fabian moraga | UNIVER MILENIUM (original) (raw)

Papers by fabian moraga

Research paper thumbnail of Lateral forces on spheres in turbulent uniform shear flow

International Journal of Multiphase Flow, 1999

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Activation of Primary Human Monocytes by the Oxidized Form of alpha 1Antitrypsin

Journal of Biological Chemistry, 2000

The oxidation of methionine residues in many proteins, including the serine proteinase inhibitor ... more The oxidation of methionine residues in many proteins, including the serine proteinase inhibitor alpha1-antitrypsin (AAT), can result in functional inactivation. In this study we investigated the pro-inflammatory properties of oxidized AAT (oxAAT), specifically its ability to activate human monocytes in culture. Monocytes stimulated with oxAAT at concentrations up to 0.2 mg/ml for 24 h showed significant elevation in monocyte chemoattractant protein-1, cytokine interleukin-6, and tumor necrosis factor-alpha expression and increased NADPH oxidase activity. Monocytes activated with oxAAT showed surprising effects on lipid metabolism. Expression of low density lipoprotein (LDL) receptors increased by up to 76% compared with controls but was not accompanied by any changes in (125)I-labeled LDL binding and, paradoxically, decreased LDL uptake, degradation, and intracellular cholesterol synthesis. oxAAT also down-regulated the scavenger receptor CD36, which takes up and is up-regulated by oxidized LDL and is down-regulated by cholesterol efflux. As a by-product of oxidative events accompanying inflammation, oxAAT has multiple effects on cytokine expression, generation of reactive oxygen species, and on intracellular lipid metabolism. The up-regulation of monocyte-derived reactive oxygen by oxAAT could potentially result in self-amplification of AAT oxidation and, thereby, the other effects deriving from it. This implies that there are as yet unidentified regulatory processes that control this cycle.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of The Carboxyl-Terminal Fragment of α1Antitrypsin Is Present in Atherosclerotic Plaques and Regulates Inflammatory Transcription Factors in Primary Human Monocytes

Molecular Cell Biology Research Communications, 2000

alpha1-Antitrypsin (AAT) serine proteinase inhibitor is found in most biological fluids, diffuses... more alpha1-Antitrypsin (AAT) serine proteinase inhibitor is found in most biological fluids, diffuses into most tissues, and is an important factor in controlling tissue damage by proteases in inflammatory diseases such as atherosclerosis. We have previously reported that the C-terminal fragment (C-36) generated during the cleavage of AAT by proteinases forms amyloid fibrils which have biological effects unrelated to precursor functions. Here we show that the C-36 fragment is present in atherosclerotic plaques, particularly within the fibrous cap at the base of the lipid core. We also found that human monocyte stimulation with C-36 fibrils led to a strong activation of both peroxisome proliferator-activated receptors alpha and gamma (PPARalpha and PPARgamma) at 1, 2, and 18 h of cell culture. A parallel increase in the intracellular lipid accumulation was also observed. Furthermore, stimulation of monocytes with C-36 for 18 h led to activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) activation. These data for the first time demonstrate the peptide of AAT as a component of atherosclerotic plaques and as a novel activator of PPARalpha, PPARgamma, NF-kappaB, and AP-1 in cultured monocytes. Taken together, the effects of the peptide represent a new mechanism of monocyte activation that may be of importance not only in atherogenesis, but also in other inflammatory processes.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Effects of Noninhibitory α-1Antitrypsin on Primary Human Monocyte Activation in Vitro

Archives of Biochemistry and Biophysics, 2001

Bookmarks Related papers MentionsView impact

Research paper thumbnail of C-terminal fragment of α1-antitrypsin activates human monocytes to a pro-inflammatory state through interactions with the CD36 scavenger receptor and LDL receptor

Atherosclerosis, 2001

Bookmarks Related papers MentionsView impact

Research paper thumbnail of esfera emocional y su relacion proceso aprendizaje

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Lateral forces on spheres in turbulent uniform shear flow

International Journal of Multiphase Flow, 1999

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Activation of Primary Human Monocytes by the Oxidized Form of alpha 1Antitrypsin

Journal of Biological Chemistry, 2000

The oxidation of methionine residues in many proteins, including the serine proteinase inhibitor ... more The oxidation of methionine residues in many proteins, including the serine proteinase inhibitor alpha1-antitrypsin (AAT), can result in functional inactivation. In this study we investigated the pro-inflammatory properties of oxidized AAT (oxAAT), specifically its ability to activate human monocytes in culture. Monocytes stimulated with oxAAT at concentrations up to 0.2 mg/ml for 24 h showed significant elevation in monocyte chemoattractant protein-1, cytokine interleukin-6, and tumor necrosis factor-alpha expression and increased NADPH oxidase activity. Monocytes activated with oxAAT showed surprising effects on lipid metabolism. Expression of low density lipoprotein (LDL) receptors increased by up to 76% compared with controls but was not accompanied by any changes in (125)I-labeled LDL binding and, paradoxically, decreased LDL uptake, degradation, and intracellular cholesterol synthesis. oxAAT also down-regulated the scavenger receptor CD36, which takes up and is up-regulated by oxidized LDL and is down-regulated by cholesterol efflux. As a by-product of oxidative events accompanying inflammation, oxAAT has multiple effects on cytokine expression, generation of reactive oxygen species, and on intracellular lipid metabolism. The up-regulation of monocyte-derived reactive oxygen by oxAAT could potentially result in self-amplification of AAT oxidation and, thereby, the other effects deriving from it. This implies that there are as yet unidentified regulatory processes that control this cycle.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of The Carboxyl-Terminal Fragment of α1Antitrypsin Is Present in Atherosclerotic Plaques and Regulates Inflammatory Transcription Factors in Primary Human Monocytes

Molecular Cell Biology Research Communications, 2000

alpha1-Antitrypsin (AAT) serine proteinase inhibitor is found in most biological fluids, diffuses... more alpha1-Antitrypsin (AAT) serine proteinase inhibitor is found in most biological fluids, diffuses into most tissues, and is an important factor in controlling tissue damage by proteases in inflammatory diseases such as atherosclerosis. We have previously reported that the C-terminal fragment (C-36) generated during the cleavage of AAT by proteinases forms amyloid fibrils which have biological effects unrelated to precursor functions. Here we show that the C-36 fragment is present in atherosclerotic plaques, particularly within the fibrous cap at the base of the lipid core. We also found that human monocyte stimulation with C-36 fibrils led to a strong activation of both peroxisome proliferator-activated receptors alpha and gamma (PPARalpha and PPARgamma) at 1, 2, and 18 h of cell culture. A parallel increase in the intracellular lipid accumulation was also observed. Furthermore, stimulation of monocytes with C-36 for 18 h led to activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) activation. These data for the first time demonstrate the peptide of AAT as a component of atherosclerotic plaques and as a novel activator of PPARalpha, PPARgamma, NF-kappaB, and AP-1 in cultured monocytes. Taken together, the effects of the peptide represent a new mechanism of monocyte activation that may be of importance not only in atherogenesis, but also in other inflammatory processes.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Effects of Noninhibitory α-1Antitrypsin on Primary Human Monocyte Activation in Vitro

Archives of Biochemistry and Biophysics, 2001

Bookmarks Related papers MentionsView impact

Research paper thumbnail of C-terminal fragment of α1-antitrypsin activates human monocytes to a pro-inflammatory state through interactions with the CD36 scavenger receptor and LDL receptor

Atherosclerosis, 2001

Bookmarks Related papers MentionsView impact

Research paper thumbnail of esfera emocional y su relacion proceso aprendizaje

Bookmarks Related papers MentionsView impact