Lee-Young Chau

• PhD
• Professor at Academia Sinica

Background The accumulation of lipid-laden macrophages, foam cells, within sub-endothelial intima is a key feature of early atherosclerosis. Siglec-E, a mouse orthologue of human Siglec-9, is a sialic acid binding lectin predominantly expressed on the surface of myeloid cells to transduce inhibitory signal via recruitment of SH2-domain containing p...

Objective: Abdominal aortic aneurysm (AAA) is a vascular degenerative disease causing sudden rupture of aorta and significant mortality in elders. Nevertheless, no prognostic and therapeutic target is available for disease management. Gal-1 (galectin-1) is a β-galactoside-binding lectin constitutively expressed in vasculature with roles in maintai...

The accumulation of lipid‐laden macrophages, foam cells, within sub‐endothelial intima is a key feature of early atherosclerosis. Siglec‐E is a member of sialic acid binding lectin predominantly expressed on myeloid cells to transduce inhibitory signal upon interacting with its ligands. Whether Siglec‐E expression on macrophages impacts foam cell f...

Signal peptide peptidase (SPP) is an endoplasmic reticulum (ER)-resident aspartyl protease mediating intramembrane cleavage of type II transmembrane proteins. Increasing evidence has supported the role of SPP in ER-associated protein degradation. In the present study, we show that SPP expression is highly induced in human lung and breast cancers an...

Background Heme oxygenase (HO) catalyzes NADPH-dependent degradation of heme to liberate iron, carbon monoxide and biliverdin. The interaction between HO and cytochrome P450 reductase (CPR), an electron donor, is essential for HO activity. HO-1 is a stress-inducible isoform whereas HO-2 is constitutively expressed. HO-1 induction is commonly seen i...

Background Vascular smooth muscle cell (VSMC) migration play a key role in the development of atherosclerosis and restenosis. Galectin‐1 (Gal‐1) is a galactose‐binding lectin highly expressed in VSMCs. Previous studies have shown that Gal‐1 binds to extracellular matrix and β1integrin. Whether Gal‐1 influences VSMC motility via regulating focal adh...

Vascular smooth muscle cell (VSMC) migration play a key role in the development of intimal hyperplasia and atherosclerosis. Galectin-1 (Gal-1) is a redox-sensitive β-galactoside-binding lectin expressed in VSMCs with intracellular and extracellular localizations. Here we show that VSMCs deficient in Gal-1 (Gal-1-KO) exhibited greater motility than...

Overexpression of heme oxygenase-1 (HO-1), an endoplasmic reticulum-anchored enzyme, is observed in many cancers. HO-1 nuclear translocation has been shown to correlate with progression of several cancers. We recently reported that HO-1 is susceptible to intramembrane proteolysis and translocates to the nucleus to promote cancer growth and invasive...

In patients who survive myocardial infarction, many go on to develop congestive heart failure (CHF). Despite ongoing efforts to develop new approaches for postinfarction therapy, there are still no effective therapeutic options available to CHF patients. Currently, the delivery of cardioprotective drugs relies entirely on passive uptake via the enh...

Heme oxygenase-1 (HO-1) is a rate-limiting enzyme catalyzing oxidative degradation of cellular heme to liberate free iron, carbon monoxide (CO) and biliverdin in mammalian cells. In addition to its primary role in heme catabolism, HO-1 exhibits anti-oxidative and anti-inflammatory functions via the actions of biliverdin and CO, respectively. HO-1 i...

Endoplasmic reticulum (ER) stress is implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). TRC8 is an ER-resident E3 ligase with roles in modulating lipid and protein biosynthesis. In this study we showed that TRC8 expression was downregulated in steatotic livers of patients and mice fed with high fat diet (HFD) or methionine...

Heme oxygenase-1 (HO-1) is a heme degradation enzyme with antioxidant and immune-modulatory functions. HO-1 promotes tumorigenesis by enhancing tumor cell proliferation and invasion. Whether HO-1 has an effect on cancer progression through stromal compartments is less clear. Here we show that the growth of tumor engrafted subcutaneously in syngenei...

