AJP - Heart Calcium Transients and Cell-Sarcomere
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 274: H1836-H1840, 1998;
0363-6135/98 $5.00
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Qin, X.
Right arrow Articles by Tso, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Qin, X.
Right arrow Articles by Tso, P.
Vol. 274, Issue 5, H1836-H1840, May 1998

RAPID COMMUNICATION
Apolipoprotein AIV: a potent endogenous inhibitor of lipid oxidation

Xiaofa Qin, Debi K. Swertfeger, Shuqin Zheng, David Y. Hui, and Patrick Tso

Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0529

    ABSTRACT
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References

Overexpression of apolipoprotein (apo) AIV in transgenic mice confers significant protection against atherosclerosis in apoE knockout animals even in the presence of a more severe atherogenic lipid profile. Because lipoprotein oxidation has been recognized to be pivotal in development of atherosclerosis, the antioxidative activity of apoAIV was investigated. Fasting intestinal lymph was used to mimic conditions in the interstitial fluid, the potential site for lipoprotein oxidation in vivo. ApoAIV (10 µg/ml) significantly inhibited copper-mediated oxidation of lymph. This inhibitory effect was further evaluated using purified low-density lipoprotein. Addition of apoAIV (2.5 µg/ml) increased the time of 50% conjugated diene formation by 2.4-fold, whereas apoE or BSA did not show such a protection even at 20 µg/ml. Addition of apoAIV during the propagation phase also resulted in a dose-dependent inhibition. ApoAIV also protected macrophage-induced oxidation of fasting lymph. These results provide the first evidence that apoAIV is a potent endogenous antioxidant.

antioxidative activity; lipoprotein oxidation; lymph; interstitial fluid; atherosclerosis

    INTRODUCTION
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References

APOLIPOPROTEIN AIV (apoAIV) is a 46-kDa plasma protein that circulates freely in solution or associates with chylomicrons and high-density lipoprotein (HDL). Although apoAIV is a major circulating apolipoprotein, its physiological function is not totally clear. Two recent studies have shown that overexpression of either human or mouse apoAIV in transgenic mice confers significant protection against diet-induced atherosclerosis in cholesterol-fed animals and apoE-deficient mice (2, 4). These results suggest that apoAIV may play a protective role against atherosclerosis. However, the mechanism of apoAIV protection against atherosclerosis remains speculative.

Based on previous in vitro observations, several functions have been ascribed to this apolipoprotein. For example, apoAIV has been shown to 1) promote cholesterol efflux from extrahepatic tissues (20), 2) serve as a ligand for HDL binding to hepatocytes (5), 3) activate lecithin:cholesterol acyltransferase (6), and 4) modulate the activation of lipoprotein lipase by apoCII (8). However, these functions can also be fulfilled by other apolipoproteins, particularly apoAI. Although experiments with apoAI transgenic mice also showed a protective effect against atherosclerosis in cholesterol-fed and apoE-deficient mice (18), the lipoprotein profiles of apoAI- versus apoAIV-transgenic mice are quite different. It appears that transgenic expression of human apoAI suppresses atherosclerosis in apoE-deficient mice by increasing HDL (18). In contrast, the protective effect of apoAIV in apoE-deficient mice was observed despite a more severe atherogenic lipid profile, i.e., increased total plasma cholesterol with no significant change for HDL cholesterol (4). Thus the protective effect of apoAIV may be different from that of apoAI. One unique function of apoAIV that is not shared by other apolipoproteins is its role as a satiety factor (7). However, overexpression of human apoAIV in transgenic mice did not affect their feeding behavior (2, 4), suggesting that apoAIV protection against atherosclerosis in this animal model is also independent of its effect on food intake. Taken together, these results suggest that apoAIV may have yet another physiological function that confers protection against atherosclerosis. This protective mechanism is probably independent of lipoprotein metabolism and food intake.

A hallmark of atherosclerosis is the presence of oxidized lipids in lipoproteins and in the lesions (1, 21). Oxidized lipoproteins may also enhance lesion formation by increasing lipid deposition in macrophages and inducing proatherogenic cellular responses in the vessel wall (1). How endogenous factors influence the oxidative modifications of lipoproteins remains largely unknown. In view of observations demonstrating the involvement of lipoprotein oxidation in atherosclerosis of apoE-deficient mice (17), this study was undertaken to assess the potential role of apoAIV in protection against lipid oxidation.

