Human atrial natriuretic peptide gene delivery reduces blood pressure in hypertensive rats.
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Animals↗
Biomedical subjects
K F Lin
Publications and source records attributed to K F Lin.
Magnolol, a potent antioxidant from Magnolia officinalis, attenuates intimal thickening and MCP-1 expression after balloon injury of the aorta in cholesterol-fed rabbits.
BACKGROUND: Restenosis is a common complication after balloon angioplasty. A number of cytokines, chemotactic factors and growth factors may be involved. Several antioxidants have been shown to inhibit intimal thickening after balloon injury in hyperlipidemic animals. OBJECTIVES: The effects of magnolol on the expression of monocyte chemotactic protein-1 (MCP-1) and intimal response in balloon injured aorta of cholesterol-fed rabbits were investigated. METHODS: Male New Zealand white rabbits were fed a 2% high cholesterol (HC) diet together with daily intramuscular injection of either 1 microg/kg B.W. of magnolol (HC-M, n = 10) or vehicle (propylene glycol) as a control (HC-C, n = 10) for a total of 6 weeks. Another 10 rabbits fed a regular diet also served as a control (C) group. A balloon denudation of abdominal aorta was performed in each group at the end of the third week. The aortas were harvested at the end of 6 weeks. RESULTS: Magnolol treatment significantly inhibited Cu2+-induced LDL oxidation in cholesterol-fed rabbits and reduced atheroma formation [atheroma area ratio: 0.10 +/- 0.03 (HC-M) versus 0.33 +/- 0.07 (HC-C), p < 0.05] in thoracic aortas without lowering serum cholesterol. The intimal response was significantly attenuated in the HC-M rabbits when compared to those of the HC-C group [intimal thickness: 88.95 +/- 14.91 microm (HC-M) versus 198.02 +/- 20.35 microm (HC-C), p < 0.05; intimal area: 278.21 +/- 43.16 x 10(3) microm2 (HC-M) versus 642.70 +/- 65.01 x 10(3) microm2 (HC-C), p < 0.05]. The MCP-1 mRNA and protein expression were reduced in the HC-M group compared to the HC-C and C groups. CONCLUSION: The inhibitory effects on intimal hyperplasia and MCP-1 expression might be attributed to the antioxidant capacity of magnolol instead of lowering serum cholesterol. Magnolol may offer some protection against postangioplasty restenosis.
Angioplasty, Balloon↗
Intravenous insecticide injection-induced acute respiratory distress syndrome successfully treated with steroid therapy.
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Adult↗
Improvement of phase I drug metabolism with Schisandra chinensis against CCl4 hepatotoxicity in a rat model.
The seed extract of Schisandra chinensis was investigated in the rat for its restorative or therapeutic effect on Phase I hepatic drug metabolism following intoxication by carbon tetrachloride (CCl4). Male Sprague Dawley rats (220-250 g) were divided into two sets, one included rats with or without CCl4 intoxication, the other included CCl4 intoxicated rats with or without treatment of Schisandra extract. With the treatment regimen, rats received four oral doses of Schisandra (160 mg/kg) or the same volume of water at 8, 24, 32 and 48 h after CCl4 intoxication. A single oral dose (80 mg/kg) of antipyrine, a conventional probe for oxidative drug metabolism, was then administered. The levels of liver serum transaminases and cytochrome P450 were measured and the pharmacokinetics of antipyrine were assessed using a non-compartmental approach via WinNonlin. In comparison to the rats without CCl4 intoxication (t1/2: 2.2 +/- 0.9 h; Cl/F: 0.30 +/- 0.01 L/h/Kg; P450: 0.611 +/- 0.190 nmol/mg protein), CCl4 administration significantly decreased elimination (t1/2: 12.0 +/- 3.9 h) and oral clearance (Cl/F: 0.049 +/- 0.018 L/h/kg) of antipyrine, and markedly reduced the content of P450 (0.075 +/- 0.011 nmol/mg protein). Data obtained from intoxicated animals treated by Schisandra extract, compared to those without treatment, showed significant (p < 0.05) improvement in the t1/2 (4.45 +/- 1.7 h) and Cl/F (0.096 +/- 0.018 ml/h) estimates of antipyrine and a 2-3 fold increase in P450 level (0.190 +/- 0.072 nmol/mg protein). Findings in this study suggest that the seed extract of Schisandra appeared to be a promising agent for the improvement of Phase I oxidative metabolism in the liver damaged by CCl4.
