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

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Lipids

Abstract

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-acyl-transferase 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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Abbreviations

ACAT:

acyl-CoA:cholesterol O-acyltransferase

ACEH:

acid cholesteryl ester hydrolase

AO:

active oxygen

BHT:

butylated hydroxytoluene

CE:

cholesteryl ester

CEH:

cholesteryl ester hydrolase

CS:

cigarette smoke

CSE:

rats exposed to cigarette smoke and dietary vitamin E

CSC:

control rats not exposed to cigarette smoke

G/GO:

glucose/glucose oxidase

LDL:

low density lipoprotein

LHPO:

linoleate hydroperoxide

LPO:

lipid peroxide

NCEH:

neutral cholesteryl ester hydrolase

Ox-LDL:

oxidized LDL

PKA:

protein kinase A

PKC:

protein kinase C

PP:

protein phosphatase

SOD:

Cu, Zn-superoxide dismutase

TBARS:

thiobarbituric acid-reactive substance

TG:

triglyceride

X/XO:

xanthine/xanthine oxidase

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Authors and Affiliations

  1. Laboratory of Biochemistry, Department of Health Technology, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, 903-0215, Okinawa, Japan

    Fusako Maehira, Fusako Zaha, Ikuko Miyagi, Asami Tanahara & Ayano Noho

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  1. Fusako Maehira
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  3. Ikuko Miyagi
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Correspondence to Fusako Maehira.

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Maehira, F., Zaha, F., Miyagi, I. et al. Effects of passive smoking on the regulation of rat aortic cholesteryl ester hydrolases by signal transduction. Lipids 35, 503–511 (2000). https://doi.org/10.1007/s11745-000-550-x

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  • DOI: https://doi.org/10.1007/s11745-000-550-x

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