and tissues express a single or predominant isoform of the receptor, most cells instead express two or all three InsP 3 R isoforms (9, 11-13). The presence of multiple isoforms within an individual cell suggests that Ca 2ϩ released from each isoform might mediate distinct cellular events. Apoptosis is one Ca 2ϩ -mediated event that may be influenced differently by each InsP 3 R isoform. Morphologically, apoptosis is characterized by membrane blebbing, chromatin condensation, DNA fragmentation, and eventually the formation of apoptotic bodies, which are phagocytosed by neighboring cells (14). Studies at the molecular level suggest that the InsP 3 R plays an important role in the development of apoptosis (15-17). Initial evidence suggested that Ca 2ϩ -dependent apoptotic death was ...

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Section: Cytosolic Camentioning

confidence: 99%

The Type III Inositol 1,4,5-Trisphosphate Receptor Preferentially Transmits Apoptotic Ca2+ Signals into Mitochondria

Mendes

Gomes

Thompson

et al. 2005

Journal of Biological Chemistry

252

217

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“…1a). SkHep1 cells were found to express the type II InsP3R, which is the most prevalent isoform in liver (16,29). The subcellular distribution of the InsP 3 receptor was investigated by confocal immunofluorescence.…”

Section: Characterization Of Camentioning

confidence: 99%

Molecular Basis for Pacemaker Cells in Epithelia

Leite

Hirata

Pusl

et al. 2002

Journal of Biological Chemistry

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Intercellular signaling is highly coordinated in excitable tissues such as heart, but the organization of intercellular signaling in epithelia is less clear. We examined Ca 2؉ signaling in hepatoma cells expressing the hepatocyte gap junction protein connexin32 (cx32) or the cardiac gap junction protein cx43, plus a fluorescently tagged V 1a vasopressin receptor (V 1a R Cells within excitable tissues such as the heart must act in a coordinated fashion to carry out organ-level functions such as muscle contraction to maintain blood flow. Excitation-contraction coupling in the heart is coordinated by anatomically defined pacemaker cells, and is mediated by cytosolic Ca 2ϩ signaling in individual myocytes. Intercellular Ca 2ϩ waves can be observed in the intact heart (1), and these Ca 2ϩ signaling patterns spread from cell to cell via gap junctions (2) and may relate to normal and abnormal cardiac function (1). In individual myocytes, intracellular Ca 2ϩ release occurs principally via the ryanodine receptor (RyR) 1 (3). Although RyR are spread throughout myocytes, focal clusters generate Ca 2ϩ sparks that can initiate cell-wide Ca 2ϩ signals (4 -6). Intra-and intercellular Ca 2ϩ signaling follows a different paradigm in non-excitable cells (3). Ca 2ϩ signaling in epithelial organs and in many other tissues instead occurs principally via inositol 1,4,5-trisphosphate (InsP 3 ) and the InsP 3 receptor (InsP 3 R) (3). As in the heart, cell-to-cell spread of Ca 2ϩ waves has been observed in epithelial organs, including the liver (7-9) and salivary gland (10). Intercellular Ca 2ϩ signaling follows a complex pattern in the liver, much as it does in the heart. For example, vasopressin induces Ca 2ϩ waves that spread from pericentral to periportal hepatocytes, opposite to the direction of blood flow (7, 9), and this may help direct canalicular motility and bile flow (11). Altered intercellular Ca 2ϩ signaling may contribute to the pathophysiology of certain disease states, since agents that block gap junction conductance also alter tissue function (12)(13)(14), and because certain cholestatic liver diseases are characterized by decreased expression of gap junctions and impaired transmission of intercellular Ca 2ϩ signals (15). Here we examined the conditions necessary to organize intercellular Ca 2ϩ signals in a cell system in which Ca 2ϩ signaling is mediated entirely via InsP 3 and the InsP 3 R. 8 ]vasopressin, tetracycline, penicillin, and streptomycin were obtained from Sigma; fluo-3/AM, fluo-4/AM, fura-2/AM, rhodamine-conjugated phalloidin, and caged compounds (NPE-caged InsP 3 and DM-nitrophen-EDTA) were obtained from Molecular Probes (Eugene, OR). Dulbecco's modified Eagle's medium, Liebovitz 15 (L-15) medium, and other tissue culture reagents were from Invitrogen (Basel, Switzerland). All other chemicals were of the highest quality commercially available. EXPERIMENTAL PROCEDURES Materials-[ArgAntibodies-InsP 3 receptors were labeled using an antibody from affinity-purified specific rabbit polyclonal antiserum directe...

