Biomedical subjects

Mingyi Chen

Publications and source records attributed to Mingyi Chen.

14 recordsLinked to original sources

PubMed2007

Blind phase shift estimation in phase-shifting interferometry.

A blind phase shift estimation algorithm that allows simultaneous calculation of phases and phase shifts from three or more interferograms is presented. In phase-shifting interferometry, the phase shift errors introduce specific correlations between the calculated background intensity distribution and the fringe component. These correlations can be measured with a cross-power spectrum. By minimization of an objective function based on this cross-power spectrum, the actual phase shifts are estimated and used for phase recovery. The validity of this algorithm is verified by both the numerical simulation and the experiment results.

Algorithms↗

PubMed2006

Least-squares fitting of carrier phase distribution by using a rational function in fringe projection profilometry [corrected].

A least-squares fitting technique for the carrier phase component in fringe projection profilometry is presented. The carrier phase distribution for an arbitrary measurement system can be perfectly described with a rational function, whose coefficients can be estimated by least-squares fitting to the measured reference phases, so that the restrictions and limitations in the existing techniques are eliminated.

Journal Article↗

PubMed2006

Phosphorylation of the liver X receptors.

The liver X receptors (LXRs) function as nutritional sensors for cholesterol and have important roles in lipid metabolism, glucose homeostasis, and inflammation. We provide the first evidence that LXRs are phosphorylated proteins. Mutational analysis and metabolic labeling indicate LXRalpha is phosphorylated on serine 198 in the hinge region. This is a consensus target for the MAPK family. A phosphorylation-deficient mutant, LXRalpha S198A, remains nuclear and responds to ligands like the wild-type protein. The biological significance of LXR phosphorylation remains to be elucidated but could provide a novel mechanism for the regulation of LXR signaling pathways and cellular metabolism.

Animals↗

PubMed2005

Identification and characterization of two alternatively spliced transcript variants of human liver X receptor alpha.

The liver X receptor alpha (LXRalpha) is a member of the nuclear hormone receptor superfamily that plays an important role in lipid homeostasis. Here we characterize two alternative human LXRalpha transcripts, designated LXRalpha2 and LXRalpha3. All three LXRalpha isoforms are derived from the same gene via alternative splicing and differential promoter usage. The LXRalpha2 isoform lacks the first 45 amino acids of LXRalpha1, and is generated through the use of a novel promoter and first exon. LXRalpha3 lacks 50 amino acids within the ligand binding domain and is generated through alternative recognition of the 3'-splice site in exon 6. LXRalpha2 and LXRalpha3 are expressed at lower levels compared with LXRalpha1 in most tissues, except that LXRalpha2 expression is dominant in testis. Both LXRalpha2 and LXRalpha3 heterodimerize with the retinoid X receptor and bind to LXR response elements. LXRalpha2 shows reduced transcriptional activity relative to LXRalpha1, indicating that the N-terminal domain of LXRalpha is essential for its full transcriptional activity. LXRalpha3 is unable to bind ligand and is transcriptionally inactive. These observations outline a previously unrecognized role for the N terminus in LXR function and suggest that the expression of alternative LXRalpha transcripts in certain biological contexts may impact LXR signaling and lipid metabolism.

Alternative Splicing↗

PubMed2005

Least-squares algorithm for phase-stepping interferometry with an unknown relative step.

A pointwise least-squares phase-stepping algorithm with an unknown relative phase step is proposed. In phase-stepping interferometry the recorded temporal intensity sequence is a discrete sinusoidal signal biased by a direct-current component. Its value at a certain time can be predicted from its three past samples by use of a recursive formula. Based on this linear prediction property, an unbiased least-squares estimator is deduced to determine the relative phase step from a sequence of intensity values, and the result is used to evaluate the phase value. The validity and performance of this algorithm are verified by computer simulations.

Journal Article↗

PubMed2005

Induction of NR4A orphan nuclear receptor expression in macrophages in response to inflammatory stimuli.

