Thapsigargin, a novel molecular probe for studying intracellular calcium release and storage

Thastrup, Ole; Dawson, Alan P.; Scharff, Ole; Foder, Birthe; Cullen, Peter J.; Drøbak, Bjørn K.; Bjerrum, Poul Jannik; Christensen, Søren Brøgger; Hanley, Michael R.

doi:10.1007/bf01986687

Cited by 201 publications

(195 citation statements)

References 25 publications

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“…To confirm that Ca 2ϩ participates in CAM induction signaling, leaves detached from well-watered plants were treated for 9 h with thapsigargin, an inhibitor of endomembrane Ca 2ϩ -ATPases and a releaser of intracellular Ca 2ϩ (Takemura et al, 1989;Thastrup et al, 1989). In water control leaves, a low concentration of thapsigargin (0.1 m) was sufficient to induce Ppc1 transcript accumulation in the absence of stress, whereas lower (0.01 m) and higher concentrations (3 m) were ineffective (Fig.…”

Section: Resultsmentioning

confidence: 99%

Signaling Events Leading to Crassulacean Acid Metabolism Induction in the Common Ice Plant

Taybi

Cushman

1999

Plant Physiology

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A rapid, semiquantitative reverse transcriptase-polymerase chain reaction assay was developed to investigate signal transduction events involved in the induction of Crassulacean acid metabolism (CAM) in detached common ice plant (Mesembryanthemum crystallinum) leaves. Transcript abundance of Ppc1, a gene encoding the CAM-specific isoform of phosphoenolpyruvate carboxylase, increased rapidly in response to osmotic stress (dehydration and mannitol), ionic stress (NaCl), and exogenous abscisic acid treatment, but failed to accumulate in response to exogenous cytokinin or methyl jasmonate. Stress-induced accumulation of Ppc1, GapC1, and

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Section: Resultsmentioning

confidence: 99%

Signaling Events Leading to Crassulacean Acid Metabolism Induction in the Common Ice Plant

Taybi

Cushman

1999

Plant Physiology

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“…For the elucidation of Bj-PRO-10c-mediated signal transduction, cells were exposed for 24 h to 1 mM Bj-PRO-10c in the absence or presence of 100 ng ml À1 pertussis toxin (an inhibitor of G i/o -protein-coupled metabotropic receptor activation), 10 mM ethylene glycol tetraacetic acid (EGTA; to chelate extracellular calcium), or 200 ng ml À1 thapsigargin (an inhibitor of endoplasmic reticulum Ca 2+ -ATPase). 25 Bj-PRO-10c-evoked NOx production was reduced by thapsigargin and EGTA to 0.39±0.01 and 0.59±0.09 mM, respectively. As a result of these studies, both calcium influx and the mobilization of intracellular calcium stores contributed to Bj-PRO-10c-induced signaling and NO production.…”

Section: Bj-pro-10c-induced No Production In the Brains Of Shrsmentioning

confidence: 86%

Brain nitric oxide production by a proline-rich decapeptide from Bothrops jararaca venom improves baroreflex sensitivity of spontaneously hypertensive rats