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“…Subcellular fractionation experiments with these cells have shown that the receptor does not always co-purify with ER markers but rather with markers of the plasma membrane (Lièvremont et al, 1994;Sharp et al, 1992). Immunocytochemical experiments have indicated that the InsP3R is mainly concentrated at the lateral pole of polarized MDCK cells (Bush et al, 1994;Zhang et al, 2003) and near the apical pole of other polarized cells such as hepatocytes, (Dufour et al, 1999;Nathanson et al, 1994a), cholangiocytes (Hirata et al, 2002), pancreatic acinar cells and parotid cells (Lee et al, 1997;Nathanson et al, 1994b;Yule et al, 1997). In pancreatic acinar cells, the three receptor sub-types displayed the same sub-apical localization, indicating that this pattern of localization does not depend on the receptor subtype.…”

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confidence: 99%

The type 3 inositol 1,4,5-trisphosphate receptor is concentrated at the tight junction level in polarized MDCK cells

Colosetti

Tunwell

Cruttwell

et al. 2003

Journal of Cell Science

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The subcellular localization of inositol 1,4,5-trisphosphate(InsP3)-induced Ca2+ signals is important for the activation of many physiological functions. In epithelial cells the spatial distribution of InsP3 receptor is restricted to specific areas, but little is known about the relationship between the receptor's distribution and cell polarity. To investigate this relationship, the best known polarized cell model, MDCK, was examined. This cell line is characterized by a strong expression of the type 3 InsP3 receptor and the subcellular localization of this receptor was followed during cell polarization using immunofluorescence and confocal analysis. In non-polarized cells, including ras transformed f3 MDCK cells, the type 3 InsP3 receptor was found to co-localize with markers of the endoplasmic reticulum in the cytoplasm. In contrast, in polarized cells, this receptor was mostly distributed at the apex of the lateral plasma membrane with the markers of tight junctions, ZO-1 and occludin. The localization of the type 3 InsP3 receptor in the vicinity of tight junctions was confirmed by immunogold electron microscopy. The culture of MDCK cells in calcium-deprived medium, led to disruption of cell polarity and receptor redistribution in the cytoplasm. Addition of calcium to these deprived cells induced the restoration of polarity and the relocalization of the receptor to the plasma membrane. MDCK cells were stably transfected with a plasmid coding the full-length mouse type 1 InsP3 receptor tagged with EGFP at the C-terminus. The EGFP-tagged type 1 receptor and the endogenous type 3 co-localized in the cytoplasm of non-polarized cells and at the tight junction level of polarized cells. Thus,the localization of InsP3 receptor in MDCK depends on polarity.

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Expression of inositol 1,4,5-trisphosphate receptor isoforms in rat cirrhosis

Cited by 36 publications

References 37 publications

The Type III Inositol 1,4,5-Trisphosphate Receptor Preferentially Transmits Apoptotic Ca2+ Signals into Mitochondria

The Type III Inositol 1,4,5-Trisphosphate Receptor Preferentially Transmits Apoptotic Ca2+ Signals into Mitochondria

Molecular Basis for Pacemaker Cells in Epithelia

The type 3 inositol 1,4,5-trisphosphate receptor is concentrated at the tight junction level in polarized MDCK cells

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