Oxidized lipids and inflammatory cytokines are believed to play a causal role in atherosclerosis through the regulation of gene expression in macrophages and other cells. Previous work has implicated the nuclear receptors peroxisome proliferator-activated receptor and liver X receptor in the control of lipid-dependent gene expression and inflammation. Here we demonstrate that expression of a third group of nuclear receptors, the NR4A ligand-independent orphan receptors, is highly inducible in macrophages by diverse inflammatory stimuli. Treatment of macrophages with lipopolysaccharide (LPS), cytokines, or oxidized lipids triggers the transcriptional induction of Nur77 (NR4A1), Nurr1 (NR4A2), and NOR1 (NR4A3) expression. Several lines of evidence point to the NF-kappaB signaling pathway as a principal mediator of inducible NR4A expression in macrophages. Analysis of the murine and human Nur77 promoters revealed two highly conserved NF-kappaB response elements. Mutation of these elements inhibited LPS-dependent expression of the Nur77 promoter in transient transfection assays. Furthermore, induction of Nur77 expression by LPS was severely compromised in fibroblasts lacking the three NF-kappaB subunits, Nfkb1, c-Rel, and RelA. Consistent with its ability to be induced by oxidized lipids, Nur77 was expressed in macrophages within human atherosclerotic lesions. These results identified NR4A nuclear receptors as potential transcriptional mediators of inflammatory signals in activated macrophages.

Animals↗

PubMed2005

A role for the apoptosis inhibitory factor AIM/Spalpha/Api6 in atherosclerosis development.

Macrophages play a central role in the development of atherosclerosis through the accumulation of oxidized LDL (oxLDL). AIM (Spalpha/Api6) has previously been shown to promote macrophage survival; however, its function in atherogenesis is unknown. Here we identify AIM as a critical factor that protects macrophages from the apoptotic effects of oxidized lipids. AIM protein is induced in response to oxLDL loading and is highly expressed in foam cells within atherosclerotic lesions. Interestingly, both expression of AIM in lesions and its induction by oxidized lipids require the action of LXR/RXR heterodimers. AIM-/- macrophages are highly susceptible to oxLDL-induced apoptosis in vitro and undergo accelerated apoptosis in atherosclerotic lesions in vivo. Moreover, early atherosclerotic lesions in AIM-/-LDLR-/- double knockout mice are dramatically reduced when compared to AIM+/+LDLR-/- controls. We conclude that AIM production facilitates macrophage survival within atherosclerotic lesions and that loss of AIM decreases early lesion development by increasing macrophage apoptosis.

Animals↗

PubMed2005

Essential role of cytoplasmic sequences for cell-surface sorting of the lectin-like oxidized LDL receptor-1 (LOX-1).

Lectin-like oxidized LDL receptor-1 (LOX-1) is an oxidized low-density lipoprotein (OxLDL) receptor found in endothelial cells and a member of the natural killer (NK) receptor gene complex. Here, we demonstrate that the ability of LOX-1 binding to OxLDL distinguishes it from other NK receptors. Domain swapping of the lectin-like domain between LOX-1 and the NK cell receptors CD94, NKG2D, and LY-49A demonstrated the crucial role of this domain for recognition of OxLDL by LOX-1, but not for the correct cell-surface sorting of LOX-1. Using LOX-1 GFP fusion constructs, we find that the combination of cytoplasmic and transmembrane domains of LOX-1 is sufficient to target the chimeric protein to the cell-surface. Using N-terminal deletions we determined that the correct cell-surface localization is dependent on a positively charged motif present in the cytosolic juxtamembrane region of LOX-1. Furthermore, the extracellular localization of the LOX-1 C-terminus is disrupted when we mutated the cytoplasmic basic amino acids, Lys-22, Lys-23 and Lys-25 to Glu. Collectively, these results indicate that the N-terminal cytoplasmic domain of LOX-1 determines the correct expression of the lectin domain on the cell-surface.

Amino Acid Motifs↗

PubMed2004

Gamma correction for digital fringe projection profilometry.

Digital fringe projection profilometry utilizes a digital video projector as a structured light source and thus gains great flexibility. However, the gamma nonlinearity of the video projector inevitably decreases the accuracy and resolution of the measurement. We propose a gamma-correction technique based on statistical analysis of the fringe images. The technique allows one to estimate the value of gamma from the normalized cumulative histogram of the fringe images. By iterating the two steps, gamma estimation and phase evaluation, the actual gamma value can be calculated. At the same time the phase distribution of the fringe pattern can be solved with higher accuracy. In so doing, neither photometric calibration nor knowledge of the device is required. Both computer simulation and experiment are carried out to demonstrate the validity of this technique.