Animals↗
Adenovirus-mediated human tissue kallikrein gene delivery inhibits neointima formation induced by interruption of blood flow in mice.
Tissue kallikrein cleaves kininogen to produce vasoactive kinin peptides. Binding of kinins to bradykinin B(2) receptors on vascular endothelial cells stimulates the release of nitric oxide and prostacyclin, thus activating the cGMP and cAMP pathways. In this study, we evaluated the effects of adenovirus-mediated human tissue kallikrein gene (Ad.CMV-cHK) delivery in a mouse model of arterial remodeling induced by permanent alteration in shear stress conditions. Mice underwent ligature of the left common carotid artery and were injected intravenously with saline or 1.8 x 10(9) plaque-forming units of Ad.CMV-cHK or control virus (Ad.CMV-LacZ). Fourteen days after surgery, morphometric analysis revealed that Ad. CMV-cHK reduced neointima formation by 52% (P<0.05) compared with Ad. CMV-LacZ. Expression of human tissue kallikrein (HK) mRNA was detected in mouse carotid artery, aorta, kidney, heart, and liver, and recombinant HK was present in the urine and plasma of mice receiving HK gene. Kallikrein gene transfer resulted in increases in urinary kinin, cGMP, and cAMP levels. The protective action of Ad. CMV-cHK on neointima formation was significantly reduced (P<0.05) in mice with knockout of the kinin B(2) receptor gene compared with wild-type control mice (J129Sv mice). In contrast, the effect of Ad. CMV-cHK was amplified (P<0.05) in transgenic mice overexpressing human B(2) receptor compared with wild-type control mice (c57/Bl6 mice). Thus, the inhibitory effect of recombinant kallikrein on structural alterations caused by the interruption of blood flow appears to be mediated by the B(2) receptor. These results provide new insight into the role of the tissue kallikrein-kinin system in vascular remodeling and suggest the application of HK gene therapy to treat restenosis and atherosclerosis.
Adenoviridae↗
Evaluation of the protective effects of Schisandra chinensis on Phase I drug metabolism using a CCl4 intoxication model.
To evaluate the potential activity of Schisandra chinensis in restoring hepatic drug metabolism in CCl4 damaged liver, antipyrine was employed as a probe for the possible effects of the herb on Phase I oxidative metabolism in rats. Schisandra lignan fraction (160 mg/kg) was given orally to male Sprague-Dawley rats (220-240 g) 30 min or 6 h before CCl4 intoxication (4 ml/kg, s.c.). Following a single oral dose of antipyrine (80 mg/kg) to the rats with damaged liver, the pharmacokinetics of antipyrine in whole blood were determined and levels of liver enzymes, e.g. SGPT, SGOT, and cytochrome P450 were measured. Pharmacokinetic parameters for antipyrine were estimated using noncompartmental analysis. Results indicated that CCl4 significantly increased the elimination half-life (t(1/2)) of antipyrine from 2.59 +/- 1.04 to 11.25 +/- 3.91 h (P < 0.001) and decreased its clearance (CL) from 65.94 to 10.84 ml/h as compared to control. Pretreatment with the Schisandra lignan fraction 30 min or 6 h before intoxication significantly (P < 0.001) improved antipyrine elimination by reducing its t(1/2) to 3.30 +/- 0.52 and 3.58 +/- 1.05 h, respectively. The corresponding improvements observed for CL, i.e. 49.06 +/- 21.75 ml/h (P < 0.01); 21.10 +/- 10.42 ml/h (P < 0.05), were also substantial. Moreover, normalization of SGPT, SGOT and P450 levels was observed with the two Schisandra pretreatment schedules. In conclusion, Schisandra lignans exhibited strong protective effect on Phase I oxidative metabolism in the liver damaged by CCl4. Furthermore, pretreatment of Schisandra 30 min before intoxication showed a more pronounced effect than that of the 6 h pretreatment. The current pharmacokinetic approach allowed the protective effects of Schisandra on oxidative drug metabolism in damaged liver to be systemically examined and will certainly help in the evaluation of hepato-protectants obtained from natural sources.
Animals↗
Atrial natriuretic peptide gene delivery reduces stroke-induced mortality rate in Dahl salt-sensitive rats.
