“Tell Me Where Is Calcium Bred”: Clarifying the Roles of Nuclear Calcium

Malviya, Anant N.; Rogue, P

doi:10.1016/s0092-8674(00)80895-8

Cited by 119 publications

(96 citation statements)

References 37 publications

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“…In line with these data in beta cells, in endothelial cells the 54,193,194,195,196,197]. Thereby, the impact of Ca 2+ on gene expression exceeded its role in the nuclear envelope, where Ca 2+ is essential for modulating immediate early genes by modulating the DNA-binding of transcription factors (e. g. cAMP-responsive element binding protein CREB [191,192,198,199,200]). Ca 2+ triggers the activation of transcription factors such as the nuclear factor of activated T cells (NFAT) [201,202,203,204,205,206] and the serum response factor-related proteins (RSRF or the myocyte enhancer factor 2 (MEF2) [207]) by calcineurin [208] or Ca 2+ -sensitive kinases (e. g. Cam-kinase IV [207]).…”

Section: Nomentioning

confidence: 54%

Vascular targets of redox signalling in diabetes mellitus

2002

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There is overwhelming evidence for an involvement of reactive oxygen species (ROS) in the pathogenesis of diabetes-associated vascular complications. However, neither the exact source of the ROS initiating cascades leading to cell dysfunction in diabetes nor their chemical nature is fully understood. Furthermore, despite our knowledge of the crucial role of ROS in diabetes, little is known about the actual targets and the molecular consequences of the interaction of ROS with cellular signalling pathways.Therefore, we aim to provide an overview of ROS (i. e. O 2 · , NO · , ONOO  and H 2 O 2 ) and their vascular sources in diabetes and to summarise recent knowledge on the mechanisms underlying increased ROS production within the vascular wall. In addition, possible targets of diabetes and ROS within the vasculature are discussed. These include, the effects of ROS on small guanine nucleotide binding proteins, the cytoskeleton, protein kinases (e. g. tyrosine kinases), metalloproteinases, ion homeostasis and transcriptional regulation.Such analysis makes it clear that the generation of ROS could affect a large number of various signalling pathways and proteins. Thus, a better knowledge of the functional diversity and pathological consequences of each individual pathway activated by ROS is essential to understand the mechanisms of diabetesassociated vascular complications. [Diabetologia (2002) 45:476±494]

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Section: Nomentioning

confidence: 54%

Vascular targets of redox signalling in diabetes mellitus

2002

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“…f luorescence intensity in the nucleus and cytosol (55,57,58). Therefore, for these studies, nuclear and cytosolic Ca 2ϩ signals were normalized to the same baseline and peak value to focus on the temporal differences between the two tracings ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Nuclear and cytosolic calcium are regulated independently

Leite

Thrower

Echevarria

et al. 2003

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

191

166

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Nuclear calcium (Ca 2؉ ) regulates a number of important cellular processes, including gene transcription, growth, and apoptosis. However, it is unclear whether Ca 2؉ signaling is regulated differently in the nucleus and cytosol. To investigate this possibility, we examined subcellular mechanisms of Ca 2؉ release in the HepG2 liver cell line. The type II isoform of the inositol 1,4,5-trisphosphate (InsP 3) receptor (InsP 3R) was expressed to a similar extent in the endoplasmic reticulum and nucleus, whereas the type III InsP 3R was concentrated in the endoplasmic reticulum, and the type I isoform was not expressed. Ca 2؉ signals induced by low InsP3 concentrations started earlier or were larger in the nucleus than in the cytosol, indicating higher sensitivity of nuclear Ca 2؉ stores for InsP3. Nuclear InsP3R channels were active at lower InsP 3 concentrations than InsP3R from cytosol. Enriched expression of type II InsP 3R in the nucleus results in greater sensitivity of the nucleus to InsP 3, thus providing a mechanism for independent regulation of Ca 2؉ -dependent processes in this cellular compartment.

