In Vivo Formation of Oxidatively Modified Low-Density Lipoprotein and Its Inhibitory Effects on Cholesteryl Ester Hydrolases in the Rat.

Maehira, Fusako; Yonaha, Mari; Nakazono, Naoko; Miyagi, Ikuko; Shinjoh, Sumie

doi:10.3164/jcbn.16.37

Cited by 3 publications

(5 citation statements)

References 28 publications

(31 reference statements)

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“…3C, lane 2) with free radicals present in the lipid portion of the LDL as evidenced by reactivity with TBA and by the conjugated diene content. Similar alterations of apo-B have been reported based on both in vitro incubation with the CS extract [14,23] and in vivo formation by administrating autoxidized linoleic acid hydroperoxide to rats [23]. The generation of hydroxyl radicals from lipid hydroperoxides present in LDL oxidatively modified in vitro has recently been demonstrated by electron-spin resonance spectrometry [24].…”

Section: Resultssupporting

confidence: 67%

Tobacco Smoke Exposure Alters Cholesteryl Esterase Activities and Causes Accumulation of Cholesteryl Esters in the Rat Aorta.

Maehira

Miyagi

Kawano

et al. 1995

J. Clin. Biochem. Nutr.

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The mechanism responsible for the atherogenic effects of passive smoking was studied. Four weeks and 12 weeks of exposure of rats to tobacco sidestream smoke resulted in an increase in lipid peroxide contents, expressed as thiobarbituric-acid reactive substances, in lowdensity lipoprotein (LDL) and in aortic tissue. The LDL isolated from plasma exhibited elevations of 136, 155, and 170% over the control values for TBA, cholesterol, esterified cholesterol, respectively, whereas the corresponding increases in the aorta were 118, 148, and 254%, respectively. Electrophoretic examinations of LDL revealed a typical denatured LDL. Among esterified cholesterol-metabolizing enzymes in the aorta, lysosomal acid cholesteryl ester hydrolase, microsomal neutral cholesteryl ester hydrolase, and aryl coenzyme A : cholesterol acyltransferase were significantly suppressed by the 4 weeks' exposure; and further suppression of the acid cholesteryl ester hydrolase activity along with increases in the neutral cholesteryl ester hydrolase and acyl coenzyme A : cholesterol acyltransferase activities was observed after 12 weeks' exposure. A possible mechanism of the observed lipid accumulation in the aorta was discussed in connection with the effect of lipid peroxides in oxidatively modified-LDL on esterified cholesterol-metabolizing enzymes.

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Section: Resultssupporting

confidence: 67%

Tobacco Smoke Exposure Alters Cholesteryl Esterase Activities and Causes Accumulation of Cholesteryl Esters in the Rat Aorta.

Maehira

Miyagi

Kawano

et al. 1995

J. Clin. Biochem. Nutr.

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“…1). This finding suggests that AO introduced by passive smoking into the blood is incorporated into cells through Ox-LDL which then inhibits the intracellular CEH (18,19) and their activating enzymes (9), thereby resulting in an increased cellular content of CE.…”

Section: Discussionmentioning

confidence: 97%

“…There are three functional enzymes in this scheme: lysosomal ACEH, which degrades blood-derived exogenous CE to cholesterol; ACAT, which esterifies cholesterol to endogenous CE as a storage form by stimulation due to an increase in the intracellular cholesterol pool; and microsomal NCEH, which hydrolyzes endogenous CE. Although we have demonstrated the loss of ACEH and NCEH activity as a result of their exposure to oxidants both in vivo and in vitro (9,18,19,22), cloning of human ACEH has revealed the presence of cysteine within the mature protein (36), and the involvement of cysteine residues in the catalytic activity of ACEH has been recently clarified (37). On the other hand, evidence currently available for the presence of cysteine residues in NCEH is scant and controversial, in that the rat hepatic NCEH has been cloned and found to be a 66 kDa protein with no cysteine residues showing great overall homology with liver carboxyesterases (38,39), while the rat hepatic microsomal NCEH has been highly purified and found to be a 106 kDa protein with 30 cysteine groups exhibiting inactivation by the free sulfhydrylreacting reagents (40).…”