Heme oxygenase-1 (HO-1) is a heme-degrading enzyme anchored in the endoplasmic reticulum by a carboxyl-terminal transmembrane segment (TMS). HO-1 is highly expressed in various cancers and its nuclear localization is associated with the progression of some cancers. Nevertheless, the mechanism underlying HO-1 nuclear translocation and its pathologic...

Objective: Increased cardiac stromal cell-derived factor-1α (SDF-1α) expression promotes neovascularization and myocardial repair after ischemic injury through recruiting stem cells and reducing cardiomyocyte death. Previous studies have shown that heme oxygenase-1 and its reaction byproduct, carbon monoxide (CO), induce SDF-1α expression in ische...

Heme oxygenase-1 (HO-1) is a stress-responsive enzyme with potent anti-oxidant and anti-inflammatory activities. Previous studies have shown that systemic induction of HO-1 by chemical inducers reduces adiposity and improves insulin sensitivity. To dissect the specific function of HO-1 in adipose tissue, we generated transgenic mice with adipose HO...

Increased adipose tissue macrophages contribute to obesity-induced metabolic syndrome. Heme oxygenase-1 (HO-1) is a stress-inducible enzyme with potent anti-inflammatory and proangiogenic activities in macrophages. However, the role of macrophage HO-1 on obesity-induced adipose inflammation and metabolic syndrome remains unclear. Here we show that...

Effect of HFD on adipocyte hypertrophy and adipose angiogenesis in WT and HO-1+/− chimeras. Chimeric mice with transplanted WT or HO-1+/− bone marrow were fed a regular chow (RC) diet or a HFD for 36 weeks. The animals were sacrificed and the visceral fat tissues were sectioned and stained with hematoxylin and eosin. A, The adipocyte size was analy...

Hematopoietic HO-1 haploinsufficiency impairs monocyte migration response to MCP-1. A, The circulating monocytes were isolated from WT and HO-1+/− mice and subjected to APC-conjugated anti-CD11b and PE-conjugated anti-Ly-6G antibody staining, followed by flow cytometry. Monocytes were identified as CD11b+Ly-6G− cells. B, WT and HO-1+/− monocytes (5...

Flow cytometric analysis of circulating monocytes from WT and HO-1+/− chimeras. C57BL/6J mice were lethally irradiated and received transplantation of bone marrow cells isolated from WT and HO-1+/− mice. At 4 weeks after BMT, peripheral blood was collected and the percentages of CD11b+Ly-6G−Ly-6Chigh and CD11b+Ly-6G−Ly-6Clow monocytes were analyzed...

Genotype analysis of blood cells isolated from WT and HO-1+/− chimeras. C57BL/6J mice were lethally irradiated, followed by BMT with hematopoietic stem cells isolated from WT and HO-1+/− mice. At 24 weeks after BMT, genomic DNA was isolated from the peripheral blood and analyzed by PCR for WT allele (456 bp) and mutant allele (400 bp). (TIF)

Effect of hematopoietic HO-1 haploinsufficiency on HO activity and intracellular ROS level in macrophages. Peritoneal macrophages were isolated from WT and HO-1+/− mice receiving thioglycollate injection for 4 days. A, HO activity in whole cell lysates was determined and expressed as nmoles of bilirubin produced per mg proteins per h. The number of...

The TRC8 gene, which was previously shown to be disrupted by a 3;8 chromosomal translocation in hereditary kidney cancer, encodes for an endoplasmic reticulum-resident E3 ligase. Studies have shown that TRC8 exhibits a tumor-suppressive effect through its E3-ligase activity. Therefore, the identification of its physiological substrates will provide...

Heme oxygenase-1 (HO-1) is a stress-inducible enzyme catalyzing the oxidative degradation of heme to free iron, CO, and biliverdin. Previous studies demonstrated that HO-1 overexpression promoted VEGF expression and angiogenesis in the ischemic heart. However, the underlying mechanism remained elusive. Here we show that adenovirus-mediated HO-1 tra...

