Multiple and diverse coexpression, location, and regulation of additional SERCA2 and SERCA3 isoforms in nonfailing and failing human heart

Dally, Saoussen; Corvazier, Elisabeth; Bredoux, Raymonde; Bobe, Régis; Enouf, Jocelyne

doi:10.1016/j.yjmcc.2009.11.012

Cited by 61 publications

(66 citation statements)

References 92 publications

(122 reference statements)

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“…2A–C), consistent with a defect in diastolic function. The mitral deceleration time did not change (Table 3), and the mRNA expression of SERCA (sarco/endoplasmic reticulum calcium ATPase) and its phospholambin regulator (PLN), which are frequently, but not invariably [28, 29], diminished with diastolic dysfunction, were not altered in Acsl1 H−/− mice before or after rapamycin treatment (SERCA1/2: vehicle control, 1.11±0.24; rapamycin control, 1.41±0.35; vehicle Acsl1 H−/− , 0.83±0.09; rapamycin Acsl1 H−/− , 1.16±0.15; PLN: vehicle control, 1.11±0.0.21; rapamycin control, 1.33±0.25; vehicle Acsl1 H−/− , 0.85±0.09; rapamycin Acsl1 H−/− , 1.23±0.14; n=5–6). Because the 10 week rapamycin treatment itself induced diastolic dysfunction in both control and Acsl1 deficient mice, as previously described [30–32], it was not possible to interpret the effects of Acsl1-related mTOR activity on diastolic function.…”

Section: Resultsmentioning

confidence: 99%

Deficiency of cardiac Acyl-CoA synthetase-1 induces diastolic dysfunction, but pathologic hypertrophy is reversed by rapamycin

Paul

Grevengoed

Pascual

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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In mice with temporally-induced cardiac-specific deficiency of acyl-CoA synthetase-1 (Acsl1H−/−), the heart is unable to oxidize long-chain fatty acids and relies primarily on glucose for energy. These metabolic changes result in the development of both a spontaneous cardiac hypertrophy and increased phosphorylated S6 kinase (S6K), a substrate of the mechanistic target of rapamycin, mTOR. Doppler echocardiography revealed evidence of significant diastolic dysfunction, indicated by a reduced E/A ratio and increased mean performance index, although the deceleration time and the expression of sarco/endoplasmic reticulum calcium ATPase and phospholambin showed no difference between genotypes. To determine the role of mTOR in the development of cardiac hypertrophy, we treated Acsl1H−/− mice with rapamycin. Six to eight week old Acsl1H−/− mice and their littermate controls were given i.p. tamoxifen to eliminate cardiac Acsl1, then concomitantly treated for 10 weeks with i.p. rapamycin or vehicle alone. Rapamycin completely blocked the enhanced ventricular S6K phosphorylation and cardiac hypertrophy and attenuated the expression of hypertrophy-associated fetal genes, including α-skeletal actin and B-type natriuretic peptide. mTOR activation of the related Acsl3 gene, usually associated with pathologic hypertrophy, was also attenuated in the Acsl1H−/− hearts, indicating that alternative pathways of fatty acid activation did not compensate for the loss of Acsl1. Compared to controls, Acsl1H−/− hearts exhibited an 8-fold higher uptake of 2-deoxy[1-14C]glucose and a 35% lower uptake of the fatty acid analog 2-bromo[1-14C]palmitate. These data indicate that Acsl1-deficiency causes diastolic dysfunction and that mTOR activation is linked to the development of cardiac hypertrophy in Acsl1H−/− mice.

