Showing papers by "Henry Jay Forman published in 2001"
TL;DR: The current knowledge in redox signaling is summarized, more specifically studies that are particular to macrophages are described that can activate signaling pathways resulting in a broad array of physiological responses from cell proliferation to gene expression and apoptosis.
507 citations
TL;DR: It is proposed that the GSH-dependent cytoprotective pathways induced by 15d-PGJ2 contribute to its antiatherogenic effects and that these pathways are distinct from those leading to apoptosis.
Abstract: The lipid products derived from the cyclooxygenase pathway can have diverse and often contrasting effects on vascular cell function. Cyclopentenone prostaglandins (cyPGs), such as 15-deoxy-Δ12,14-prostaglandin-J2 (15d-PGJ2), a peroxisome proliferator–activated receptor-γ (PPARγ) agonist, have been reported to cause endothelial cell apoptosis, yet in other cell types, cyPGs induce cytoprotective mediators, such as heat shock proteins, heme oxygenase-1, and glutathione (GSH). Herein, we show in human endothelial cells that low micromolar concentrations of 15d-PGJ2 enhance GSH-dependent cytoprotection through the upregulation of glutamate-cysteine ligase, the rate-limiting enzyme of GSH synthesis, as well as GSH reductase. The effect of 15d-PGJ2 on GSH synthesis is attributable to the cyPG structure but is independent of PPAR, inasmuch as the other cyPGs, but not PPARγ or PPARα agonists, are able to increase GSH. The increase in cellular GSH is accompanied by abrogation of the proapoptotic effects of 4-hydro...
151 citations
TL;DR: This brief review suggests that: 1) hydrogen peroxide and superoxide, but not the hydroxyl radical, function as second messengers; 2) antioxidant enzymes function in the “turn‐off” phase of signal transduction; 3) the chemistry of thiols is critical in redox signaling; and 4) the primary physiological role of the respiratory burst in macrophages may be inredox signaling rather than microbicidal activity.
Abstract: During phagocytosis or stimulation with a wide variety of agents, macrophages and other phagocytic cells produce reactive oxygen species (ROS) through activation of a multicomponent NADPH oxidase. ROS production through related NADPH oxidases has recently been demonstrated in several other cell types. Furthermore, the physiological generation of ROS production has now been clearly implicated in activating signaling pathways resulting in a broad array of physiological responses from cell proliferation to gene expression and apoptosis. This brief review suggests that: 1) hydrogen peroxide and superoxide, but not the hydroxyl radical, function as second messengers; 2) antioxidant enzymes function in the "turn-off" phase of signal transduction; 3) the chemistry of thiols is critical in redox signaling; and 4) the primary physiological role of the respiratory burst in macrophages may be in redox signaling rather than microbicidal activity.
110 citations
TL;DR: It is demonstrated that glutathione efflux is associated with apical chloride secretion, not with the CF transmembrane conductance regulator per se, and the defect of glutathion efflux in CF can be overcome pharmacologically.
Abstract: Cystic fibrosis (CF), an inherited disease characterized by defective epithelial Cl−transport, damages lungs via chronic inflammation and oxidative stress. Glutathione, a major antioxidant in the e...
56 citations
TL;DR: It is demonstrated that L2 cells maintain the same responsiveness to oxidant challenge as do primary cultured AT2 cells in terms of increasing GSH synthetic capacity, and that different pathways are involved in the induction of two GCS subunits by 4HNE.
Abstract: Previous studies from this laboratory demonstrated that 4-hydroxy-2-nonenal (4HNE), a lipid peroxidation product, induces expression of γ -glutamylcysteine synthetase (GCS), the rate-limiting enzyme in de novo glutathione (GSH) synthesis, in rat alveolar epithelial L2 cells. The present study demonstrates that 4HNE also induces GCS in primary cultured alveolar epithelial type II (AT2) cells. Enzyme activity, protein content, and messenger RNA levels of both the catalytic (GCS-HS) and regulatory (GCS-LS) subunits were significantly increased in AT2 cells treated with 5 or 10 μ M 4HNE, the same concentrations that induced GCS expression in L2 cells. As in L2 cells, 4HNE induced a greater AT2-cell increase in GCS-LS than in GCS-HS, suggesting that modulation of GCS-LS may play a dominant role in regulating GSH concentration in response to oxidative stress. Additional studies using mitogen-activated protein kinase pathway inhibitors showed that induction by 4HNE of GCS-HS, but not GCS-LS, was mediated through...
54 citations
TL;DR: Whether chlorzoxazone or 1-EBIO altered ion transport across Delta F508-CF transmembrane conductance regulator homozygous CFT1 airway cells was determined and alterations in basolateral G(K) alone can modulate epithelial Na(+) transport.
Abstract: Previous studies demonstrated that chlorzoxazone or 1-ethyl-2-benzimidazolinone (1-EBIO) enhances transepithelial Cl− secretion by increasing basolateral K+ conductance (G K) (Singh AK, Devor DC, G...
25 citations
TL;DR: This study demonstrates that the receptor for ADP in rat AM is not coupled to the ERK and AKT pathways and, that neither the ERk pathway nor AKT is essential to induce the activation of the NAPDH oxidase by ADP by rat AM while tyrosine kinases appeared to be required.
18 citations
TL;DR: This unit describes protocols for characterizing the expression of two glutathione biosynthesis enzymes: gamma‐glutamylcysteine synthase (GCS) and gamma‐ GLUTamyl transpeptidase (GGT) in response to oxidants.
Abstract: This unit describes protocols for characterizing the expression of two glutathione biosynthesis enzymes: gamma-glutamylcysteine synthase (GCS) and gamma-glutamyl transpeptidase (GGT) in response to oxidants. GCS catalyzes the first and rate-limiting step of glutathione synthesis, while GGT degrades extracellular glutathione (GSH) to provide the amino acids required for intracellular synthesis of GSH. Northern blot hybridization is used to quantitatively assess the mRNAs for the two enzymes in response to oxidant. Nuclear run-on is used to determine the rate of transcription.
2 citations
Journal Article•
2 citations
TL;DR: It is shown that the anti-inflammatory effects of high doses of acetylsalicylic acid in lung epithelial cells include inhibition of interleukin (IL)-1β- and tumor necrosis factor (TNF)
Abstract: in this issue of the American Journal of Physiology-Lung Cellular and Molecular Physiology , Yoo et al. ([17][1]) show that the anti-inflammatory effects of high doses of acetylsalicylic acid (ASA) in lung epithelial cells include inhibition of interleukin (IL)-1β- and tumor necrosis factor (TNF