Atrial natriuretic peptide (ANP) is a powerful hormone with hypotensive, natriuretic, diuretic, and many other beneficial effects. Direct infusion of ANP in therapeutics has limited success because of its short half-life in the circulation. Our previous studies have shown that ANP gene delivery attenuates hypertension, cardiac hypertrophy, and renal injury in Dahl salt-sensitive (Dahl-SS) rats. To investigate the potential therapeutic value of ANP gene delivery on salt-induced stroke and cerebrovascular disorders, an adenovirus harboring the human ANP gene (Ad.RSV-cANP) was injected into Dahl-SS rats on a high salt diet. A single intravenous injection of the ANP gene caused a significant reduction of blood pressure that lasted for more than 3 weeks. A maximal blood pressure reduction of 28 mm Hg was observed 2 weeks after gene delivery as compared with that of control rats injected with adenovirus harboring the LacZ gene under the control of the Rous sarcoma virus promoter (Ad.RSV-LacZ). Immunoreactive human ANP can be detected in the heart, lung, kidney, and brain of rats after gene delivery. The stroke mortality rate of Dahl-SS rats was significantly decreased (from 54% to 17% at 3 weeks and from 70% to 50% at 4 weeks after ANP gene delivery as compared with rats injected with control virus). ANP gene delivery also significantly attenuates salt-induced aortic hypertrophy as evidenced by reduced thickness of the aortic wall. This is the first study to demonstrate the potential of ANP gene delivery in reducing the mortality rate caused by cerebrovascular disorders and stroke. Successful application of this technology may have potential value in treating individuals with a high risk of stroke.
Adenoviridae↗
Human tissue kallikrein attenuates hypertension and secretes into circulation and urine after intramuscular gene delivery in hypertensive rats.
Systemic delivery of the human tissue kallikrein transgene has been shown to markedly delay the increase of blood pressure in hypertensive rat models. To demonstrate potential hypotensive effects of kallikrein via local delivery, adenovirus carrying the human tissue kallikrein gene was inoculated into quadriceps of spontaneously hypertensive rats (SHR). A single intramuscular injection of the kallikrein gene caused a significant delay of blood pressure increase for 5 weeks. The expression of human tissue kallikrein and its mRNA was identified solely in injected muscle. Immunoreactive human tissue kallikrein was detected in the muscle as well as in the circulation and urine of adult and newborn rats. Urinary kinin and cGMP levels increased significantly in rats receiving kallikrein gene delivery as compared with rats receiving control virus containing the LacZ gene. The detection of human tissue kallikrein in rat urine after local gene delivery into the muscle provides direct evidence that circulatory kallikrein can be secreted into the urine. These findings indicated that a continuous supply of human tissue kallikrein in the circulation is sufficient to reduce blood pressure and kallikrein gene delivery via the intramuscular route may have significant implications in therapeutic applications.
Adenoviridae↗
Atrial natriuretic peptide gene delivery attenuates hypertension, cardiac hypertrophy, and renal injury in salt-sensitive rats.
To investigate potential therapeutic effects of atrial natriuretic peptide (ANP) gene delivery on renal and cardiac disorders, adenovirus harboring the human ANP gene (Ad.RSV-cANP) was delivered into Dahl salt-sensitive (DSS) rats on a high-salt diet. A single intravenous injection of the ANP gene caused a significant delay of blood pressure increase 3 days post-injection and the effect lasted for more than 5 weeks. A maximal blood pressure reduction of 32.8 mmHg was observed after ANP gene delivery, as compared with that of control rats injected with Ad.CMV-LacZ. Immunoreactive human ANP can be detected in the heart, lung, and kidney of rats after gene delivery. ANP gene delivery caused significant increases in renal blood flow, glomerular filtration rate, sodium output, urine excretion, and urinary cGMP levels. These beneficial effects were reflected morphologically by a reduction in cardiomyocyte size, attenuation of the glomerular-sclerotic lesions, tubular injury and arterial thickening. This study demonstrated the usefulness of somatic gene transfer as a new tool for ANP gene delivery in studying salt-related hypertension and renal and cardiovascular diseases. In addition, the findings also suggest that ANP gene delivery may have potential in therapeutic applications.
Adenoviridae↗
Human kallikrein gene delivery attenuates hypertension, cardiac hypertrophy, and renal injury in Dahl salt-sensitive rats.
