Hydrogen peroxide induces intracellular calcium oscillations in human aortic endothelial cells

Qinghua Hu, Stefano Corda, Jay L. Zweier, Maurizio C. Capogrossi, Roy C. Ziegelstein

Research output: Contribution to journalArticle

Abstract

Background - Because the vascular endothelium is exposed to oxidant stress resulting from ischemia/reperfusion and from the products of polymorphonuclear leukocytes or monocytes, studies were performed to examine the effect of hydrogen peroxide (1 μmol/L to 10 mmol/L) on endothelial Ca2+ signaling. Methods and Results - At low concentrations (1 to 10 μmol/L), hydrogen peroxide did not affect intracellular Ca2+ concentration in subconfluent, indo 1-loaded human aortic endothelial monolayers. At a concentration of 100 μmol/L hydrogen peroxide, intracellular free Ca2+ gradually increased from 125.3±6.8 to 286.3±19.9 nmol/L over 4.2±0.9 minutes before repetitive Ca2+ oscillations were observed, consisting of an initial large, transient spike of κ1 μmol/L foLLowed by several spikes of decreasing amplitudes at a frequency of 0.7 ± 0.1 min-1 over 12.0 ± 1.1 minutes. After these oscillations, intracellular Ca2+ reached a plateau of 543.4±64.0 nmol/L, which was maintained above baseline levels for >5 minutes and then partially reversible on washout of hydrogen peroxide in most monolayers. Intracellular Ca2+ oscillations were typically observed when monolayers were exposed to 100 to 500 μmol/L hydrogen peroxide. Higher concentrations of hydrogen peroxide (1 and 10 mmol/L) increased intracellular Ca2+ but only rarely (2 of 6 monolayers at 1 mmol/L) or never (at 10 mmol/L) stimulated intracellular Ca2+ oscillations. Removal of Ca2+ from the buffer either before hydrogen peroxide stimulation or during an established response did not block intracellular Ca2+ oscillations in response to 100 μmol/L hydrogen peroxide, but prior depletion of an intracellular Ca2+ store with either caffeine, histamine, or thapsigargin abolished Ca2+ oscillations. Conclusions - Hydrogen peroxide induces concentration-dependent intracellular Ca2+ oscillations in human endothelial cells, which results from release of an endoplasmic reticulum Ca2+ store. Because oxidant production appears to occur in the micromolar range in the postischemic/anoxic endothelium and is associated with impaired endothelium-dependent relaxation, the effects of micromolar concentrations of hydrogen peroxide on endothelial Ca2+ signaling described in the present study may be important in the pathogenesis of postischemic endothelial dysfunction.

Original languageEnglish
Pages (from-to)268-275
Number of pages8
JournalCirculation
Volume97
Issue number3
Publication statusPublished - Jan 27 1998

Fingerprint

Calcium Signaling
Hydrogen Peroxide
Endothelial Cells
Oxidants
Endothelium
Thapsigargin
Vascular Endothelium
Caffeine
Endoplasmic Reticulum
Histamine
Reperfusion
Monocytes
Buffers
Neutrophils
Ischemia

Keywords

  • Calcium
  • Endothelium
  • Free radicals

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Hu, Q., Corda, S., Zweier, J. L., Capogrossi, M. C., & Ziegelstein, R. C. (1998). Hydrogen peroxide induces intracellular calcium oscillations in human aortic endothelial cells. Circulation, 97(3), 268-275.

Hydrogen peroxide induces intracellular calcium oscillations in human aortic endothelial cells. / Hu, Qinghua; Corda, Stefano; Zweier, Jay L.; Capogrossi, Maurizio C.; Ziegelstein, Roy C.

In: Circulation, Vol. 97, No. 3, 27.01.1998, p. 268-275.

Research output: Contribution to journalArticle

Hu, Q, Corda, S, Zweier, JL, Capogrossi, MC & Ziegelstein, RC 1998, 'Hydrogen peroxide induces intracellular calcium oscillations in human aortic endothelial cells', Circulation, vol. 97, no. 3, pp. 268-275.
Hu Q, Corda S, Zweier JL, Capogrossi MC, Ziegelstein RC. Hydrogen peroxide induces intracellular calcium oscillations in human aortic endothelial cells. Circulation. 1998 Jan 27;97(3):268-275.
Hu, Qinghua ; Corda, Stefano ; Zweier, Jay L. ; Capogrossi, Maurizio C. ; Ziegelstein, Roy C. / Hydrogen peroxide induces intracellular calcium oscillations in human aortic endothelial cells. In: Circulation. 1998 ; Vol. 97, No. 3. pp. 268-275.
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T1 - Hydrogen peroxide induces intracellular calcium oscillations in human aortic endothelial cells

AU - Hu, Qinghua

AU - Corda, Stefano

AU - Zweier, Jay L.

