Abnormal intracellular Ca2+homeostasis and disease

Missiaen, Ludwig; Robberecht, Wim; Bosch, Ludo Van Den; Callewaert, Geert; Parys, Jan B.; Wuytack, Frank; Raeymaekers, Luc; Nilius, Bernd; Eggermont, Jan; Smedt, Humbert De

doi:10.1054/ceca.2000.0131

Cited by 204 publications

(139 citation statements)

References 243 publications

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“…The Ca 2ϩ content in the SR has a vital role in shaping the normal pattern of Ca 2ϩ release during Ca 2ϩ signaling. Abnormal SR Ca 2ϩ content has been shown to have devastating cellular consequences and implications in many cell systems (38,39). In Pkd2 ϩ/Ϫ aortic vascular smooth muscle cells, the decreased amount of Ca 2ϩ in the SR resulted in an increase in cellular proliferation and apoptosis and was hypothesized to be the basis for the cardiovascular abnormalities encountered in patients with ADPKD (34).…”

Section: Discussionmentioning

confidence: 99%

Regulation of ryanodine receptor-dependent calcium signaling by polycystin-2

Anyatonwu¹,

Estrada²,

Tian³

et al. 2007

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

143

139

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Mutations in polycystin-2 (PC2) cause autosomal dominant polycystic kidney disease. A function for PC2 in the heart has not been described. Here, we show that PC2 coimmunoprecipitates with the cardiac ryanodine receptor (RyR2) from mouse heart. Biochemical assays showed that the N terminus of PC2 binds the RyR2, whereas the C terminus only binds to RyR2 in its open state. Lipid bilayer electrophysiological experiments indicated that the C terminus of PC2 functionally inhibited RyR2 channel activity in the presence of calcium (Ca 2؉ ). Pkd2 ؊/؊ cardiomyocytes had a higher frequency of spontaneous Ca 2؉ oscillations, reduced Ca 2؉ release from the sarcoplasmic reticulum stores, and reduced Ca 2؉ content compared with Pkd2 ؉/؉ cardiomyocytes. In the presence of caffeine, Pkd2 ؊/؊ cardiomyocytes exhibited decreased peak fluorescence, a slower rate of rise, and a longer duration of Ca 2؉ transients compared with Pkd2 ؉/؉ . These data suggest that PC2 is important for regulation of RyR2 function and that loss of this regulation of RyR2, as occurs when PC2 is mutated, results in altered Ca 2؉ signaling in the heart. intracellular calcium channel ͉ polycystic kidney disease ͉ lipid bilayer ͉ calcium imaging ͉ cardiac cells

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Section: Discussionmentioning

confidence: 99%

Regulation of ryanodine receptor-dependent calcium signaling by polycystin-2

Anyatonwu¹,

Estrada²,

Tian³

et al. 2007

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

143

139

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“…Ca 2+ acts as a second messenger in a number of different signaling pathways and plays a critical role in a myriad of different physiological and pathological processes, including oncogenesis (Richter, 1993;Missiaen et al, 2000). In almost all known cases Ca 2+ signaling is initiated by extracellular events or stimuli (Riccardi, 1999;Hofer et al, 2000) in communication with cell's plasma membrane.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial stress-induced calcium signaling, phenotypic changes and invasive behavior in human lung carcinoma A549 cells