Haem oxygenase 1 (HO-1) has strong anti-apoptotic, anti-inflammatory and antioxidative effects that help protect cells against various forms of immune attack. We investigated whether transgenic expression of Ho-1 (also known as Hmox1) in pancreatic beta cells would protect NOD mice from autoimmune damage and prolong graft survival following islet t...

The microsatellite polymorphism of heme oxygenase (HO)-1 gene promoter has been shown to be associated with the susceptibility to ischemic event, including coronary artery disease (CAD), myocardial infarction, and peripheral vascular disease. We aimed to examine whether the length of (GT)(n) repeats in HO-1 gene promoter is associated with ischemic...

Heme oxygenase (HO) catalyzes the rate-limiting step in the oxidative degradation of cellular heme that liberates iron, carbon monoxide (CO), and biliverdin. Two distinct HO isoforms have been identified in mammalian system. Compared to HO-2, which is constitutively expressed, HO-1 is a stressresponsive protein that is highly induced by many agents...

Oxidative stresses are believed to play an important role in the induction of both cell adhesion molecules and pro-inflammatory cytokines, a key event in a variety of inflammatory processes. The enzyme heme oxygenase-1 (HO-1) functions as an antioxidant and serves to protect against tissue injury. In this study, we report that HO-1 was induced in c...

Heme oxygenase-1 (HO-1), a stress-inducible enzyme anchored in the endoplasmic reticulum (ER) by a single transmembrane segment (TMS) located at the C terminus, interacts with NADPH cytochrome P450 reductase and biliverdin reductase to catalyze heme degradation to biliverdin and its metabolite, bilirubin. Previous studies suggested that HO-1 functi...

Heme oxygenase-1 (HO-1), a stress-inducible enzyme anchored in the endoplasmic reticulum (ER) by a single transmembrane segment (TMS) located at the C terminus, interacts with NADPH cytochrome P450 reductase and biliverdin reductase to catalyze heme degradation to biliverdin and its metabolite, bilirubin. Previous studies suggested that HO-1 functi...

Increased neovascularization is commonly observed in hemorrhagic plaques and associated with rupture of atherosclerotic lesions. This study aims to investigate whether hemin accumulated at the site of hematoma promotes neovascularization through affecting the growth and function of endothelial progenitor cells (EPCs) and the possible mechanism invo...

Heme oxygenase-1 (HO-1), a heme degradation enzyme with multiple vasoprotective functions, is systemically induced in pathophysiological states associated with oxidative stress. To evaluate the impact of systemic HO-1 expression on circulating endothelial progenitor cells (EPCs) and re-endothelialization after vascular injury in an animal model. Mi...

Heme oxygenase‐1 (HO‐1) catalyzes the oxidative degradation of heme to biliverdin. Previous studies suggest that HO‐1 exists as a monomer in ER. In the present study, we performed chemical cross‐linking and fluorescence resonance energy transfer (FRET) experiments to show that HO‐1 forms dimers in ER. However, the dimerization was not observed with...

The present study investigated the cellular mechanism underlying the degradation of heme oxygenase-1 (HO-1), an endoplasmic reticulum (ER)-anchored protein. The turnover of HO-1 induced in vascular smooth muscle cells (VSMCs) was significantly attenuated by proteasome inhibitors, suggesting the involvement of a proteasome-mediated pathway. High mol...

Heme oxygenase-1 (HO-1) is a stress-inducible enzyme with multiple protective functions in cardiovascular systems. Studies have shown that the timely cardiac HO-1 overexpression at acute phase of ischemic infarction (MI) provides protection via its anti-apoptotic and anti-inflammatory effects. Here we demonstrate that a delayed HO-1 transduction me...

Heme oxygenase (HO) leads to the generation of free iron, carbon monoxide, and bilirubin. A length polymorphism of GT repeats in the promoter of human HO-1 gene has been shown to modulate gene transcription. The aim of this study was to assess the association of the length of (GT)(n) repeats in the HO-1 gene promoter with serum bilirubin, markers o...

Heme oxygenase-1 (HO-1) is an enzyme with potent immunoregulatory capacity. To evaluate the effect of HO-1 on autoimmune diabetes, female NOD mice at 9 weeks of age received a single intravenous injection of a recombinant adeno-associated virus bearing HO-1 gene (AAV-HO-1; 0.5 x 10(10)-2.5 x 10(10) viruses/mouse). In a dose-dependent manner, HO-1 t...