A potential site for lipoprotein oxidation is the subendothelial space, and fasting intestinal lymph was used as the substrate for copper-induced oxidation to mimic conditions in the interstitial fluid. The protective effects of apoAIV against copper-induced oxidation of purified low-density lipoprotein (LDL) as well as macrophage-mediated oxidation of fasting intestinal lymph were also studied.

    MATERIALS AND METHODS
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References

Purification of Apolipoproteins

Apolipoproteins were isolated from rat plasma lipoproteins by preparative PAGE as previously described (11) except that the final purified apolipoproteins were dialyzed against four changes of a dialysis buffer containing 20 mM Tris · HCl (pH 7.4) and 0.14 M NaCl at 4°C.

Collection of Intestinal Lymph

Sprague-Dawley rats (275-300 g) were fasted overnight. Intestinal lymph duct and duodenal cannulations were performed as described previously (22). After the surgery, rats were infused intraduodenally with a glucose-saline solution containing 0.28 M glucose, 145 mM NaCl, and 4 mM KCl, and intestinal lymph was collected over ice.

Purification of LDL

Human LDL (density = 1.019-1.063 g/ml) was isolated from the plasma of normal blood donors by density gradient ultracentrifugation as previously described (10) and stored in saline-EDTA. Just before use, EDTA was eliminated by dialysis against PBS, and the concentration of LDL is expressed in milligrams of protein as determined by Lowry assay.

Assay of Lipid Oxidation

Assay of thiobarbituric acid-reactive substances. A thiobarbituric acid-reactive substances (TBARS) assay for purified LDL was performed using a method modified from that of Hulea et al. (12). Briefly, 0.4 ml of solution containing 20 µg LDL, 0.02 M Tris (pH 7.4), 0.14 M NaCl, 10 µM CuSO4, and different amounts of apolipoproteins was incubated for 3 h at 37°C. After incubation, 0.1 ml of 25% TCA and 0.5 ml 1% thiobarbituric acid (in 50% acetic acid) were added and heated at 95°C for 45 min. The solution was centrifuged at 13,000 rpm (Hermle Microcentrifuge, model Z180M) for 10 min, and the supernatant was read at 532 nm. For the incubation with fasting lymph, we found that 100 µM copper caused the formation of the maximal amount of TBARS under our experimental condition. Consequently, 100 µM copper was used in all subsequent lymph incubation experiments. We also studied the influence of the amount of lymph in the incubation medium and the amount of TBARS formed and found a linear relationship between the two at <= 20 µl of lymph. Therefore, we used 20 µl of fasting lymph in all subsequent incubation experiments. The final composition of the reaction mixture (0.4 ml) for the TBARS assay of the fasting lymph contained 20 µl of fasting lymph, 100 µM CuSO4, 0.02 M Tris (pH 7.4), 0.14 M NaCl, and different amounts of apolipoprotein.

Macrophage-mediated oxidation of lymph. For assay of the macrophage- mediated oxidation of fasting lymph, peritoneal macrophages were collected from C57BL/6 mice by intraperitoneal injection of 5 ml of DMEM with 10% fetal bovine serum. Cells (2 × 106) were added to each well of a 24-well plate. After 2 h of incubation at 37°C in 95% air-5% CO2, the nonadherent cells were removed by three washes with DMEM. F-10 medium (0.5 ml) was added to each well, followed by 5 µl fasting lymph and 10 µg apoAIV (50 µl of a saline solution containing 200 µg/ml apoAIV). After 12 h of incubation, an aliquot of supernatant was taken from each well and assayed for TBARS.

Assay of Formation of Conjugated Dienes During Copper-Mediated Oxidation of LDL

Conjugated diene formation during copper-mediated oxidation of LDL was measured by monitoring the formation of conjugated dienes (14). Briefly, LDL (50 µg/ml), with or without additional apolipoproteins or BSA, was oxidized using 10 µM CuSO4 at 30°C in a quartz cuvette, and absorbency readings at 234 nm were taken every 5 min.

Statistics

Data are expressed as means ± SE. Statistical analysis was performed using the Student's t-test. Differences were considered significant at P < 0.05.