Journal Article↗

PubMed2003

The phospholipid transfer protein gene is a liver X receptor target expressed by macrophages in atherosclerotic lesions.

The liver X receptors (LXRs) are members of the nuclear receptor superfamily that are activated by oxysterols. In response to ligand binding, LXRs regulate a variety of genes involved in the catabolism, transport, and uptake of cholesterol and its metabolites. Here we demonstrate that LXRs also regulate plasma lipoprotein metabolism through control of the phospholipid transfer protein (PLTP) gene. LXR ligands induce the expression of PLTP in cultured HepG2 cells and mouse liver in vivo in a coordinate manner with known LXR target genes. Moreover, plasma phospholipid transfer activity is increased in mice treated with the synthetic LXR ligand GW3965. Unexpectedly, PLTP expression was also highly inducible by LXR in macrophages, a cell type not previously recognized to express this enzyme. The ability of synthetic and oxysterol ligands to regulate PLTP mRNA in macrophages and liver is lost in animals lacking both LXRalpha and LXRbeta, confirming the critical role of these receptors. We further demonstrate that the PLTP promoter contains a high-affinity LXR response element that is bound by LXR/RXR heterodimers in vitro and is activated by LXR/RXR in transient-transfection studies. Finally, immunohistochemistry studies reveal that PLTP is highly expressed by macrophages within human atherosclerotic lesions, suggesting a potential role for this enzyme in lipid-loaded macrophages. These studies outline a novel pathway whereby LXR and its ligands may modulate lipoprotein metabolism.

Animals↗

PubMed2002

LOX-1 expressed in cultured rat chondrocytes mediates oxidized LDL-induced cell death-possible role of dephosphorylation of Akt.

The oxidative changes of lipids in cartilage proceed with ageing and with the grade of osteoarthritis. To clarify the role of oxidatively modified lipids in articular cartilage in osteoarthritis, here, we investigated lectin-like oxidized LDL receptor (LOX-1) in rat cultured articular chondrocytes. LOX-1 expression was detectable in basal culture condition and enhanced by the treatment of oxidized LDL and interleukin-1beta. DiI-labeled oxidized LDL was bound and ingested by chondrocytes via LOX-1. Oxidized LDL dose-dependently reduced chondrocyte viability, inducing non-apoptotic cell death, which was again suppressed by anti-LOX-1 antibody treatment. Oxidized LDL reduced the amount of phosphorylated Akt, a substrate of PI3 kinase via LOX-1. Consistently, the PI3 kinase inhibitor, LY294002, decreased cell viability dose-dependently, and the PI3 kinase activator, IGF-I, reversed the effect of oxidized LDL on the cell death. LOX-1 might be involved in the pathogenesis of osteoarthritis, inducing chondrocyte death through PI3 kinase/Akt pathway.

Animals↗

PubMed2002

Synthetic LXR ligand inhibits the development of atherosclerosis in mice.

The nuclear receptors LXRalpha and LXRbeta have been implicated in the control of cholesterol and fatty acid metabolism in multiple cell types. Activation of these receptors stimulates cholesterol efflux in macrophages, promotes bile acid synthesis in liver, and inhibits intestinal cholesterol absorption, actions that would collectively be expected to reduce atherosclerotic risk. However, synthetic LXR ligands have also been shown to induce lipogenesis and hypertriglyceridemia in mice, raising questions as to the net effects of these compounds on the development of cardiovascular disease. We demonstrate here that the nonsteroidal LXR agonist GW3965 has potent antiatherogenic activity in two different murine models. In LDLR(-/-) mice, GW3965 reduced lesion area by 53% in males and 34% in females. A similar reduction of 47% was observed in male apoE(-/-) mice. Long-term (12-week) treatment with LXR agonist had differential effects on plasma lipid profiles in LDLR(-/-) and apoE(-/-) mice. GW3965 induced expression of ATP-binding cassettes A1 and G1 in modified low-density lipoprotein-loaded macrophages in vitro as well as in the aortas of hyperlipidemic mice, suggesting that direct actions of LXR ligands on vascular gene expression are likely to contribute to their antiatherogenic effects. These observations provide direct evidence for an atheroprotective effect of LXR agonists and support their further evaluation as potential modulators of human cardiovascular disease.