AU - Capogrossi, Maurizio C.

AU - Ziegelstein, Roy C.

PY - 1998/1/27

Y1 - 1998/1/27

N2 - Background - Because the vascular endothelium is exposed to oxidant stress resulting from ischemia/reperfusion and from the products of polymorphonuclear leukocytes or monocytes, studies were performed to examine the effect of hydrogen peroxide (1 μmol/L to 10 mmol/L) on endothelial Ca2+ signaling. Methods and Results - At low concentrations (1 to 10 μmol/L), hydrogen peroxide did not affect intracellular Ca2+ concentration in subconfluent, indo 1-loaded human aortic endothelial monolayers. At a concentration of 100 μmol/L hydrogen peroxide, intracellular free Ca2+ gradually increased from 125.3±6.8 to 286.3±19.9 nmol/L over 4.2±0.9 minutes before repetitive Ca2+ oscillations were observed, consisting of an initial large, transient spike of κ1 μmol/L foLLowed by several spikes of decreasing amplitudes at a frequency of 0.7 ± 0.1 min-1 over 12.0 ± 1.1 minutes. After these oscillations, intracellular Ca2+ reached a plateau of 543.4±64.0 nmol/L, which was maintained above baseline levels for >5 minutes and then partially reversible on washout of hydrogen peroxide in most monolayers. Intracellular Ca2+ oscillations were typically observed when monolayers were exposed to 100 to 500 μmol/L hydrogen peroxide. Higher concentrations of hydrogen peroxide (1 and 10 mmol/L) increased intracellular Ca2+ but only rarely (2 of 6 monolayers at 1 mmol/L) or never (at 10 mmol/L) stimulated intracellular Ca2+ oscillations. Removal of Ca2+ from the buffer either before hydrogen peroxide stimulation or during an established response did not block intracellular Ca2+ oscillations in response to 100 μmol/L hydrogen peroxide, but prior depletion of an intracellular Ca2+ store with either caffeine, histamine, or thapsigargin abolished Ca2+ oscillations. Conclusions - Hydrogen peroxide induces concentration-dependent intracellular Ca2+ oscillations in human endothelial cells, which results from release of an endoplasmic reticulum Ca2+ store. Because oxidant production appears to occur in the micromolar range in the postischemic/anoxic endothelium and is associated with impaired endothelium-dependent relaxation, the effects of micromolar concentrations of hydrogen peroxide on endothelial Ca2+ signaling described in the present study may be important in the pathogenesis of postischemic endothelial dysfunction.

AB - Background - Because the vascular endothelium is exposed to oxidant stress resulting from ischemia/reperfusion and from the products of polymorphonuclear leukocytes or monocytes, studies were performed to examine the effect of hydrogen peroxide (1 μmol/L to 10 mmol/L) on endothelial Ca2+ signaling. Methods and Results - At low concentrations (1 to 10 μmol/L), hydrogen peroxide did not affect intracellular Ca2+ concentration in subconfluent, indo 1-loaded human aortic endothelial monolayers. At a concentration of 100 μmol/L hydrogen peroxide, intracellular free Ca2+ gradually increased from 125.3±6.8 to 286.3±19.9 nmol/L over 4.2±0.9 minutes before repetitive Ca2+ oscillations were observed, consisting of an initial large, transient spike of κ1 μmol/L foLLowed by several spikes of decreasing amplitudes at a frequency of 0.7 ± 0.1 min-1 over 12.0 ± 1.1 minutes. After these oscillations, intracellular Ca2+ reached a plateau of 543.4±64.0 nmol/L, which was maintained above baseline levels for >5 minutes and then partially reversible on washout of hydrogen peroxide in most monolayers. Intracellular Ca2+ oscillations were typically observed when monolayers were exposed to 100 to 500 μmol/L hydrogen peroxide. Higher concentrations of hydrogen peroxide (1 and 10 mmol/L) increased intracellular Ca2+ but only rarely (2 of 6 monolayers at 1 mmol/L) or never (at 10 mmol/L) stimulated intracellular Ca2+ oscillations. Removal of Ca2+ from the buffer either before hydrogen peroxide stimulation or during an established response did not block intracellular Ca2+ oscillations in response to 100 μmol/L hydrogen peroxide, but prior depletion of an intracellular Ca2+ store with either caffeine, histamine, or thapsigargin abolished Ca2+ oscillations. Conclusions - Hydrogen peroxide induces concentration-dependent intracellular Ca2+ oscillations in human endothelial cells, which results from release of an endoplasmic reticulum Ca2+ store. Because oxidant production appears to occur in the micromolar range in the postischemic/anoxic endothelium and is associated with impaired endothelium-dependent relaxation, the effects of micromolar concentrations of hydrogen peroxide on endothelial Ca2+ signaling described in the present study may be important in the pathogenesis of postischemic endothelial dysfunction.

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