    RESULTS
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References

Inhibition of Copper-Mediated Oxidation of Fasting Lymph by ApoAIV

Addition of apoAIV inhibited the oxidation of lymph lipids in a dose-dependent manner, with significant inhibition observed at concentrations >= 10 µg/ml (Fig. 1). One possible mechanism for this effect is apoAIV chelating with copper ions, thus leaving little free copper to initiate the lipid peroxidation process. To test this possibility, we dialyzed apoAIV extensively against a 100 µM copper solution to saturate all the binding sites of the protein. The treated apoAIV (dialyzed against copper solution) did not show a significant decrease in its ability to prevent the oxidation of lymph lipoproteins compared with the nontreated apoAIV (data not shown). Thus it is highly unlikely that the inhibitory effect of apoAIV against copper-induced lipid peroxidation is due to the formation of apoAIV-copper complex. The protection against lipid oxidation by apoAIV is physiologically relevant because the maximal protection against lipid oxidation was achieved at an apoAIV concentration that is at least 2-fold lower than its concentration in lymph and 10- to 20-fold lower than its concentration in plasma (100-200 µg/ml).


View larger version (15K):
[in this window]
[in a new window]
  		Fig. 1.   Inhibition of copper-mediated oxidation of fasting lymph and low-density lipoprotein (LDL) by different doses of apolipoprotein (apo) AIV. Fasting intestinal lymph or LDL was oxidized in absence or presence of apoAIV at concentration indicated. Fasting lymph from 3 different animals was oxidized by 100 µM CuSO4 for 3 h at 37°C (bullet ). LDL (50 µg/ml) was oxidized by 10 µM CuSO4 for 3 h at 37°C (open circle ). Protection against thiobarbituric acid-reactive substances (TBARS) formation by apoAIV is expressed as %reduction in amount of TBARS formed compared with amount of TBARS formed in absence of apoAIV. Values are expressed as means ± SE of 3 experiments. * P < 0.05, ** P < 0.01 vs. control.

Inhibition of Copper-Mediated Oxidation of LDL by ApoAIV

The antioxidative effect of apoAIV was not limited to fasting lymph lipoproteins but was also effective toward LDL. Results showed that apoAIV was also effective in inhibiting copper-induced LDL oxidation (Fig. 1). The inhibition was dose dependent, with a significant inhibition observed at 5 µg/ml apoAIV (Fig. 1). This inhibition was also verified by monitoring the formation of conjugated dienes. As shown in Fig. 2, the addition of 2.5 µg/ml apoAIV increased the time of 50% conjugated diene formation (T1/2) by 2.4-fold. Conjugated diene formation was not observed in the presence of 20 µg/ml of apoAIV (Fig. 2). In contrast, rat apoE, even at concentrations of 20 µg/ml, increased T1/2 by only 1.3-fold (Fig. 2). This result is consistent with the observation by Miyata and Smith (15), who observed that the addition of 20 µg of apoE4, E3, and E2 in the reaction mixture resulted in only a 1.47-, 1.55-, and 1.75-fold increase, respectively, of T1/2 in conjugated diene formation.


View larger version (26K):
[in this window]
[in a new window]
  		Fig. 2.   Kinetics of LDL oxidation in presence or absence of apolipoproteins. LDL (50 µg/ml) was oxidized using 10 µM CuSO4 at 30°C in a quartz cuvette. Absorbance readings at 234 nm (A234) were taken every 5 min to measure formation of conjugated dienes. Conjugated diene formation in LDL was determined in presence of 2.5 µg/ml apoAIV (×), 20 µg/ml apoAIV (open circle ), 20 µg/ml apoE (triangle ), 20 µg/ml BSA (), or buffer only (square ).

The antioxidative effects of apoAIV were further explored by determining whether apoAIV could also inhibit LDL oxidation during the propagation phase of the oxidative process. As shown in Fig. 3, addition of apoAIV during the propagation phase resulted in a dose-dependent inhibition of LDL oxidation. A linear inverse relationship (R2 = 0.9955) was observed between the change in the rate of conjugated diene formation and the amount of apoAIV added during the reaction (Fig. 3, inset). These results suggested a direct effect of apoAIV in interfering with the oxidation.