Section: Discussionmentioning

confidence: 97%

“…Heparinized blood was obtained from each rat by heart-puncture under Nembutal anesthesia. Aliquots (2 mL) of plasma from each rat were pooled for each group, and LDL was fractionated from the pooled plasma in the presence of 0.002% (wt/vol) BHT and 0.01% (wt/vol) EDTA by discontinuous gradient ultracentrifugation at 4°C, 250,000 × g for 48 h (18). The thoracic-to-abdominal aortae (from which other tissues were removed) were kept at −80°C until assayed.…”

Section: Methodsmentioning

confidence: 99%

“…Both in vivo and in vitro inactivation of CEH in the aorta and liver was also observed in air-oxidized linoleate hydroperoxide (LHPO)-fed rats (18) and in an enzyme assay system with the addition of LHPO or LDL isolated from LHPO-fed rats (18,19), respectively. These studies suggest that oxidative inactivations of lipolytic enzymes may contribute to the extraor intracellular increases of lipids.…”

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confidence: 94%

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Effects of passive smoking on the regulation of rat aortic cholesteryl ester hydrolases by signal transduction

Maehira

Zaha

Miyagi

et al. 2000

Lipids

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The effects of exogenous oxidative stress due to passive smoking on cholesteryl ester (CE)-metabolizing enzymes and their regulatory kinases were examined by exposing rats to cigarette smoke (CS) for a 1-h period twice a day for 8, 12, or 20 wk. An oxidatively modified low density lipoprotein (Ox-LDL) with a high lipid peroxide was identified in three CS groups after all three exposure periods. The rat aortic acid and neutral CE hydrolases (ACEH and NCEH) were activated to similar extents by both cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) in the presence of their respective cofactors. The aortic PKC activity in the three CS groups exhibited significant reductions of 72, 84, and 75% as compared with the respective controls, which coincided with the reductions in the ACEH activities (86, 71, and 80%, respectively), whereas the PKA activities increased to 121, 197, and 252% in the three CS groups, respectively. Reflecting the increase of the PKA activity, the NCEH activity exhibited increases of 112% at 8 wk and 140% until 12 wk of exposure and decreased by 50% of the control value at 20 wk of exposure, suggesting inactivation of NCEH itself. The activation of acyl-CoA:cholesterol O-acyltransferase activity was associated with an increase of free cholesterol in aorta. The vitamin E diet prevented the formation of Ox-LDL and the oxidative inactivation of most enzymes, especially PKC, until 12 wk, but was less effective by 20 wk. The oxidative inactivation of PKC, particularly its activated form that translocated to the membrane fraction, was confirmed in the in vitro exposure to active oxygen generators at an optimal concentration; this inactivation was prevented by catalase and superoxide dismutase. These results suggested that the formation of Ox-LDL and alterations in CE-metabolizing enzymes caused by passive smoking could contribute to a twofold increase in the aortic CE content, thereby contributing to one of the mechanisms for atherosclerosis associated with smoking.

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Age-related changes in the activation of aortic cholesteryl ester hydrolases by protein kinases in rats

Maehira¹,

Harada²,

Shimoji³

et al. 1998

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metaboli

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In Vivo Formation of Oxidatively Modified Low-Density Lipoprotein and Its Inhibitory Effects on Cholesteryl Ester Hydrolases in the Rat.

Cited by 3 publications

References 28 publications

Tobacco Smoke Exposure Alters Cholesteryl Esterase Activities and Causes Accumulation of Cholesteryl Esters in the Rat Aorta.

Tobacco Smoke Exposure Alters Cholesteryl Esterase Activities and Causes Accumulation of Cholesteryl Esters in the Rat Aorta.

Effects of passive smoking on the regulation of rat aortic cholesteryl ester hydrolases by signal transduction

Age-related changes in the activation of aortic cholesteryl ester hydrolases by protein kinases in rats

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