The tissue kallikrein-kinin system has been documented to be involved in the pathogenesis of hypertension and renal diseases. To investigate the protective effects of kallikrein gene delivery on salt-induced renal damage, cardiac dysfunction, and hypertension, adenovirus harboring the human tissue kallikrein gene under the control of the cytomegalovirus promoter Ad.CMV-cHK was delivered into Dahl salt-sensitive (Dahl-SS) rats fed to a high-salt (4% NaCl) diet. A single intravenous injection of Ad.CMV-cHK resulted in a significant reduction of blood pressure beginning 2 days post injection and the effect lasted for 4 weeks. The human kallikrein mRNA was detected in rat heart, kidney, lung, liver, and adrenal gland; immunoreactive human kallikrein can be measured in the liver, kidney, sera, and urine of rats receiving kallikrein gene delivery. Following Ad.CMV-cHK injection, a significant increase in urine excretion, urinary sodium output, kinin, and cGMP level was observed. Kallikrein gene delivery caused a significant reduction in the left ventricular mass and cardiomyocyte size as well as inhibition of glomerular sclerotic lesions and tubular dilatation. This study shows that adenovirus-mediated gene delivery in Dahl-SS rats fed a high-salt diet resulted in (i) prolonged reduction of blood pressure and increased urinary kinin and cGMP levels, consistent with blood pressure reductions mediated via kinin through a cGMP-dependent signal transduction pathway, (ii) inhibition of cardiac hypertrophy, and (iii) attenuation of renal injury. The ability of kallikrein gene transfer to produce a wide spectrum of beneficial effects makes it an excellent candidate in treating salt-related hypertension as well as cardiovascular and renal diseases.
Adenoviridae↗
Adenovirus-mediated kallikrein gene delivery reverses salt-induced renal injury in Dahl salt-sensitive rats.
BACKGROUND: The tissue kallikrein-kinin system has been shown to play a role in cardiac and renal functions. In this study, we investigated the ability of kallikrein gene delivery to reverse salt-induced cardiac hypertrophy and renal injury in Dahl salt-sensitive rats. METHODS: Adenovirus harboring the human tissue kallikrein gene, Ad.CMV-cHK, was delivered intravenously into Dahl salt-sensitive rats suffering from hypertension, cardiac hypertrophy and renal damage induced by a high salt diet (4% NaCl) for four weeks. RESULTS: Expression of human kallikrein mRNA was detected in rat kidney, heart, aorta and liver, and immunoreactive human kallikrein levels were measured in the serum and urine of rats receiving gene delivery. A single injection of Ad.CMV-cHK caused a significant reduction of blood pressure for more than two weeks. Kallikrein gene transfer caused left ventricular mass reduction and elevated glomerular filtration rate, renal blood flow, urinary excretion, urinary kinin, nitrite/nitrate content, cGMP and cAMP levels. Morphological investigations showed that kallikrein gene transfer caused a significant reversal in salt-induced tissue and organ damage. In the heart, cardiac hypertrophy and fibrosis were reduced, and in the kidney, both glomerular sclerotic lesions and tubular damage were reversed. CONCLUSIONS: Adenovirus-mediated kallikrein gene delivery is effective in reversing salt-induced cardiac hypertrophy and renal injury in Dahl-salt sensitive rats.
Adenoviridae↗
Localization and secretion of tissue kallikrein in peptidoglycan-induced enterocolitis in Lewis rats.
The plasma kallikrein-kinin system is a mediator of intestinal inflammation induced by peptidoglycan-polysaccharide from group A streptococci (PG-APS) in rats. In this study we investigated the participation of intestinal tissue kallikrein (ITK). Lewis rats were injected intramurally with PG-APS. ITK was visualized by immunohistochemical staining. Cecal ITK concentration was measured by radioimmunoassay, and gene expression was evaluated by RNase protection assay. Kallikrein-binding protein (KBP) was evaluated in plasma by ELISA. Tissue kallikrein was identified in cecal goblet cells in both control and PG-APS-injected rats and in macrophages forming granulomas in inflamed tissues. Cecal ITK was significantly lower in acute and chronic phases of inflammation and in supernatant from in vitro cultures of inflamed cecum. ITK mRNA levels were not significantly different. Plasma KBP levels were significantly reduced in inflamed rats. The presence of tissue kallikrein in macrophages suggests participation in experimental colitis. The decrease of ITK in the inflamed intestine associated with unchanged mRNA levels suggests ITK release during intestinal inflammation.
Animals↗
Prolonged reduction of high blood pressure with human nitric oxide synthase gene delivery.