View larger version (35K):
[in this window]
[in a new window]
  		Fig. 3.   Inhibitory effect of apoAIV during propagation phase of LDL oxidation. LDL oxidation, monitored by conjugated diene assay, was allowed to proceed to propagation phase of oxidation. ApoAIV was then added to oxidation reaction during propagation phase, and conjugated dienes were continuously measured in samples containing only LDL (square ), LDL plus Tris-saline (×), LDL plus 5 µg/ml apoAIV (triangle ), LDL plus 10 µg/ml apoAIV (open circle ), and LDL plus 20 µg/ml apoAIV (bullet ). Inset: change in slope after addition of apoAIV.

Inhibition of Macrophage-Mediated Oxidation of Fasting Lymph by ApoAIV

To examine the antioxidative capacity of apoAIV in an in vivo system, macrophage-mediated oxidation of lymph lipoproteins was used. As shown in Fig. 4, apoAIV (20 µg/ml) showed an 85% inhibition in macrophage-mediated oxidation of fasting lymph. These results imply that apoAIV may serve as an antioxidant in vivo, where the oxidation of lipoproteins by macrophages in the subendothelial space has been suggested to play a key role in the development of atherosclerosis.


View larger version (26K):
[in this window]
[in a new window]
  		Fig. 4.   ApoAIV inhibits macrophage-mediated oxidation of fasting lymph. Generation of TBARS (nmol/ml of culture medium) by peritoneal macrophages incubated in presence and absence of lymph and/or apoAIV is shown. Each experiment was performed in quadruplicate, and results are expressed as means ± SE. Cells only: peritoneal macrophage in 0.5 ml F-10 medium; cells + lymph: addition of 5 µl fasting lymph in culture medium; cells + lymph + apoAIV: 5 µl fasting lymph plus 10 µg apoAIV added to culture medium; and medium + lymph: 5 µl of fasting lymph added to medium. ** P < 0.01 vs. cell + lymph.

    DISCUSSION
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References

These data demonstrate that apoAIV is a potent antioxidant of lymph lipoproteins. Although many antioxidants exist in nature, apoAIV is unique in the following important aspects. 1) Unlike exogenous antioxidants such as alpha -tocopherol, ascorbate, and beta -carotene, apoAIV is synthesized in the body and thus serves as a naturally occurring potent anti-oxidant. 2) ApoAIV is mainly produced by the intestine, and its production is directly correlated with fat intake. ApoAIV synthesis increases with high fat consumption (13, 16). In contrast, other apolipoproteins produced by the gastrointestinal tract such as apoAI and apoB are not affected by lipid feeding. In fact, the apoAIV levels remain elevated even after the postprandial hypertriglyceremia period (16). This prolonged increase in apoAIV production may represent a natural response in the body to guard against lipid oxidation and the generation of deleterious lipid peroxidation products during both the absorption and postprandial periods. 3) Unlike most other antioxidants, apoAIV is amphipathic and is distributed in lipoprotein-bound and lipoprotein-free forms in circulation (3). These characteristics allow apoAIV to exert its antioxidative activity in both lipid and aqueous phases. 4) The level of lymphatic apoAIV protein has been shown to be significantly higher in cholesterol-fed dogs versus control animals (19). The increase of apoAIV was detected in very low-density lipoproteins, LDL, HDL, and in lipoprotein-free fractions of the lymph, in contrast to decreases of apoAI in each fraction (19). The apoAIV concentration of lymph of the cholesterol-fed dogs was more than twice the plasma apoAIV level. The higher apoAIV level in the interstitial fluid than in plasma would allow apoAIV to be more effective in guarding against oxidative modification of lipoproteins in places where they are mostly likely to occur. In view of observations that apoAIV is a more potent antioxidant than apoE, a well established antiatherogenic protein (15), the results suggest that therapeutic treatment aimed at increasing apoAIV levels may be a fruitful strategy for the reduction of coronary heart disease.

We can conclude from this study that apoAIV is a potent antioxidant produced by the small intestine to guard against lipoprotein oxidation in the body. This study provides a plausible explanation for the observation that apoAIV transgenic animals, when mated with apoE knockout animals, confer protection against atherosclerosis. Similarly, the protection against lipoprotein oxidation may also explain the protection in apoAIV transgenic mice against atherosclerosis following the feeding of an atherogenic diet.