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“…45,46) or in the nuclear envelope (10,47,48). A nuclear Ca 2ϩ signaling cascade, including nuclear InsP 3 receptors and CaMKII␦, could play a major role in coupling Ca 2ϩ signals to transcriptional events in cardiomyocytes.…”

Section: Selective Effects Of Camkii Isoforms On Phosphorylation Of Camentioning

confidence: 99%

CaMKIIδ Isoforms Differentially Affect Calcium Handling but Similarly Regulate HDAC/MEF2 Transcriptional Responses

Zhang

Kohlhaas

Backs

et al. 2007

Journal of Biological Chemistry

188

168

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The ␦ B and ␦ C splice variants of Ca 2؉ /calmodulin-dependent protein kinase II (CaMKII), which differ by the presence of a nuclear localization sequence, are both expressed in cardiomyocytes. We used transgenic (TG) mice and CaMKII expression in cardiomyocytes to test the hypothesis that the CaMKII␦ C isoform regulates cytosolic Ca 2؉ handling and the ␦ B isoform, which localizes to the nucleus, regulates gene transcription. Phosphorylation of CaMKII sites on the ryanodine receptor (RyR) and on phospholamban (PLB) were increased in CaMKII␦ C TG. This was associated with markedly enhanced sarcoplasmic reticulum (SR) Ca 2؉ spark frequency and decreased SR Ca 2؉ content in cardiomyocytes. None of these parameters were altered in TG mice expressing the nuclear-targeted CaMKII␦ B . In contrast, cardiac expression of either CaMKII␦ B or ␦ C induced transactivation of myocyte enhancer factor 2 (MEF2) gene expression and up-regulated hypertrophic marker genes. Studies using rat ventricular cardiomyocytes confirmed that CaMKII␦ B and ␦ C both regulate MEF2-luciferase gene expression, increase histone deacetylase 4 (HDAC4) association with 14-3-3, and induce HDAC4 translocation from nucleus to cytoplasm, indicating that either isoform can stimulate HDAC4 phosphorylation. Finally, HDAC4 kinase activity was shown to be increased in cardiac homogenates from either CaMKII␦ B or ␦ C TG mice. Thus CaMKII␦ isoforms have similar effects on hypertrophic gene expression but disparate effects on Ca 2؉ handling, suggesting distinct roles for CaMKII␦ isoform activation in the pathogenesis of cardiac hypertrophy versus heart failure.is the predominant isoform of CaMKII in the heart. Splice variants differing in the presence of a nuclear localization sequence (NLS) show distinct subcellular targeting to either cytoplasmic or nuclear compartments (1-3). The CaMKII␦ B isoform contains an 11 amino acid NLS that is absent from ␦ C . Thus CaMKII heteromers comprised predominantly of ␦ B subunits localize to the nucleus while those with predominantly ␦ C localize to the cytoplasm (1-3). We recently demonstrated that both ␦ B and ␦ C CaMKII are activated in response to pressure overload induced by thoracic aortic banding but that expression of these isoforms is differentially regulated (4). The possibility that there are discrete roles for these two isoforms in regulating Ca 2ϩ homeostasis and gene transcription has not yet been explored.CaMKII has long been implicated as a regulator of Ca 2ϩ homeostasis and excitation-contraction (E-C) coupling in ventricular myocytes. This enzyme has been shown to phosphorylate proteins involved in sarcoplasmic reticulum (SR) Ca 2ϩ handling including the cardiac ryanodine receptors (RyR2) and phospholamban (PLB) (4 -10). Phosphorylation of the RyR2 appears to alter its channel open probability (9 -11) while phosphorylation of PLB by CaMKII can regulate SR Ca 2ϩ uptake (10, 12). Altered intracellular Ca 2ϩ handling plays an important role in the pathogenesis of heart failure with changes in Ca 2ϩ cycling pr...

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“Tell Me Where Is Calcium Bred”: Clarifying the Roles of Nuclear Calcium

Abstract: the use of Ca 2ϩ -sensitive fluorescent indicators. In particular it has shifted the emphasis from the long-term determination of Ca 2ϩ level to the study of short-term delays in the transmission of the cytosolic Ca 2ϩ waves to the nucleus. Cytosolic Ca 2ϩ waves depend upon the

Cited by 119 publications

References 37 publications

Vascular targets of redox signalling in diabetes mellitus

Vascular targets of redox signalling in diabetes mellitus

Nuclear and cytosolic calcium are regulated independently

CaMKIIδ Isoforms Differentially Affect Calcium Handling but Similarly Regulate HDAC/MEF2 Transcriptional Responses

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