Allergic asthma strongly correlates with airway inflammation caused by cytokines secreted by allergen-specific type-2 T helper (Th2) cells, but the immunologic regulation of cell function is yet to be acquired. Further, IL-10 has been found to exert both antiinflammatory and immunoregulatory activities. This study aimed to elucidate the therapeutic...

Arterial thrombosis is a critical event in the pathogenesis of lesion development. In this study, we evaluated the effect of heme oxygenase-1 (HO-1), a stress-inducible enzyme with vasoprotective functions, on arterial thrombosis following vascular mechanical injury. The carotid arteries of apoE-deficient mice were subjected to angioplasty with a m...

The aim of this study was to investigate the efficiency of adenoviral-mediated transfer of the interleukin (IL)-10 gene for inhibition of experimental autoimmune anterior uveitis, a rat model of human acute anterior uveitis. Uveitis was induced in the Lewis rat by simultaneous injection of melanin-associated antigen intraperitoneally (i.p.) and int...

Heme oxygenase-1 (HO-1) is induced in the CNS after hemorrhage, and may have an effect on injury to surrounding tissue. Hemin, the preferred substrate of HO, is a neurotoxin that is present in intracranial hematomas. In a prior study, we observed that HO inhibitors increased the vulnerability of cultured cortical astrocytes to heme-mediated oxidati...

Heme oxygenase-1 (HO-1) has been implicated in antioxidant and anti-inflammatory actions. To characterize the role of HO-1 in the vascular inflammatory response, we examined the effect of HO-1 on the expression of inducible nitric oxide synthase (iNOS) induced by interleukin-1beta (IL-1beta) in rat vascular smooth muscle cells (VSMCs). Western blot...

Heme oxygenase-1 (HO-1) is a stress-response enzyme implicated in cardioprotection. To explore whether HO-1 has a role in cardiac remodeling response, the effect of its overexpression on angiotensin II (Ang II)-induced cardiac hypertrophy was examined. HO-1 was induced in cultured rat neonatal cardiomyocytes by treatment with cobalt protoporphyrin...

Heme oxygenase-1 (HO-1) is a rate-limiting enzyme in heme degradation, leading to the generation of free iron, biliverdin, and carbon monoxide (CO). CO exerts potent antiproliferative and anti-inflammatory effects in the vascular walls, thereby influencing neointimal formation after vascular injury. A dinucleotide GT repeat in the promotor region o...

Accumulative evidence has supported the role of iron in the development of atherosclerosis. To test whether iron-mediated oxidative stress influences plaque stability, apoliporotein-E (ApoE)-deficient mice (3 months old) were placed on a chow diet or a low-iron diet for 3 months, and the abundance of interstitial collagen and the expression of the...

15-Deoxy-Delta 12,14-prostaglandin J2 (15d-PGJ2), a cyclopentenone prostaglandin, displays a potent anti-inflammatory effect at micromolar concentrations (>2 microM) through direct inhibition of nuclear factor (NF)-kappa B activation. Here we show that at submicromolar concentrations (0.1-0.5 microM) 15d-PGJ2 retains the ability to suppress the pro...

Heme oxygenase is a rate-limiting enzyme in heme degradation, leading to the generation of free iron, biliverdin, and carbon monoxide. Induction of heme oxygenase-1 is implicated in the antioxidant defense mechanism and can modulate vascular function. To test the association of microsatellite polymorphism in the promoter region of human HO-1 gene w...

The mechanisms underlying the action of the potent anti-inflammatory interleukin-10 (IL-10) are poorly understood. Here we show that, in murine macrophages, IL-10 induces expression of heme oxygenase-1 (HO-1), a stress-inducible protein with potential anti-inflammatory effect, via a p38 mitogen-activated protein kinase-dependent pathway. Inhibition...