    ACKNOWLEDGEMENTS

The authors thank J. L. Goldstein (University of Texas Southwestern Medical School, Dallas, TX) for review of this manuscript.

    FOOTNOTES

This research was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants DK-32288 (P. Tso) and DK-46405 (D. Y. Hui).

Address for reprint requests: P. Tso, Dept. of Pathology and Laboratory Medicine, Univ. of Cincinnati College of Medicine, 231 Bethesda Ave. (ML 0529), Cincinnati, OH 45267-0529.

Received 24 November 1997; accepted in final form 18 February 1998.

    REFERENCES
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References

1.   Chisolm, G. M., III, and M. S. Penn. Oxidized lipoproteins and atherosclerosis. In: Atherosclerosis and Coronary Artery Disease, edited by V. Fuster, R. Ross, and E. J. Topol. Philadelphia, PA: Lippincott-Raven, 1996, vol. 1, p. 129-149.

2.   Cohen, R. D., L. W. Castellani, J. H. Qiao, B. J. V. Lenten, A. J. Lusis, and K. Reue. Reduced aortic lesions and elevated high density lipoprotein levels in transgenic mice overexpressing mouse apolipoprotein A-IV. J. Clin. Invest. 99: 1906-1916, 1997[Medline].

3.   Dallinga-Thie, G. M., A. van Tol, F. M. van't Hooft, and P. H. Groot. Distribution of apolipoproteins A-I and A-IV among lipoprotein classes in rat mesenteric lymph, fractionated by molecular sieve chromatography. Biochim. Biophys. Acta 876: 108-115, 1986[Medline].

4.   Duverger, N., G. Tremp, J. M. Caillaud, F. Emmanuel, G. Castro, J. C. Fruchart, A. Steinmetz, and P. Denefle. Protection against atherogenesis in mice mediated by human apolipoprotein AIV. Science 273: 966-968, 1996[Abstract].

5.   Dvorin, E., N. L. Gorder, D. M. Benson, and A. M. J. Gotto. Apolipoprotein A-IV. A determinant for binding and uptake of high density lipoproteins by rat hepatocytes. J. Biol. Chem. 261: 15714-15718, 1986[Abstract/Free Full Text].

6.   Emmanuel, F., A. Steinmetz, M. Rosseneu, R. Brasseur, N. Gosselet, F. Attenot, S. Cuine, S. Seguret, M. Latta, J. C. Fruchart, and P. Denefle. Identification of specific amphipathic alpha-helical sequence of human apolipoprotein A-IV involved in lecithin:cholesterol acyltransferase activation. J. Biol. Chem. 269: 29883-29890, 1994[Abstract/Free Full Text].

7.   Fujimoto, K., J. A. Cardelli, and P. Tso. Increased apolipoprotein A-IV in rat mesenteric lymph after lipid meal acts as a physiological signal for satiation. Am. J. Physiol. 262 (Gastrointest. Liver Physiol. 25): G1002-G1006, 1992[Abstract/Free Full Text].

8.   Goldberg, I. J., C. A. Scheraldi, L. K. Yacoub, U. Saxena, and C. L. Bisgaier. Lipoprotein ApoC-II activation of lipoprotein lipase. Modulation by apolipoprotein A-IV. J. Biol. Chem. 265: 4266-4272, 1990[Abstract/Free Full Text].

9.   Green, P. H., R. M. Glickman, J. W. Riley, and E. Quinet. Human apolipoprotein A-IV. Intestinal origin and distribution in plasma. J. Clin. Invest. 65: 911-919, 1980.

10.   Havel, R. J., H. A. Eder, and J. H. Bragdon. Distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J. Clin. Invest. 34: 1345-1353, 1955.

11.   Hayashi, H., D. F. Nutting, K. Fujimoto, J. A. Cardelli, D. Black, and P. Tso. Transport of lipid and apolipoproteins A-I and A-IV in intestinal lymph of the rat. J. Lipid Res. 31: 1613-1625, 1990[Abstract].

12.   Hulea, S. A., E. Waswicz, and F. A. Kummerow. Inhibition of metal-catalyzed oxidation of low-density lipoprotein by free and albumin-bound bilirubin. Biochim. Biophys. Acta 1259: 29-38, 1995[Medline].

