Hydrogen peroxide mobilizes Ca2+ through two distinct mechanisms in rat hepatocytes

Sato, Hirohiko; Takeo, Teruko; Liu, Qiang; Nakano, Kyoko; Osanai, Tomohiro; Suga, Sechiko; Wakui, Makoto; Wu, Jie

doi:10.1038/aps.2008.4

Cited by 23 publications

(16 citation statements)

References 45 publications

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“…In our study, the role of PLC γ 1-IP 3 R signalling in SOC was examined, and the results showed that H 2 O 2 -induced elevated [Ca 2+ ] i was almost abolished and that the increased phosphorylation of PLC γ 1 was reduced when cells were pre-treated with the generic PLC inhibitor U73122 or the IP 3 R inhibitor 2-APB. These findings are in agreement with earlier publications reporting that the phosphorylation and activation of PLC by a sulfhydryl oxidation-dependent mechanism, which leads to increased IP 3 synthesis and subsequent activation of the IP 3 receptor, induces the release of Ca 2+ from intracellular stores 37,38 and that the H 2 O 2 -induced [Ca 2+ ] i rise could be prevented by U73122 or 2-APB. 39 SOC is defined as enhanced Ca 2+ import from the extracellular space after depletion of calcium in the ER.…”

Section: Discussionsupporting

confidence: 93%

HMGB1 release by H2O2-induced hepatocytes is regulated through calcium overload and 58-F interference

Zhao

Yan

et al. 2017

Cell Death Discov.

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HMGB1 is passively released by injured or dying cells and aggravates inflammatory processes. The release of HMGB1 and calcium overload have each been reported to be important mediators of H2O2-induced injury. However, a potential connection between these two processes remains to be elucidated. In the present study, we employed H2O2-induced hepatocytes to investigate how calcium overload takes place during cellular injury and how the extracellular release of HMGB1 is regulated by this overload. In addition, we investigated the use of 58-F, a flavanone extracted from Ophiopogon japonicus, as a potential therapeutic drug. We show that the PLCγ1–IP3R–SOC signalling pathway participates in the H2O2-induced disturbance of calcium homoeostasis and leads to calcium overload in hepatocytes. After a rise in intracellular calcium, two calcium-dependent enzymes, PKCα and CaMKIV, are activated and translocated from the cytoplasm to the nucleus to modify HMGB1 phosphorylation. In turn, this promotes HMGB1 translocation from the nucleus to the cytoplasm and subsequent extracellular release. 58-F effectively rescued the hepatocytes by suppressing the PLCγ1–IP3R–SOC signalling pathway and decreasing the calcium concentration in cells, thus reducing HMGB1 release.

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Section: Discussionsupporting

confidence: 93%

HMGB1 release by H2O2-induced hepatocytes is regulated through calcium overload and 58-F interference

Zhao

Yan

et al. 2017

Cell Death Discov.

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“…H 2 O 2 has been shown to elevate intracellular calcium concentrations through both influx and release of intracellular stores (35). To measure the requirement for intracellular calcium in the augmentation of flagellin-induced IL-8, we pretreated Caco-2 cells with the cell-permeable calcium chelator BAPTA-AM prior to the addition of H 2 O 2 .…”

Section: Resultsmentioning

confidence: 99%

Oxidative stress enhances IL-8 and inhibits CCL20 production from intestinal epithelial cells in response to bacterial flagellin

Ivison

Himmel

Sheridan

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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Intestinal epithelial cells act as innate immune sentinels, as the first cells that encounter diarrheal pathogens. They use pattern recognition molecules such as the Toll-like receptors (TLRs) to identify molecular signals found on microbes but not host cells or food components. TLRs cannot generally distinguish the molecular signals on pathogenic bacteria from those found in commensals, yet under healthy conditions epithelial immune responses are kept in check. We hypothesized that, in the setting of tissue damage or stress, intestinal epithelial cells would upregulate their responses to TLR ligands to reflect the greater need for immediate protection against pathogens. We treated Caco-2 cells with the TLR5 agonist flagellin in the presence or absence of H(2)O(2) and measured chemokine production and intracellular signaling pathways. H(2)O(2) increased flagellin-induced IL-8 (CXCL8) production in a dose-dependent manner. This was associated with synergistic phosphorylation of p38 MAP kinase and with prolonged I-kappaB degradation and NF-kappaB activation. The H(2)O(2)-mediated potentiation of IL-8 production required the activity of p38, tyrosine kinases, phospholipase Cgamma, and intracellular calcium, but not protein kinase C or protein kinase D. H(2)O(2) prolonged and augmented NF-kappaB activation by flagellin. In contrast to IL-8, CCL20 (MIP3alpha) production by flagellin was reduced by H(2)O(2), and this effect was not calcium dependent. Oxidative stress biases intestinal epithelial responses to flagellin, leading to increased production of IL-8 and decreased production of CCL20. This suggests that epithelial cells are capable of sensing the extracellular environment and adjusting their antimicrobial responses accordingly.

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“…Also, the positive shift in reversal potential may suggest that additional channels contribute. For instance, H 2 O 2 also increases conductance of non-selective cation channels (Simon et al , 2002; Sato et al , 2009) and sodium channels (Meng and Nie, 2004). The potential increase of sodium influx by H 2 O 2 through these channels is consistent with greater ease to reach THR in our current study, as demonstrated in our DE protocols.…”

Section: Discussionmentioning

confidence: 99%

H2O2 induces delayed hyperexcitability in nucleus tractus solitarii neurons

Ostrowski¹,

Hasser²,

Heesch³

et al. 2014

Neuroscience

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Hydrogen peroxide (H2O2) is a stable reactive oxygen species and potent neuromodulator of cellular and synaptic activity. Centrally, endogenous H2O2 is elevated during bouts of hypoxia-reoxygenation, a variety of disease states, and aging. The nucleus tractus solitarii (nTS) is the central termination site of visceral afferents for homeostatic reflexes and contributes to reflex alterations during these conditions. We determined the extent to which H2O2 modulates synaptic and membrane properties in nTS neurons in rat brainstem slices. Stimulation of the tractus solitarii (which contains the sensory afferent fibers) evoked synaptic currents that were not altered by 10 – 500 μM H2O2. However, 500 μM H2O2 modulated several intrinsic membrane properties of nTS neurons, including a decrease in input resistance, hyperpolarization of resting membrane potential (RMP) and action potential (AP) threshold (THR), and an initial reduction in AP discharge to depolarizing current. H2O2 increased conductance of barium-sensitive potassium currents, and block of these currents ablated H2O2-induced changes in RMP, input resistance and AP discharge. Following washout of H2O2 AP discharge was enhanced due to depolarization of RMP and a partially maintained hyperpolarization of THR. Hyperexcitability persisted with repeated H2O2 exposure. H2O2 effects on RMP and THR were ablated by intracellular administration of the antioxidant catalase, which was immunohistochemically identified in neurons throughout the nTS. Thus, H2O2 initially reduces excitability of nTS neurons that is followed by sustained hyperexcitability, which may play a profound role in cardiorespiratory reflexes.

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Hydrogen peroxide mobilizes Ca2+ through two distinct mechanisms in rat hepatocytes

Cited by 23 publications

References 45 publications

HMGB1 release by H2O2-induced hepatocytes is regulated through calcium overload and 58-F interference

HMGB1 release by H2O2-induced hepatocytes is regulated through calcium overload and 58-F interference

Oxidative stress enhances IL-8 and inhibits CCL20 production from intestinal epithelial cells in response to bacterial flagellin

H2O2 induces delayed hyperexcitability in nucleus tractus solitarii neurons

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