Heme oxygenase (HO) is the rate-limiting enzyme to catalyze the heme degradation, leading to the generation of biliverdin, which is subsequently converted to antioxidant bilirubin by biliverdin reductase,1,2 free iron, and carbon monoxide (CO). Three HO isozymes derived from distinct genes were identified.3 Among them, HO-1 is a stress-responsive p...

Increasing evidence supports the role of heme oxygenase-1 (HO-1) in cytoprotective response and iron homeostasis. The object of this study was to investigate whether adenovirus-mediated gene transfer of HO-1 in arteries reduces iron overload and inhibits lesion formation in apolipoprotein E (apoE)-deficient mice. Infection of rat aortic smooth musc...

Oxidized low-density lipoprotein (oxLDL) is a potent inducer of apoptosis for vascular cells. In the present study, we demonstrate that the expression of death mediators, including p53, Fas, and Fas ligand (FasL) was substantially upregulated by oxLDL in cultured vascular smooth muscle cells (SMCs). The induction of these death mediators was time d...

Iron is a vital element in life. However, it may participate in diverse pathological processes by catalyzing the formation of reactive oxygen free radicals. During the past decade, considerable evidence has supported the role of oxidative stress in the development of atherosclerosis and related cardiovascular diseases. The oxidation of low-density...

Iron may catalyse the production of reactive oxygen species during post-ischemic reoxygenation and subsequently lead to brain damage. Ferritin, an iron sequestering and storage protein, can also be a source of iron after ischemic insult. However, its role in ischemia-reperfusion has not been carefully investigated. In the present study, we examined...

We have previously demonstrated that phorbol myristate acetate (PMA) up-regulates H-ferritin gene expression in myeloid cells by stabilization of its message. In the present report, we showed that insertion of the 3′-untranslated region (3′-UTR) of H-ferritin mRNA at the 3′-end of luciferase coding sequence significantly reduced the stability of lu...

The death of macrophage-derived foam cells contributes to the formation of the lipid core in atherosclerotic lesions. Although the underlying mechanism is not yet clear, apoptosis has been shown to be responsible, at least in part, for the cell death of lipid-laden macrophages in atherosclerotic plaques. In the present study, we demonstrated that c...

Iron deposition has been shown to be prominent in atherosclerotic lesions. However, the source of iron accumulated in arterial walls is unclear. In present report, we provide the histological evidence to demonstrate the localization of erythrocytes in atherosclerotic lesions from experimental animals. As revealed by scanning and transmission electr...

The cytokine profile of atherosclerotic aortas from apoE-deficient mice was assessed by reverse transcriptase-polymerase chain reaction. The results clearly showed that the expression of mRNA for IL-12p40 was evident in aortas from 3-month-old apoE-deficient mice. The mRNA for IL-10 was detected in aorta from these mice at the age of 6 months, indi...

Iron deposition is evident in human atherosclerotic lesions, suggesting that iron may play a role in the development of atherosclerosis. To test this idea, the correlation between the extent of iron deposition and the severity of atherosclerosis in apolipoprotein E (apoE)-deficient mice was investigated. Furthermore, the effect of a low-iron diet o...

The presence of ceroid, a complex of protein associated with oxidized lipids, is commonly observed in human atherosclerotic lesions. When the human aortic walls were examined by Perls' staining, it was found that the iron deposits were evident in aortas with atherosclerosis. The extent of iron deposition was associated with the severity of the lesi...

Heme oxygenase-1 (HO-1) is a heme-degradation enzyme induced under various oxidative stress conditions. To elucidate the potential involvement of HO-1 in atherogenesis, the expression of this enzyme in atherosclerotic lesions of apolipoprotein E-deficient mice and humans were examined. Both immunostaining and in situ hybridization clearly demonstra...

Human aortic aneurysm is commonly characterized by the presence of advanced atherosclerosis associated with variable chronic adventitial inflammation. Histological examination of human aortic aneurysmal specimens revealed the presence of plasma cells and lymphoid aggregates in media and adventitia of the vessels. Immunostaining further demonstrated...

The expression of platelet-activating factor (PAF) receptor gene was up-regulated in a time- and dose-dependent manner in a B cell line (Ramos) following exposure to TGF-beta 2. The TGF-beta 2-induced increment of PAF receptor mRNA was at least partly due to an increase in transcriptional rate as demonstrated by nuclear run-off experiments. Transie...