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Section: Resultsmentioning

confidence: 99%

Deficiency of cardiac Acyl-CoA synthetase-1 induces diastolic dysfunction, but pathologic hypertrophy is reversed by rapamycin

Paul

Grevengoed

Pascual

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…It acts as a Ca 2þ -ATPase that transfers Ca 2þ from the cytosol to the lumen of the sarcoplasmic reticulum at the expense of ATP hydrolysis during muscle relaxation (28). As one of the family members, SERCA2 is known as an important regulator of normal calcium homeostasis and signaling (29,30). Alterations in calcium-dependent signaling are involved in cell proliferation and differentiation, apoptosis, and disruption of calcium homeostasis, which may contribute to cancer development.…”

Section: Discussionmentioning

confidence: 99%

Targeting Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase 2 by Curcumin Induces ER Stress-Associated Apoptosis for Treating Human Liposarcoma

Wang

Song

et al. 2011

Molecular Cancer Therapeutics

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Human liposarcoma is the most common soft tissue sarcoma. There is no effective therapy so far except for surgery. In this study, we report for the first time that curcumin induces endoplasmic reticulum (ER) stress in human liposarcoma cells via interacting with sarcoplasmic/endoplasmic reticulum Ca 2þ -ATPase 2 (SERCA2). Curcumin dose-dependently inhibited the cell survival of human liposarcoma cell line SW872 cells, but did not affect that of human normal adipose-derived cells. Curcumin-mediated ER stress via inhibiting the activity of SERCA2 caused increasing expressions of CHOP and its transcription target death receptor 5 (TRAIL-R2), leading to a caspase-3 and caspase-8 cascade-dependent apoptosis in SW872 cells in vitro and in vivo. Moreover, 70% of human liposarcoma tissues showed an elevated SERCA2 expression compared with normal adipose tissues. Curcumin dose-dependently inhibited the activity of SERCA2, and the interaction of molecular docking and colocalization in ER of curcumin with SERCA2 were further observed. These findings suggest that curcumin may serve as a potent agent for curing human liposarcoma via targeting SERCA2. Mol Cancer Ther; 10(3); 461-71. Ó2011 AACR.

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“…The third member of the SERCA family, SERCA3 bears approximately 80% homology with other SERCA isoforms [37,41]. The ATP2A3 gene can give rise to six known SERCA3 isoforms that arise by alternative splicing in the 3’ region of the transcripts [39,42,43]. Comparative analysis of the localization and of the biochemical characteristics of various SERCA isoforms revealed significant differences.…”

Section: The Serca Multigene Family Co-expression Of Serca2 and Smentioning

confidence: 99%

Endoplasmic Reticulum Calcium Pumps and Cancer Cell Differentiation

et al. 2012

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The endoplasmic reticulum (ER) is a major intracellular calcium storage pool and a multifunctional organelle that accomplishes several calcium-dependent functions involved in many homeostatic and signaling mechanisms. Calcium is accumulated in the ER by Sarco/Endoplasmic Reticulum Calcium ATPase (SERCA)-type calcium pumps. SERCA activity can determine ER calcium content available for intra-ER functions and for calcium release into the cytosol, and can shape the spatiotemporal characteristics of calcium signals. SERCA function therefore constitutes an important nodal point in the regulation of cellular calcium homeostasis and signaling, and can exert important effects on cell growth, differentiation and survival. In several cell types such as cells of hematopoietic origin, mammary, gastric and colonic epithelium, SERCA2 and SERCA3-type calcium pumps are simultaneously expressed, and SERCA3 expression levels undergo significant changes during cell differentiation, activation or immortalization. In addition, SERCA3 expression is decreased or lost in several tumor types when compared to the corresponding normal tissue. These observations indicate that ER calcium homeostasis is remodeled during cell differentiation, and may present defects due to decreased SERCA3 expression in tumors. Modulation of the state of differentiation of the ER reflected by SERCA3 expression constitutes an interesting new aspect of cell differentiation and tumor biology.

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Multiple and diverse coexpression, location, and regulation of additional SERCA2 and SERCA3 isoforms in nonfailing and failing human heart

Cited by 61 publications

References 92 publications

Deficiency of cardiac Acyl-CoA synthetase-1 induces diastolic dysfunction, but pathologic hypertrophy is reversed by rapamycin

Deficiency of cardiac Acyl-CoA synthetase-1 induces diastolic dysfunction, but pathologic hypertrophy is reversed by rapamycin

Targeting Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase 2 by Curcumin Induces ER Stress-Associated Apoptosis for Treating Human Liposarcoma

Endoplasmic Reticulum Calcium Pumps and Cancer Cell Differentiation

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