Animals↗

PubMed2002

Lectin-like oxidized low-density lipoprotein receptor 1 mediates leukocyte infiltration and articular cartilage destruction in rat zymosan-induced arthritis.

OBJECTIVE: The relationship between rheumatoid arthritis and atherosclerosis has been recognized for >20 years. This study aimed to elucidate the roles of oxidized low-density lipoprotein (ox-LDL; one of the main pathogenic factors of atherosclerosis) and its endothelial receptor, lectin-like ox-LDL receptor 1 (LOX-1), in arthritic joints using a rat zymosan-induced arthritis (ZIA) model. METHODS: LOX-1 expression and ox-LDL accumulation in arthritic joints were detected by immunohistochemistry using specific mouse anti-LOX-1 and anti-ox-LDL monoclonal antibodies, respectively. To elucidate the effects of the expressed LOX-1 on arthritis, ZIA rats were treated with anti-LOX-1 antibody or normal mouse IgG. The severity of arthritis was analyzed by joint swelling. Cell infiltration, synovial hyperplasia, and proteoglycan losses were also determined by histologic scoring. Proinflammatory cytokine and nitrite levels in serum and joint fluid were also measured. RESULTS: Immunohistochemical study of ZIA demonstrated LOX-1 expression on synovial endothelium and postcapillary venules at 6 hours after the induction of inflammation, with maximum expression detected at 24 hours. LOX-1 was also expressed weakly on both joint cartilage and synovium. Ox-LDL, a ligand of LOX-1, was also detected in articular chondrocytes. Administration of anti-LOX-1 antibody, which blocks LOX-1 activity, suppressed joint swelling (by 33.5%), leukocyte infiltration, and joint nitrite accumulation at 24 hours, as well as cartilage destruction at 7 days, compared with control rats. CONCLUSION: LOX-1 induction in arthritic joints might play a role in promoting joint inflammation and cartilage destruction by mediating leukocyte infiltration into the arthritic joints of ZIA rats.

Animals↗

PubMed2002

LOX-1, the receptor for oxidized low-density lipoprotein identified from endothelial cells: implications in endothelial dysfunction and atherosclerosis.

Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) was initially identified as the major receptor for oxidized LDL (OxLDL) in endothelial cells. Its inducible expression in macrophages and smooth muscle cell was also observed. LOX-1 is a Type II membrane protein with a typical C-type lectin structure at the extracellular C-terminus. It can be cleaved by an unknown protease at the extracellular juxtamembrane region to release the soluble form of LOX-1. The extracellular domains of LOX-1 are post-translationally modified by N-linked glycosylation. Mutagenesis studies revealed that the lectin domain of LOX-1 is the functional domain that recognizes the LOX-1 ligand. The C-terminal end residues and several conserved positively charged residues spanning the lectin domain are essential for OxLDL binding. LOX-1 activation by OxLDL causes endothelial changes that are characterized by activation of nuclear factor-kappaB through an increased reactive oxygen species, subsequent induction of adhesion molecules, and endothelial apoptosis. In vitro, expression of LOX-1 is induced by many inflammatory cytokines, oxidative stress, hemodynamic stimuli, and OxLDL. In vivo, the expression is enhanced in pro-atherogenic settings including, hypertension, hyperlipidemia, and diabetes, and, indeed, is accumulated in the atherosclerotic and glomerulosclerotic lesions. LOX-1 binds multiple classes of ligands that are implicated in the pathogenesis of atherosclerosis. Besides OxLDL, LOX-1 can recognize apoptotic/aged cells, activated platelets, and bacteria, implying versatile physiological functions. Taken together, all these findings support the possible contribution of LOX-1 to the pathogenesis of vascular disorders, particularly atherosclerosis. Development of antagonists for LOX-1 might be a good therapeutic approach to vascular diseases.

Amino Acid Sequence↗