Endothelium-derived nitric oxide (NO) in peripheral vessels has been shown to modulate vascular resistance and blood pressure. We explored the effect of a continuous supply of human endothelial NO synthase (eNOS) on the blood pressure of spontaneously hypertensive rats (SHR) by somatic gene delivery. A DNA construct containing the human eNOS gene fused to the cytomegalovirus promoter/enhancer was injected into SHR through the tail vein. A single injection of the naked eNOS plasmid DNA caused a significant reduction of systemic blood pressure for 5 to 6 weeks in SHR, and the effect continued for up to 10 to 12 weeks after a second injection. The differences were significant from 2 to 12 weeks postinjections (n=6, P<.01). In a separate experiment, L-arginine, the substrate of eNOS, was supplied in drinking water at a concentration of 7.5 g/L for 11 weeks after eNOS gene delivery. A maximal blood pressure reduction of 21 mm Hg in SHR was observed with eNOS DNA compared with that of control SHR injected with vector DNA (181.9+/-1.46 versus 202.7+/-2.79 mm Hg, mean+/-SEM, n=6, P<.01). Human eNOS gene delivery induces significant increases in urinary and aortic cGMP levels and urinary and serum nitrite/nitrate content (P<.05), while no significant differences in body weight, heart rate, water intake, food consumption, or urine excretion were observed. These results indicate that somatic delivery of the human eNOS gene induces a prolonged reduction of high blood pressure and raises the potential of using eNOS gene therapy for hypertension and cardiovascular diseases.
Animals↗
Adrenomedullin gene delivery reduces blood pressure in spontaneously hypertensive rats.
Adrenomedullin (ADM) is a potent vasoactive peptide. In this study, we explored the effects of a continuous supply of ADM by somatic gene delivery on spontaneously hypertensive rats (SHR). DNA constructs containing the human ADM cDNA fused to either the cytomegalovirus promoter (CMV-cADM) or Rous Sarcoma virus 3'-long terminal repeat (RSV-cADM) were intravenously injected into SHR through the tail vein. Expression of human ADM in SHR was identified in the kidney, adrenal gland, heart, and lung by radioimmunoassay and reverse transcription-polymerase chain reaction followed by Southern blot analysis. A single injection of ADM plasmid DNA in young adult SHR (7 wk old) caused a significant reduction in systolic blood pressure for up to 5 wk (p < 0.05). A second injection of CMV-cADM 5 wk after the first delivery resulted in a further reduction in blood pressure for another 3 wk (p < 0.001). A maximal blood pressure reduction of 22 mmHg in SHR was observed 7 wk after injection of CMV-cADM plasmid DNA (185 +/- 1.7 mmHg, n = 6, p < 0.001), and a reduction of 15 mmHg was observed after injection of RSV-cADM (192 +/- 2.7 mmHg, n = 6, p < 0.001), as compared with control rats given vector DNA (207 +/- 2.4 mmHg, n = 6). Similarly, injection of CMV-cADM plasmid DNA in adult SHR (10 wk old) resulted in a significant reduction in blood pressure for up to 6 wk. Antibodies to either human ADM or its plasmid DNA were not detected in rat sera after the second injection. These studies indicate that intravenous injection of the human ADM gene in hypertensive rats results in expression of the foreign gene and induces a long-lasting reduction in blood pressure.
Adrenomedullin↗
Kallikrein gene therapy in newborn and adult hypertensive rats.
The tissue kallikrein-kinin system has been postulated to play an important role in blood pressure regulation. Kallikreins are serine proteinases that release potent vasodilating kinin peptides from precursor kininogens by limited proteolysis. Our recent studies show that systemic delivery of the human tissue kallikrein gene into adult spontaneously hypertensive rats (SHR) results in a sustained reduction of blood pressure for several weeks. The goal of this study is to evaluate whether early delivery of the kallikrein gene into newborn SHR could exert a suppressive effect on blood pressure phenotype during rat growth and development. A human tissue kallikrein cDNA construct, under the control of cytomegalovirus promoter (CMV-cHK), or vector DNA was injected subcutaneously into the necks of 2-day-old SHR. Blood pressures were monitored biweekly from 3 to 19 weeks by the tail-cuff method. A single injection of the human kallikrein cDNA construct caused a significant reduction of blood pressure (n = 6, p < 0.001) from 11 to 17 weeks after injection compared with control rats receiving vector DNA. Intravenous delivery of the human tissue kallikrein gene into adult SHR produced blood pressure lowering effects (n = 6, p < 0.001) that lasted for 6 weeks in male but not in female rats. The expression of human tissue kallikrein in rats was identified by reverse transcription polymerase chain reaction followed by Southern blot analysis and an ELISA specific for human tissue kallikrein. Kallikrein gene delivery did not cause any changes in body weight, urine volume, or water intake in the experimental animals compared with the control group. No antibodies to either human tissue kallikrein or its DNA were detected in rat sera 19 weeks postinjection. These results show that delivery of the kallikrein gene at an early stage of life has a protective effect against development of hypertension in adult SHR and that gender differences could be a factor in kallikrein gene therapy for the treatment of hypertensive disorders.