The mRNA coding for H-ferritin was highly induced in human monocytic THP-1 cells following treatment with phorbol 12-myristate 13-acetate (PMA). The induction was detected at 3 h, reached maximal levels at 12 h, and was sustained for up to 48 h subsequent to PMA exposure. PMA-induced up-regulation of H-ferritin gene expression was also observed in...

H-ferritin gene expression was highly induced in human monocytic THP-1 cells following TPA-induced differentiation toward macrophages. The induction was detected at 3 hr, reached maximal level at 12 hr and sustained up to 48 hr after exposure to TPA. The TPA-induced up-regulation of H-ferritin gene expression was also observed in other leukemic cel...

To identify genes potentially implicated in atherogenesis, a cDNA library was constructed from human atherosclerotic aorta and differentially screened with 32P-labeled-cDNAs prepared from human normal and atherosclerotic aortas. Two cDNA clones exhibiting higher hybridization to the 32P-labeled cDNAs from atherosclerotic vessels were isolated and i...

Platelet-activating factor (PAF) is a potent inflammatory mediator implicated in a variety of pathophysiological states1–2. PAF exerts a wide spectrum of biological activities via binding to specific receptors present on the surface of many types of cells, including platelets, neutrophils, monocytes, eosinophils, lymphocytes, vascular endothelial c...

To understand the molecular mechanisms that direct the expression of the gene encoding the platelet-activating factor (PAF) receptor, the 5'-flanking region of the human PAF receptor gene was cloned, and its promoter activity in myeloid cell lines was characterized. By the 5'-rapid amplification of cDNA ends method and primer extension, the transcr...

Prolonged exposure (8-24 h) of human promonocytic U937 cells to 100 nM 1-O-hexadecyl-2-N-methylcarbamyl-sn-glycero-3-phosphocholine (carbarmyl-PAF), a non-metabolizable analogue of platelet-activating factor (PAF), reduced the numbers of PAF receptors by 50-75%, as determined by the radioligand-binding assay. To clarify whether the down-regulation...

Addition of endothelins (ETs) to neuroblastoma-glioma hybrid cells (NG108-15) induced increases in cytosolic free Ca2+ ([Ca2+]i) levels of labeled inositol monophosphates and inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. The increases in [Ca2+]i elicited by the three ETs (ET-1, ET-2, and ET-3) were transient and did not show a sustained phase. Chela...

Platelet-activating factor (PAF) elicited an increase in intracellular Ca2+ concentration, [Ca2+]i, in neuroblastoma x glioma hybrid NG 108-15 cells as measured by fura-2 fluorescence method. The rise in [Ca2+]i was primarily due to the influx of Ca2+ from extracellular source. Preincubation of cells with the Ca(2+)-ion channel blockers, including...

Platelet-activating factor (PAF) initiated polyphosphoinositide (polyPI) breakdown and a rise of intracellular calcium concentration ([Ca2+]i) in neuroblastoma x glioma hybrid NG 108-15 cells. The accumulation of [3H]inositol trisphosphate and [3H]inositol bisphosphate was evident within 15 s after PAF stimulation, peaked at 1 min, and then gradual...

Rabbit platelets pretreated with platelet activating factor (PAF) became refractory to further stimulation by PAF. The effect was specific for PAF. In this study, the alteration in the specific agonist binding to PAF receptor in platelets following desensitization was investigated. As revealed by the Scatchard analysis of radioligand binding data,...

A monoclonal antibody (MAb) raised against rabbit platelet membranes was shown to be a strong agonist to induce platelet aggregation and secretion. This MAb, designated 19CB-1, was identified as an IgM and purified to near homogeneity by ammonium sulfate precipitation and Q-sepharose column chromatography. Aggregation induced by 19CB-1 was only sli...

Leukotriene C4 (LTC4), one of the major constituents of the slow reacting substance of anaphylaxis, induced a dose-dependent hydrolysis of phosphoinositides in [3H]inositol-prelabeled rat basophilic leukemia (RBL-1) cells. The EC50 for LTC4 to elicit the half maximum accumulation of [3H]inositol phosphates (IPs) was around 20 nM. The increase in th...