Lameu

Pontieri

Guerreiro³

et al. 2010

Hypertens Res

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Baroreflex sensitivity is disturbed in many people with cardiovascular diseases such as hypertension. Brain deficiency of nitric oxide (NO), which is synthesized by NO synthase (NOS) in the citrulline-NO cycle (with argininosuccinate synthase (ASS) activity being the rate-limiting step), contributes to impaired baroreflex. We recently showed that a decapeptide isolated from Bothrops jararaca snake venom, denoted Bj-PRO-10c, exerts powerful and sustained antihypertensive activity. Bj-PRO-10c promoted vasodilatation dependent on the positive modulation of ASS activity and NO production in the endothelium, and also acted on the central nervous system, inducing the release of GABA and glutamate, two important neurotransmitters in the regulation of autonomic systems. We evaluated baroreflex function using the regression line obtained by the best-fit points of measured heart rate (HR) and mean arterial pressure (MAP) data from spontaneously hypertensive rats (SHRs) treated with Bj-PRO-10c. We also investigated molecular mechanisms involved in this effect, both in vitro and in vivo. Bj-PRO-10c mediated an increase in baroreflex sensitivity and a decrease in MAP and HR. The effects exerted by the peptide include an increase in the gene expression of endothelial NOS and ASS. Bj-PRO-10c-induced NO production depended on intracellular calcium fluxes and the activation of a G i/o -protein-coupled metabotropic receptor. Bj-PRO-10c induced NO production and the gene expression of ASS and endothelial NOS in the brains of SHRs, thereby improving baroreflex sensitivity. Bj-PRO-10c may reveal novel approaches for treating diseases with impaired baroreflex function. Hypertension Research (2010Research ( ) 33, 1283Research ( -1288 doi:10.1038/hr.2010 Keywords: argininosuccinate synthase; baroreflex sensitivity; Bothrops jararaca venom; nitric oxide; proline-rich oligopeptide INTRODUCTIONThe gaseous messenger NO is involved mainly in the regulation of local and systemic vascular resistance, sodium balance and, consequently, blood pressure control, 1 but it is also a signaling molecule and modulator of brain function. 2 Recent studies relate NO with central cardiovascular control through the regulation of the cardiac and vascular autonomic system via the modulation of the central sites of cardiovascular autonomic neural integration. 3,4 NO is generated in the citrulline-NO cycle by NO synthase (NOS) using L-arginine as a substrate. Three isoforms of NOS have been described: calcium-dependent endothelial (eNOS) and neuronal (nNOS) isoforms and inducible NOS. The expression and activity

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“…The kidneys ( n ϭ 6) were then treated with thapsigargin (1 M), an inhibitor of endoplasmic reticulum Ca-ATPase (19). After a 30-min reequilibration period, AngII (0.1-0.3 nM) was added in a cumulative manner.…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, the influence of N -ethylmaleimide, a GTP-binding (G) protein antagonist that inhibits the Gi protein family (18), or of thapsigargin, an endoplasmic reticulum calcium pump inhibitor (19), on renal microvascular constriction by AngII was examined. Our results suggest that in afferent arterioles, AngII elicits intracellular calcium mobilization, possibly through Gq proteins, that is required to recruit voltage-dependent calcium channels.…”

Section: Introductionmentioning

confidence: 99%

Cellular mechanisms mediating rat renal microvascular constriction by angiotensin II.

Takenaka¹,

Suzuki²,

Fujiwara³

et al. 1997

J. Clin. Invest.

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To assess cellular mechanisms mediating afferent (AA) and efferent arteriolar (EA) constriction by angiotensin II (AngII), experiments were performed using isolated perfused hydronephrotic kidneys. In the first series of studies, AngII (0.3 nM) constricted AAs and EAs by 29 Ϯ 3 ( n ϭ 8, P Ͻ 0.01) and 27 Ϯ 3% ( n ϭ 8, P Ͻ 0.01), respectively. Subsequent addition of nifedipine restored AA but not EA diameter. Manganese (8 mM) reversed EA constriction by 65 Ϯ 9% ( P Ͻ 0.01). In the second group, the addition of N -ethylmaleimide (10 M), a Gi/Go protein antagonist, abolished AngIIinduced EA ( n ϭ 6) but not AA constriction ( n ϭ 6). In the third series of experiments, treatment with 2-nitro-4-carboxyphenyl-N , N -diphenyl-carbamate (200 M), a phospholipase C inhibitor, blocked both AA and EA constriction by AngII ( n ϭ 6 for each). In the fourth group, thapsigargin (1 M) prevented AngII-induced AA constriction ( n ϭ 8) and attenuated EA constriction (8 Ϯ 2% decrease in EA diameter at 0.3 nM AngII, n ϭ 8, P Ͻ 0.05). Subsequent addition of manganese (8 mM) reversed EA constriction. Our data provide evidence that in AAs, AngII stimulates phospholipase C with subsequent calcium mobilization that is required to activate voltage-dependent calcium channels. Our results suggest that AngII constricts EAs by activating phospholipase C via the Gi protein family, thereby eliciting both calcium mobilization and calcium entry. ( J.

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Thapsigargin, a novel molecular probe for studying intracellular calcium release and storage

Cited by 201 publications

References 25 publications

Signaling Events Leading to Crassulacean Acid Metabolism Induction in the Common Ice Plant

Signaling Events Leading to Crassulacean Acid Metabolism Induction in the Common Ice Plant

Brain nitric oxide production by a proline-rich decapeptide from Bothrops jararaca venom improves baroreflex sensitivity of spontaneously hypertensive rats

Cellular mechanisms mediating rat renal microvascular constriction by angiotensin II.

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