Amuthan

Biswas

Ananadatheerthavarada

et al. 2002

Oncogene

227

265

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We have investigated mechanisms of mitochondrial stressinduced phenotypic changes and cell invasion in tumorigenic but poorly invasive human pulmonary carcinoma A549 cells that were partly depleted of mitochondrial DNA (mtDNA). Depletion of mtDNA (genetic stress) caused a markedly lower electron transport-coupled ATP synthesis, loss of mitochondrial membrane potential, elevation of steady state [Ca 2+ ] c , and notably induction of both glycolysis and gluconeogenic pathway enzymes. Markers of tumor invasion, cathepsin L and TGFb1, were overexpressed; calcium-dependent MAP kinases (ERK1 and ERK2) and calcineurin were activated. The levels of anti-apoptotic proteins Bcl2 and Bcl-X L were increased, and the cellular levels of pro-apoptotic proteins Bid and Bax were reduced. Both mtDNA-depleted cells (genetic stress) and control cells treated with carbonyl cyanide m-chlorophenylhydrazone (metabolic stress) exhibited higher invasive behavior than control cells in a Matrigel basement membrane matrix assay system. MtDNA-depleted cells stably expressing anti-sense cathepsin L RNA, TGFb1 RNA, or treated with specific inhibitors showed reduced invasion. Reverted cells with 80% of control cell mtDNA exhibited marker protein levels, cell morphology and invasive property closer to control cells. Our results suggest that the mitochondriato-nucleus signaling pathway operating through increased [Ca 2+ ] c plays an important role in cancer progression and metastasis. Oncogene (2002Oncogene ( ) 21, 7839 -7849. doi:10.1038 Keywords: mitochondria; calcium signaling; cathepsin L; TGFb; tumor invasion; MAP kinases IntroductionThe role of mitochondria in carcinogenesis was initially suggested by Warburg et al. (1926;Warburg, 1956), based on the observation that number of experimentally induced rodent tumors exhibit reduced respiration-coupled oxidative metabolism and increased glycolysis. Since then, altered mitochondrial morphology, as well as changes in mitochondrial enzyme patterns and membrane transport systems, have been described in several tumor types (Zafar et al., 1982). Cell fusion studies (Jonasson et al., 1977;Howell and Sager, 1978;Giguere and Morais, 1981) also suggest that unknown cytoplasmic elements may play roles in carcinogenesis. Fusion between normal cytoplasm and karyoplasts from malignant phenotypes resulted in the ablation of tumorigenicity (Israel and Schaeffer, 1987) and conversely, the cytoplasm of the malignant phenotype could transfer the malignancy to the karyoplasts from normal cells (Israel and Schaeffer, 1988). Studies using mitochondrial DNA (mtDNA)-depleted tumor cells to evaluate the role of mtDNA, and thus mitochondrial function in tumorigenicity have yielded mixed results (Giguere and Morais, 1981;Morais et al., 1994;Cavalli et al., 1997;Cavalli and Liang, 1998;Hofhaus and Gattermann, 1999). Cavalli et al. (1997) found diminished tumor formation by glioblastoma cells following depletion of mtDNA (r 0 cells) with ethidium bromide treatment, while Morais et al. (1994) found increased capacity to p...

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“…ryanodine may be due to a decrease in [Ca 2C ] i at supraspinal level. Abnormalities of RyRs have been related to the induction of several skeletalemuscle pathologies such as malignant hyperthermia, porcine stress syndrome, centralcore disease (Missiaen et al, 2000). The etiopathological role of RyRs has also been postulated at the central nervous system level.…”

Section: Discussionmentioning

confidence: 99%

Blockade of intracellular calcium release induces an antidepressant-like effect in the mouse forced swimming test

2006

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The role of intracellular calcium in the modulation of a depressant-like condition was investigated in the mouse forced swimming test. I.c.v. administration of TMB-8 (0.23e46.3 nmol per mouse), a blocker of Ca 2C release from intracellular stores, decreased the mouse immobility time. I.c.v. injection of thapsigargin (0.003e3 nmol per mouse), compound which selectively inhibits Ca 2C uptake into the endoplasmic reticulum, produced, 60 min after administration, a depressant-like condition. Xestospongin C (1e100 pmol per mouse i.c.v.), an InsP 3 -receptor antagonist, decreased the mouse immobility time. By contrast, D-myo-inositol (5.4e540 pmol per mouse i.c.v.), compound which produces InsP 3 , resulted in a depressant-like effect. Similarly, ryanodine (0.1e600 pmol per mouse i.c.v.), an RyR antagonist, decreased the immobility time values whereas the administration of 4-chloro-m-cresol (0.1e100 pmol per mouse i.c.v.), an RyR agonist, showed an opposite effect. The antidepressant-like effects observed with TMB-8, xestospongin C and ryanodine were comparable to that produced by the antidepressant drugs amitriptyline and clomipramine. The treatments employed did not produce any behavioural impairment of mice as revealed by the rota-rod and hole board tests indicating that the antidepressant-and depressant-like effects were not due to a compromised locomotor activity and spontaneous motility of the treated animals. These results indicate that a central variation in intracellular calcium contents is involved in the modulation of a depressive-like condition in the mouse forced swimming test. In particular, the blockade of both InsP 3 Rs and RyRs appears to play an important role in the induction of an antidepressant-like effect, whereas the stimulation of these receptors is involved in a depressant-like response of mice.

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Abnormal intracellular Ca2+homeostasis and disease

Cited by 204 publications

References 243 publications

Regulation of ryanodine receptor-dependent calcium signaling by polycystin-2

Regulation of ryanodine receptor-dependent calcium signaling by polycystin-2

Mitochondrial stress-induced calcium signaling, phenotypic changes and invasive behavior in human lung carcinoma A549 cells

Blockade of intracellular calcium release induces an antidepressant-like effect in the mouse forced swimming test

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