13.   Kalogeris, T. J., K. Fukagawa, and P. Tso. Synthesis and lymphatic transport of intestinal apolipoprotein A-IV in response to graded doses of triglyceride. J. Lipid Res. 35: 1141-1151, 1994[Abstract].

14.   Kleinveld, H. A., H. L. M. Hak-Lemmers, A. F. H. Stalenhoef, and P. N. M. Demacker. Improved measurement of low-density-lipoprotein susceptibility to copper-induced oxidation: application of a short procedure for isolating low-density lipoprotein. Clin. Chem. 38: 2066-2072, 1992[Abstract].

15.   Miyata, M., and J. D. Smith. Apolipoprotein E allele-specific antioxidant activity and effects on cytotoxicity by oxidative insults and beta-amyloid peptides. Nat. Genet. 14: 55-61, 1996[Medline].

16.   Miyata, Y., S. Koga, and H. Ibayashi. Alterations in plasma levels of apolipoprotein A-IV in various clinical entities. Gastroenterol. Jpn. 21: 479-485, 1986[Medline].

17.   Palinski, W., V. A. Ord, A. S. Plump, J. L. Breslow, D. Steinberg, and J. L. Witztum. Apo E-deficient mice are a model of lipoprotein oxidation in atherogenesis. Arterioscler. Thromb. 14: 605-616, 1994[Abstract/Free Full Text].

18.   Plump, A. S., C. J. Scott, and J. L. Breslow. Human apolipoprotein A-I gene expression increases high density lipoprotein and suppresses atherosclerosis in the apolipoprotein E-deficient mouse. Proc. Natl. Acad. Sci. USA 91: 9607-9611, 1994[Abstract/Free Full Text].

19.   Sloop, S. H., L. Dory, B. R. Krause, C. Castle, and P. S. Roheim. Lipoproteins and apolipoproteins in peripheral lymph of normal and cholesterol-fed dogs. Arteriosclerosis 49: 91-21, 1983.

20.   Stein, O., Y. Stein, M. Lefevre, and P. S. Roheim. The role of apolipoprotein A-IV in reverse cholesterol transport studied with cultured cells and liposomes derived from an ether analog of phosphatidylcholine. Biochim. Biophys. Acta 878: 7-13, 1986[Medline].

21.   Steinberg, D., S. Parthasarathy, T. E. Carew, J. C. Khoo, and J. L. Witztum. Beyond cholesterol: modification of low-density lipoprotein that increase its atherogenicity. N. Engl. J. Med. 320: 915-923, 1989[Medline].

22.   Tso, P., M. D. Karlstad, B. R. Bistrian, and S. J. DeMichele. Intestinal digestion, absorption, and transport of structured triglycerides and cholesterol in rats. Am. J. Physiol. 268 (Gastrointest. Liver Physiol. 31): G568-G577, 1995[Abstract/Free Full Text].

AJP Heart Circ Physiol 274(5):H1836-H1840
0363-6135/98 $5.00 Copyright © 1998 the American Physiological Society


This article has been cited by other articles:


