Kinetics and mechanism of the spontaneous transfer of fluorescent phosphatidylcholines between apolipoprotein-phospholipid recombinants

Massey, John B.; Gotto, Antonio M.; Pownall, Henry J.

doi:10.1021/bi00258a016

Cited by 119 publications

(85 citation statements)

References 32 publications

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“…The rate-limiting step for spontaneous lipid transfer from particle surfaces is desorption, 38,39 which follows Kelvin’s law stating that desorption halftimes are a positive function of particle radius. 40,41 Differences in particle shape—HDL is a sphere and nHDL is a disc, and composition—nHDL and HDL are 60 (Table 1) and 10 mol% FC, 42 play unknown roles.…”

Section: Discussionmentioning

confidence: 99%

ABCA1-Derived Nascent High-Density Lipoprotein–Apolipoprotein AI and Lipids Metabolically Segregate

Gillard

Gotto

et al. 2017

ATVB

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Objective Reverse cholesterol transport (RCT) comprises cholesterol efflux from ABCA1-expressing macrophages to apo AI giving nascent high density lipoprotein (nHDL), esterification of nHDL-free cholesterol (FC), selective hepatic extraction of HDL-lipids, and hepatic conversion of HDL-cholesterol to bile salts, which are excreted. We tested this model by identifying the fates of nHDL-[3H]FC, [14C]PL, and [125I]apo AI in serum in vitro and in vivo. Approach and Results During in vitro incubation of human serum, nHDL-[3H]FC and [14C]PL rapidly transfer to HDL and low density lipoproteins (LDL; t1/2 = 2–7 min) while nHDL-[125I]apo AI transfers solely to HDL (t1/2<10 min) and to the lipid-free form (t1/2 >480 min). Following injection into mice nHDL-[3H]FC and [14C]PL rapidly transfer to liver (t1/2 ~ 2–3 min) whereas apo AI clears with t1/2 = ~460 min. The plasma nHDL-[3H]FC esterification rate is slow (0.46%/h) compared to hepatic uptake. Phospholipid transfer protein enhances nHDL-[14C]PL but not nHDL-[3H]FC transfer to cultured Huh7 hepatocytes. Conclusions nHDL-FC, PL, and apo AI enter different pathways in vivo. Most nHDL-[3H]FC and [14C]PL are rapidly extracted by the liver via scavenger receptor class B member 1 and spontaneous transfer; hepatic PL uptake is promoted by phospholipid transfer protein. nHDL-[125I]apo AI transfers to HDL and to the lipid-free form that can be recycled to nHDL formation. Cholesterol esterification by LCAT is a minor process in nHDL metabolism. These findings could guide the design of therapies that better mobilize peripheral tissue-FC to hepatic disposal.

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Section: Discussionmentioning

confidence: 99%

ABCA1-Derived Nascent High-Density Lipoprotein–Apolipoprotein AI and Lipids Metabolically Segregate

Gillard

Gotto

et al. 2017

ATVB

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“…Pyrene fluorescence excimer (dimer) formation was used to study the lateral diffusion in the membrane following the method of Massey et al (1982). r I I I I I I I I II II II s II …”

Section: Measurement Of Membrane Microviscosity Using Pyrene As An Exmentioning

confidence: 99%

Chemopreventive Effects of Nonsteroidal Anti-Inflammatory Drugs in the Membrane Lipid Composition and Fluidity Parameters of the 1,2-Dimethylhydrazine-Induced Colon Carcinogenesis in Rats

Kanwar

Vaiphei

Nehru

et al. 2007

Drug and Chemical Toxicology

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Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, celecoxib, and etoricoxib are reported to act as chemopreventive agents in experimental colon cancer induced by 1,2-dimethylhydrazine (DMH) as they are known cyclooxygenase (COX) enzyme inhibitors. To determine whether NSAIDs can also effectively modulate the membrane lipid compositions and the fluidity parameters of colonic brush border membrane, rats were injected subcutaneously (s.c.) with DMH 30 mg/kg body weight per week for 6 weeks. The animals were simultaneously treated with NSAIDs orally at the dose of aspirin, 60 mg/kg body weight; celecoxib, 6 mg/kg body weight; and etoricoxib, 0.6 mg/kg body weight. The animals were sacrificed after 6 weeks of treatments. Brush border membrane was isolated from proximal and distal portions of the colon. Membrane lipids were extracted and analyzed while the fluidity parameters were assessed by steady-state fluorescence polarization technique using the membrane extrinsic fluorophore 1,6-diphenyl-1,3,5-hexatriene (DPH). The translational diffusion was measured by using the excimer formation of pyrene incorporated in the membrane. Colonic mucosal changes in DMH alone and DMH+NSAID treated animals were assessed histologically. The results demonstrate that (a) there is a distinct occurrence of premalignant alterations in DMH-induced colon in the form of multiple plaque lesions (MPLs), which were greatly reduced by the NSAIDs used, (b) the membrane lipid changes in DMH-induced colon were completely restored back, (c) the alterations in membrane fluorescence polarization and the fluidity parameters are partially recovered, particularly with etoricoxib, and (d) the pyrene excimer formation process was completely restored. It may be concluded that the NSAIDs, particularly the coxib group of the drugs (COX-2 selective), are effective in chemoprevention in the DMH-induced colon carcinogenesis and membrane alterations.

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“…These lipids carry a pyrenylacyl chain in either the sn-1 or sn-2 position and an unlabeled acyl chain in the other position. Similar lipids have been used by others to study either passive or protein-mediated phospholipid transfer (Charlton et al, 1978;Doody et al, 1980;Roseman & Thompson, 1980;Massey et al, 1982Massey et al, , 1984Massey et al, , 1985. By varying the position and the length of the pyrenylacyl and unlabeled acyl chain, one can systematically probe the sn-1 and sn-2 acyl binding sites of the protein.…”

mentioning

confidence: 99%

Properties of the binding sites for the sn-1 and sn-2 acyl chains on the phosphatidylinositol transfer protein from bovine brain

Paridon¹,

Gadella²,

Somerharju³

et al. 1988

Biochemistry

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Kinetics and mechanism of the spontaneous transfer of fluorescent phosphatidylcholines between apolipoprotein-phospholipid recombinants

Cited by 119 publications

References 32 publications

ABCA1-Derived Nascent High-Density Lipoprotein–Apolipoprotein AI and Lipids Metabolically Segregate

ABCA1-Derived Nascent High-Density Lipoprotein–Apolipoprotein AI and Lipids Metabolically Segregate

Chemopreventive Effects of Nonsteroidal Anti-Inflammatory Drugs in the Membrane Lipid Composition and Fluidity Parameters of the 1,2-Dimethylhydrazine-Induced Colon Carcinogenesis in Rats

Properties of the binding sites for the sn-1 and sn-2 acyl chains on the phosphatidylinositol transfer protein from bovine brain

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