Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phospholipase C-gamma1 plays a central role in signal transduction, and it is important in cellular growth, differentiation, and proliferation. Human cholesteatoma in the middle ear is characterized by the presence of a keratinizing epithelium that is believed to have hyperproliferative properties. The purpose of this study is to elucidate the distribution of phospholipase C-gamma1 in cholesteatoma matrix and deep meatal skin with Western blot analysis and immunohistochemistry. In conclusion, overexpression of phospholipase C-gamma1 in cholesteatoma matrix suggests a possible derangement of enhanced growth signal transduction in keratinocytes.
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PMID:Signal transduction pathway in human middle ear cholesteatoma. 1035 47

Fluid-free alveolar space is critical for normal gas exchange. Influenza virus alters fluid transport across respiratory epithelia producing rhinorrhea, middle ear effusions, and alveolar flooding. However, the mechanism of fluid retention remains unclear. We investigated influenza virus strain A/PR/8/34, which can attach and enter mammalian cells but is incapable of viral replication and productive infection in mammalian epithelia, on epithelial sodium channels (ENaC) in rat alveolar type II (ATII) cells. In parallel, we determined the effects of virus on amiloride-sensitive (i.e., ENaC-mediated) fluid clearance in rat lungs in vivo. Although influenza virus did not change the inulin permeability of ATII monolayers, it rapidly reduced the net volume transport across monolayers. Virus reduced the open probability of single ENaC channels in apical cell-attached patches. U-73122, a phospholipase C (PLC) inhibitor, and PP2, a Src inhibitor, blocked the effect of virus on ENaC. GF-109203X, a protein kinase C (PKC) inhibitor, also blocked the effect, suggesting a PKC-mediated mechanism. In parallel, intratracheal administration of influenza virus produced a rapid inhibition of amiloride-sensitive (i.e., ENaC-dependent) lung fluid transport. Together, these results show that influenza virus rapidly inhibits ENaC in ATII cells via a PLC- and Src-mediated activation of PKC but does not increase epithelial permeability in this same rapid time course. We speculate that this rapid inhibition of ENaC and formation of edema when the virus first attaches to the alveolar epithelium might facilitate subsequent influenza infection and may exacerbate influenza-mediated alveolar flooding that can lead to acute respiratory failure and death.
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PMID:Influenza virus inhibits ENaC and lung fluid clearance. 1512 35

Recent reports have shown that cytokines inhibit fluid absorption by suppressing Na(+) channel activity in various epithelia. In this study, we investigated the role of epithelial sodium channel (ENaC) in fluid absorption in normal human middle ear epithelial (NHMEE) cells, as well as the effects of Interleukin (IL)-1beta on ENaC expression and fluid absorption in NHMEE cells. We confirmed that ENaC alpha, beta and gamma were predominantly expressed on the apical surface of the NHMEE cells by immunocytochemistry. Addition of amiloride, a potent ENaC blocker, to apical membranes of NHMEE cells decreased the fluid absorption rate in a dose-dependent manner. Treatment with 10 ng/ml IL-1beta for 24 h suppressed ENaC beta expression, the ENaC-dependent short-circuit current (Isc), and ENaC-dependent fluid absorption. When the NHMEE cells were pretreated with a phospholipase C (PLC)inhibitor (U73122, 10 microM), a protein kinase C (PKC) inhibitor (Calphostin C, 0.1 microM), or extracellular signal regulated kinase (ERK) 1/2 inhibitor (PD98059, 10 microM), the amiloride-sensitive currents in IL-1beta-treated cells were reversed to control levels; an effect not seen with SB202190 (an inhibitor of p38 mitogen-activated protein (MAP) kinase) or SP600125 (a reversible inhibitor of c-Jun N-terminal kinase). In this study we showed that ENaC is essential for fluid absorption in NHMEE cells and that IL-1beta suppresses the ENaC-dependent current via the PLC-PKC-ERK1/2 pathway. These results suggest that IL-1beta may contribute to fluid retention in otitis media with effusion by changing electrolyte transport and reducing middle ear epithelial fluid absorption.
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PMID:Interleukin-1beta suppresses epithelial sodium channel beta-subunit expression and ENaC-dependent fluid absorption in human middle ear epithelial cells. 1749 39