Home page
 J. Lipid Res.Home page
L. Shelly, L. Royer, T. Sand, H. Jensen, and Y. Luo
Phospholipid transfer protein deficiency ameliorates diet-induced hypercholesterolemia and inflammation in mice
J. Lipid Res., April 1, 2008; 49(4): 773 - 781.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
E. Levy, K. Trudel, M. Bendayan, E. Seidman, E. Delvin, M. Elchebly, J.-C. Lavoie, L.-P. Precourt, D. Amre, and D. Sinnett
Biological role, protein expression, subcellular localization, and oxidative stress response of paraoxonase 2 in the intestine of humans and rats
Am J Physiol Gastrointest Liver Physiol, December 1, 2007; 293(6): G1252 - G1261.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
S. Leng, S. Lu, Y. Yao, Z. Kan, G. S. Morris, B. R. Stair, M. A. Cherny, and D. D. Black
Hepatocyte nuclear factor-4 mediates apolipoprotein A-IV transcriptional regulation by fatty acid in newborn swine enterocytes
Am J Physiol Gastrointest Liver Physiol, August 1, 2007; 293(2): G475 - G483.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
H. L. Spaulding, F. Saijo, R. H. Turnage, J. S. Alexander, T. Y. Aw, and T. J. Kalogeris
Apolipoprotein A-IV attenuates oxidant-induced apoptosis in mitotic competent, undifferentiated cells by modulating intracellular glutathione redox balance
Am J Physiol Cell Physiol, January 1, 2006; 290(1): C95 - C103.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
S. Lu, Y. Yao, H. Wang, S. Meng, X. Cheng, and D. D. Black
Regulation of apo A-IV transcription by lipid in newborn swine is associated with a promoter DNA-binding protein
Am J Physiol Gastrointest Liver Physiol, February 1, 2003; 284(2): G248 - G254.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Lu, Y. Yao, S. Meng, X. Cheng, and D. D. Black
Overexpression of Apolipoprotein A-IV Enhances Lipid Transport in Newborn Swine Intestinal Epithelial Cells
J. Biol. Chem., August 23, 2002; 277(35): 31929 - 31937.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
F. Kronenberg, E. Kuen, E. Ritz, P. Konig, G. Kraatz, K. Lhotta, J. F. E. Mann, G. A. Muller, U. Neyer, W. Riegel, et al.
Apolipoprotein A-IV Serum Concentrations Are Elevated in Patients with Mild and Moderate Renal Failure
J. Am. Soc. Nephrol., February 1, 2002; 13(2): 461 - 469.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
T. Doi, M. Liu, R. J. Seeley, S. C. Woods, and P. Tso
Effect of leptin on intestinal apolipoprotein AIV in response to lipid feeding
Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2001; 281(3): R753 - R759.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
M. A. Ostos, M. Conconi, L. Vergnes, N. Baroukh, J. Ribalta, J. Girona, J.-M. Caillaud, A. Ochoa, and M. M. Zakin
Antioxidative and Antiatherosclerotic Effects of Human Apolipoprotein A-IV in Apolipoprotein E-Deficient Mice
Arterioscler. Thromb. Vasc. Biol., June 1, 2001; 21(6): 1023 - 1028.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
T. J. Kalogeris and R. G. Painter
Adaptation of intestinal production of apolipoprotein A-IV during chronic feeding of lipid
Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2001; 280(4): R1155 - R1161.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
M. Ishigami, D. K. Swertfeger, M. S. Hui, N. A. Granholm, and D. Y. Hui
Apolipoprotein E Inhibition of Vascular Smooth Muscle Cell Proliferation but Not the Inhibition of Migration Is Mediated Through Activation of Inducible Nitric Oxide Synthase
Arterioscler. Thromb. Vasc. Biol., April 1, 2000; 20(4): 1020 - 1026.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
T. J. Kalogeris, R. G. Painter, and V. R. Holden
Ileal Lipid Infusion Stimulates Jejunal Synthesis of Apolipoprotein A-IV Without Affecting mRNA Levels
Experimental Biology and Medicine, February 1, 2000; 223(2): 198 - 202.
[Abstract] [Full Text]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
Y. Stein, O. Stein, N. Duverger, G. Halperin, Y. Dabach, G. Hollander, and M. Ben-Naim
Clearance of Cationized LDL Cholesterol From a Muscle Depot Is Not Enhanced in Human Apolipoprotein A-IV Transgenic Mice
Arterioscler. Thromb. Vasc. Biol., January 1, 2000; 20(1): 179 - 184.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
T. J. Kalogeris, V. R. Holden, and P. Tso
Stimulation of jejunal synthesis of apolipoprotein A-IV by ileal lipid infusion is blocked by vagotomy
Am J Physiol Gastrointest Liver Physiol, November 1, 1999; 277(5): G1081 - G1087.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. P. Bridges, H. W. Davis, M. Damodarasamy, Y. Kuroki, G. Howles, D. Y. Hui, and F. X. McCormack
Pulmonary Surfactant Proteins A and D Are Potent Endogenous Inhibitors of Lipid Peroxidation and Oxidative Cellular Injury
J. Biol. Chem., December 1, 2000; 275(49): 38848 - 38855.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Qin, X.
Right arrow Articles by Tso, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Qin, X.
Right arrow Articles by Tso, P.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online