Aging↗
Human atrial natriuretic peptide gene delivery reduces blood pressure in hypertensive rats.
Chronic infusion of atrial natriuretic peptide (ANP) has been shown to cause natriuresis, diuresis, and hypotension in rats and humans. We explored the effect of a continuous supply of ANP by somatic ANP delivery on genetically hypertensive rats. A DNA construct containing the human ANP gene fused to the Rous sarcoma virus 3'-long terminal repeat (RSV-LTR) was injected intravenously into spontaneously hypertensive rats (SHR) through the tail vein. Expression of human ANP in SHR was identified in the heart, lung, and kidney by radioimmunoassay and reverse transcription-polymerase chain reaction followed by Southern blot analysis. A single injection of naked ANP plasmid DNA (12.3 kb) caused a significant reduction of systemic blood pressure in young SHR (4 weeks old), and the effect continued for 7 weeks. The differences were significant at 1 to 2 weeks (n = 6, P < .05) and 3 to 6 weeks after injection (n = 6, P < .01) A maximal blood pressure reduction of 21 mm Hg in young SHR was observed 5 weeks after injection with ANP DNA (159.4 +/- 3.02 mm Hg, mean +/- SEM, n = 6) compared with SHR injected with vector DNA alone (180.2 +/- 3.02 mm Hg, mean +/- SEM; n = 6; P < .01). Somatic gene delivery of human ANP DNA had no effect on the blood pressure of adult SHR (12 weeks old). After ANP gene delivery, there were significant increases in urinary volume and urinary potassium output (n = 6, P < .05) but not in body weight, heart rate, water intake, urinary sodium output, urinary creatine, and urinary protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Age Factors↗
Vaccine-preventable disease and immunization in the developing world.
Vaccines have given health care providers control over a substantial portion of the morbidity and mortality in the developing world. Global efforts have immunized two-thirds of the world's children with DTP and polio vaccines; 72% have received BCG and 59% measles vaccine; but only 29% of pregnant women have received two doses of tetanus toxoid. In addition, vaccines against yellow fever, Japanese encephalitis, hepatitis B, rubella, and mumps and meningococcal polysaccharide vaccine are being used in specific regions of the world. New vaccine candidates will enhance the vaccine armamentarium over the next decade to include the causes of pneumonia, diarrhea, and meningitis: Haemophilus influenzae type b, pneumococcal and meningococcal protein conjugate vaccines, typhoid and rotavirus vaccine. Genetically engineered vaccine vehicles, genetic reassortants, and genetic deletions are being investigated as new vaccine candidates.
Child↗
Size and shape of the model lipoprotein complex formed between glucagon and dimyristoylglycerophosphocholine.
Glucagon forms water-soluble lipoprotein particles with dimyristoylglycerophosphocholine at temperatures below the phase-transition temperature of the lipid. The shape and size of this lipoprotein particle were studied by viscometry, sedimentation velocity, sedimentation equilibrium, quasielastic light scattering, and electron microscopy using both negative-staining and freeze-fracture techniques. The lipoprotein particle has an oblate ellipsoid shape with dimensions of 250 X 70 A and an approximate molecular weight of 1.4 X 106. This molecular weight is similar to that found for small unilamellar phospholipid vesicles but is achieved in the presence of glucagon without sonication. The shape of the glucagon lipoprotein particle is similar to that found for the complex formed between some serum apolipoproteins and dimyristoylglycerophosphocholine. From these data, a model for the glucagon-dimyristoylglycerophosphocholine is proposed consisting of a single bilayer of phospholipid with the glucagon incorporated into the bilayer structure in such a manner as not greatly to disturb the average area occupied per phospholipid molecule.
Glucagon↗