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Query: EC:3.1.4.3 (
phospholipase C
)
18,461
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Reactive oxygen species, such as the superoxide anion, H2O2, and the hydroxyl radical, have been considered as cytotoxic by-products of cellular metabolism. However, recent studies have provided evidence that H2O2 serves as a signaling molecule modulating various physiological functions. Here we investigated the effect of H2O2 on the regulation of intracellular Ca2+ signaling in rat cortical astrocytes. H2O2 triggered the generation of oscillations of intracellular Ca2+ concentration ([Ca2+]i) in a concentration-dependent manner over the range 10-100 microM. The H2O2-induced [Ca2+]i oscillations persisted in the absence of extracellular Ca2+ and were prevented by depletion of intracellular Ca2+ stores with thapsigargin. The H2O2-induced [Ca2+]i oscillations were not inhibited by pretreatment with ryanodine but were prevented by 2-aminoethoxydiphenyl borate and caffeine, known antagonists of inositol 1,4,5-trisphosphate receptors. H2O2 activated
phospholipase C
(
PLC
) gamma1 in a dose-dependent manner, and U73122, an inhibitor of
PLC
, completely abolished the H2O2-induced [Ca2+]i oscillations. In addition, RNA interference against PLCgamma1 and the expression of the inositol 1,4,5-trisphosphate-sequestering "sponge" prevented the generation of [Ca2+]i oscillations. H2O2-induced [Ca2+]i oscillations and PLC1 phosphorylation were inhibited by pretreatment with dithiothreitol, a sulfhydryl-reducing agent. Finally, epidermal growth factor induced H2O2 production, PLCgamma1 activation, and [Ca2+]i increases, which were attenuated by N-acetylcysteine and diphenyleneiodonium and by the overexpression of
peroxiredoxin
type II. Therefore, we conclude that low concentrations of exogenously applied H2O2 generate [Ca2+]i oscillations by activating PLCgamma1 through sulfhydryl oxidation-dependent mechanisms. Furthermore, we show that this mechanism underlies the modulatory effect of endogenously produced H2O2 on epidermal growth factor-induced Ca2+ signaling in rat cortical astrocytes.
...
PMID:Critical role of phospholipase Cgamma1 in the generation of H2O2-evoked [Ca2+]i oscillations in cultured rat cortical astrocytes. 1654 37
Gradually increasing atmospheric CO
2
partial pressure (pCO
2
) has caused an imbalance in carbonate chemistry and resulted in decreased seawater pH in marine ecosystems, termed seawater acidification. Anthropogenic seawater acidification is postulated to affect the physiology of many marine calcifying organisms. To understand the possible effects of seawater acidification on the proteomic responses of a marine crustacean brine shrimp (Artemia sinica) three groups of cysts were hatched and further raised in seawater at different pH levels (8.2 as control and 7.8 and 7.6 as acidification stress levels according to the predicted levels at the end of this century and next century, respectively) for 1, 7 and 14 days followed by examination of the protein expression changes via two-dimensional gel electrophoresis. Searches of protein databases revealed that 67 differential protein spots were altered due to lower pH level (7.6 and 7.8) stress in comparison to control groups (pH 8.2) by mass spectrometry. Generally, these differentially expressed proteins included the following: 1) metabolic process-related proteins involved in glycolysis and glucogenesis, nucleotide/amino acid/fatty acid metabolism, protein biosynthesis, DNA replication and apoptosis; 2) stress response-related proteins, such as
peroxiredoxin
,
thioredoxin peroxidase
, 70-kDa heat shock protein, Na/K ATPase, and ubiquinol-cytochrome c reductase; 3) immune defence-related proteins, such as prophenoloxidase and ferritin; 4) cytoskeletal-related proteins, such as myosin light chain, TCP1 subunit 2, tropomyosin and tubulin alpha chain; and 5) signal transduction-related proteins, such as
phospholipase C
-like protein, 14-3-3 zeta, translationally controlled tumour protein and RNA binding motif protein. Taken together, these data support the idea that CO
2
-driven seawater acidification may affect protein expression in the crustacean A. sinica and possibly also in other species that feed on brine shrimp in the ecosystem, particularly marine food webs.
...
PMID:Differential protein expression using proteomics from a crustacean brine shrimp (Artemia sinica) under CO
2
-driven seawater acidification. 2772 59
I learned biochemistry from P. Boon Chock and Earl Stadtman while working on the regulation of
Escherichia coli
glutamine synthetase as a postdoctoral fellow at the National Institutes of Health. After becoming a tenured scientist at the same institute, my group discovered, purified, and cloned the first three prototypical members of the
phospholipase C
family and uncovered the mechanisms by which various cell-surface receptors activate these enzymes to generate diacylglycerol and inositol 1,4,5-trisphosphate. We also discovered the family of
peroxiredoxin
(
Prx
) enzymes that catalyze the reduction of H
2
O
2
, and we established that mammalian cells express six
Prx
isoforms that not only protect against oxidative damage but also mediate cell signaling by modulating intracellular H
2
O
2
levels. To validate the signaling role of H
2
O
2
, we showed that epidermal growth factor induces a transient increase in intracellular H
2
O
2
levels, and the essential cysteine residue of protein-tyrosine phosphatases is a target for specific and reversible oxidation by the H
2
O
2
produced in such cells. These observations led to a new paradigm in receptor signaling, in which protein tyrosine phosphorylation is achieved not via activation of receptor tyrosine kinases alone but also through concurrent inhibition of protein-tyrosine phosphatases by H
2
O
2
Our studies revealed that
Prx
isozymes are extensively regulated via phosphorylation as well as by hyperoxidation of the active-site cysteine to cysteine sulfinic acid, with the reverse reaction being catalyzed by sulfiredoxin. This reversible hyperoxidation of
Prx
was further shown to constitute a universal marker for circadian rhythms in all domains of life.
...
PMID:A catalytic career: Studies spanning glutamine synthetase, phospholipase C, peroxiredoxin, and the intracellular messenger role of hydrogen peroxide. 3092 55
Dr. Sue Goo Rhee is recognized as a Redox Pioneer because he has published five articles in the field of antioxidants and redox signaling that have been cited >1000 times and 69 of his articles in this field have been cited between 100 and 1000 times. Dr. Rhee is known for his discovery of the first three prototypical members of the
phospholipase C
family, and for the discovery of the ubiquitously expressed peroxiredoxins. Peroxiredoxin catalyzes the thiol-mediated reduction of H
2
O
2
. These enzymes protect cellular molecules from oxidative damage. Importantly, they also regulate cell signaling by modulating the intracellular levels of H
2
O
2
that are induced by signaling agonists. He elucidated the mechanism by which the peroxiredoxins participate in signaling by H
2
O
2
: Dr. Rhee demonstrated that growth agonists such as epidermal growth factor induce a transient elevation of intracellular H
2
O
2
that oxidize the catalytically essential cysteine residue of protein tyrosine phosphatases. The oxidation inactivates the phosphatases, allowing enhanced protein tyrosine phosphorylation to mediate cell signaling. In addition, he established that peroxiredoxins are exquisitely regulated through phosphorylation, glutathionylation, and hyperoxidation of their active site cysteine to cysteine sulfinic acid. Dr. Rhee showed that cysteine oxidation to its sulfinic acid derivative is not irreversible as previously thought. The reduction of hyperoxidized
peroxiredoxin
is catalyzed by sulfiredoxin. His further investigations implicated cyclic hyperoxidation and reduction of
peroxiredoxin
in the regulation of certain circadian rhythms.
...
PMID:Redox Pioneer: Professor Sue Goo Rhee. 3253 32