A photoreactive, radioiodinated derivative of platelet activating factor (PAF), 1-O-(4-azido-2-hydroxy-3-iodobenzamido)undecyl-2-O-acetyl-sn- glycero-3-phosphocholine ([125I]AAGP), was synthesized and used as a photoaffinity probe to study the PAF binding sites in rabbit platelet membranes. The nonradioactive analog, IAAGP, induced rabbit platelet...

In the present study, we have characterized the properties of both diglyceride lipase (lipoprotein lipase, EC 3.1.1.24) and monoglyceride lipases (acylglycerol lipase, EC 3.1.1.23) in an attempt to assess the potential roles of these two enzymes in the release of arachidonate in activated human platelets. Diglyceride lipase exhibited maximal activi...

AbstractA synthesis of phosphocholine 9 was accomplished in 36% yield from isopropylidene glycerol in contrast to 2% yield as reported previously. Since 9 has been converted to platelet activating factor‐analogue 2, this report constitutes a more practical synthesis of 2.

Rabbit platelet membranes, preincubated with 3H-labeled platelet activating factor ([3H]PAF), were solubilized with 2% digitonin. Sedimentation of the detergent extract in a sucrose density gradient revealed a major labeled component with a sedimentation coefficient (s20,omega) of 10.5 S, which was substantially diminished when an excess of unlabel...

Studies of the molecular structures and biological activities of leukotrienes (LTs) provided evidence for the presence of multiple, subclass-specific receptors on the surface of responding tissues. Distinct receptors for LTC4 and LTD4 have been defined based on functional and metabolic criteria. However, radioligand-binding studies of LTC4-binding...

The subcellular distribution of specific binding sites for [3H]leukotriene C4 ([3H]LTC4) was analyzed after sedimentation of organelles from disrupted bovine aortic endothelial cells on sucrose density gradients and was shown to be in membrane fractions I (20% sucrose) and IV (35% sucrose). Saturation binding studies of [3H]LTC4 on endothelial cell...

A soluble high affinity binding unit for leukotriene (LT) C4 in the high speed supernatant of rat liver homogenate was characterized at 4 degrees C as having a single type of saturable affinity site with a dissociation constant of 0.77 +/- 0.27 nM (mean +/- S.E., n = 5). The binding activity was identified as the liver cytosolic subunit 1 (Ya) of g...

Human platelets prelabeled with arachidonate exhibited a rapid and transient rise in arachidonoyl monoglyceride in addition to arachidonoyl diglyceride following thrombin stimulation. Substantial release of arachidonate and its metabolites also occurred at the early phase. Preincubation of labeled platelets with RHC 80267, a potent inhibitor of dig...

Two forms of phosphatidylinositol-specific phospholipase C from human platelet cytosol were resolved by DEAE-cellulose chromatography and purified further by hydrophobic chromatography. Both forms utilized phosphatidylinositol as the best substrate. However, the enzyme did not distinguish 2-arachidonylphosphatidylinositol from 2-oleoylphosphatidyli...

Two forms of phosphatidylinositol-specific phospholipase C from human platelet cytosol were resolved by DEAE-cellulose chromatography and purified further by hydrophobic chromatography. Both forms utilized phosphatidylinositol as the best substrate. However, the enzyme did not distinguish 2-arachidonylphosphatidylinositol from 2-oleoylphosphatidyli...

Release of arachidonate from 2-arachidonyl diglyceride by human platelet microsomes was investigated. Diglycerides labeled with 14C-stearate at sn-1 and with 3H-arachidonate at sn-2 were used as a substrate for microsomal diglyceride lipase. Diglyceride was deacylated first at sn-1 as evidenced by the accumulation of 2-arachidonyl monoglyceride but...

Iron is a vital element in life. However, it may participate in diverse pathological processes by catalyzing the formation of reactive oxygen free radicals. During the past decade, considerable evidence has supported the role of oxidative stress in the development of atherosclerosis and related cardiovascular diseases. The oxidation of low-density...