Chronic ethanol exposure in rats affects rabs-dependent hepatic trafficking of apolipoprotein E and transferrin

Because of the important roles of rabs in protein trafficking, we tested whether chronic ethanol exposure affected the trafficking of newly synthesized apolipoprotein E (apoE) or transferrin ( O-glycosylated and N-glycosylated proteins, respectively) attached to acylated or prenylated rabs. The in v...

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Veröffentlicht in:Alcohol (Fayetteville, N.Y.) N.Y.), 2001-11, Vol.25 (3), p.195-200
Hauptverfasser: Marmillot, Philippe, Rao, Manjunath N., Lakshman, M.Raj
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creator Marmillot, Philippe
Rao, Manjunath N.
Lakshman, M.Raj
description Because of the important roles of rabs in protein trafficking, we tested whether chronic ethanol exposure affected the trafficking of newly synthesized apolipoprotein E (apoE) or transferrin ( O-glycosylated and N-glycosylated proteins, respectively) attached to acylated or prenylated rabs. The in vivo 30-min incorporation ratios of [ 3H]palmitate:[ 35S]methionine or [ 3H]mevalonate:[ 35S]methionine (relative ratios of rabs acylation or prenylation to total protein or to immunoisolated apoE or transferrin) were measured in various hepatic subcellular organelles of 8 week-ethanol-fed (E) and pair-fed control (C) Wistar–Furth rats. With respect to total protein trafficking, ethanol increased rabs acylation ratio by 136% ( P < .01), 69% ( P < .05), and 64% ( P < .01) in the endoplasmic reticulum (ER), Golgi light fraction (GLF), and Golgi heavy fraction (GHF), respectively, and decreased this ratio by 76% ( P < .01) in carrier vesicle fraction 2 (CV2). With respect to apoE trafficking, ethanol increased rabs acylation ratio by 121% in GHF and decreased this ratio by 27% in CV2. Rabs prenylation ratio increased by 21% and 53% in GHF and CV2, respectively, and decreased by 42% in GLF. With respect to transferrin trafficking, ethanol increased rabs acylation ratio by 53% ( P < .01) in GHF, with no significant effect in ER, whereas rabs prenylation ratio increased by 26% ( P < .05) in ER, with no significant effect in GHF. Therefore, we conclude that ethanol-induced impaired trafficking of newly synthesized O- and N-glycosylated proteins occurs primarily in ER and Golgi and is due to altered lipidation of rabs, possibly rabs 1, 2, or 6 or combinations of these three rabs.
doi_str_mv 10.1016/S0741-8329(01)00179-3
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The in vivo 30-min incorporation ratios of [ 3H]palmitate:[ 35S]methionine or [ 3H]mevalonate:[ 35S]methionine (relative ratios of rabs acylation or prenylation to total protein or to immunoisolated apoE or transferrin) were measured in various hepatic subcellular organelles of 8 week-ethanol-fed (E) and pair-fed control (C) Wistar–Furth rats. With respect to total protein trafficking, ethanol increased rabs acylation ratio by 136% ( P < .01), 69% ( P < .05), and 64% ( P < .01) in the endoplasmic reticulum (ER), Golgi light fraction (GLF), and Golgi heavy fraction (GHF), respectively, and decreased this ratio by 76% ( P < .01) in carrier vesicle fraction 2 (CV2). With respect to apoE trafficking, ethanol increased rabs acylation ratio by 121% in GHF and decreased this ratio by 27% in CV2. Rabs prenylation ratio increased by 21% and 53% in GHF and CV2, respectively, and decreased by 42% in GLF. 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The in vivo 30-min incorporation ratios of [ 3H]palmitate:[ 35S]methionine or [ 3H]mevalonate:[ 35S]methionine (relative ratios of rabs acylation or prenylation to total protein or to immunoisolated apoE or transferrin) were measured in various hepatic subcellular organelles of 8 week-ethanol-fed (E) and pair-fed control (C) Wistar–Furth rats. With respect to total protein trafficking, ethanol increased rabs acylation ratio by 136% ( P < .01), 69% ( P < .05), and 64% ( P < .01) in the endoplasmic reticulum (ER), Golgi light fraction (GLF), and Golgi heavy fraction (GHF), respectively, and decreased this ratio by 76% ( P < .01) in carrier vesicle fraction 2 (CV2). With respect to apoE trafficking, ethanol increased rabs acylation ratio by 121% in GHF and decreased this ratio by 27% in CV2. Rabs prenylation ratio increased by 21% and 53% in GHF and CV2, respectively, and decreased by 42% in GLF. 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Rao, Manjunath N. ; Lakshman, M.Raj</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-b7d0a89a7525ce01422ad0be20b9d725c93e84eb8cfa932173e9673bc60f8c0c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Alcoholism</topic><topic>Alcoholism and acute alcohol poisoning</topic><topic>Animals</topic><topic>ApoE</topic><topic>Apolipoproteins E - metabolism</topic><topic>Biological and medical sciences</topic><topic>Central Nervous System Depressants - pharmacology</topic><topic>Endoplasmic Reticulum - drug effects</topic><topic>Endoplasmic Reticulum - metabolism</topic><topic>Ethanol - pharmacology</topic><topic>Golgi Apparatus - drug effects</topic><topic>Golgi Apparatus - metabolism</topic><topic>Intracellular Fluid - metabolism</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Protein trafficking</topic><topic>Protein Transport - drug effects</topic><topic>Protein Transport - physiology</topic><topic>rab GTP-Binding Proteins - physiology</topic><topic>Rabs</topic><topic>Rats</topic><topic>Rats, Inbred WF</topic><topic>Toxicology</topic><topic>Transferrin</topic><topic>Transferrin - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Marmillot, Philippe</creatorcontrib><creatorcontrib>Rao, Manjunath N.</creatorcontrib><creatorcontrib>Lakshman, M.Raj</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><jtitle>Alcohol (Fayetteville, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Marmillot, Philippe</au><au>Rao, Manjunath N.</au><au>Lakshman, M.Raj</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chronic ethanol exposure in rats affects rabs-dependent hepatic trafficking of apolipoprotein E and transferrin</atitle><jtitle>Alcohol (Fayetteville, N.Y.)</jtitle><addtitle>Alcohol</addtitle><date>2001-11-01</date><risdate>2001</risdate><volume>25</volume><issue>3</issue><spage>195</spage><epage>200</epage><pages>195-200</pages><issn>0741-8329</issn><eissn>1873-6823</eissn><coden>ALCOEX</coden><abstract><![CDATA[Because of the important roles of rabs in protein trafficking, we tested whether chronic ethanol exposure affected the trafficking of newly synthesized apolipoprotein E (apoE) or transferrin ( O-glycosylated and N-glycosylated proteins, respectively) attached to acylated or prenylated rabs. The in vivo 30-min incorporation ratios of [ 3H]palmitate:[ 35S]methionine or [ 3H]mevalonate:[ 35S]methionine (relative ratios of rabs acylation or prenylation to total protein or to immunoisolated apoE or transferrin) were measured in various hepatic subcellular organelles of 8 week-ethanol-fed (E) and pair-fed control (C) Wistar–Furth rats. With respect to total protein trafficking, ethanol increased rabs acylation ratio by 136% ( P < .01), 69% ( P < .05), and 64% ( P < .01) in the endoplasmic reticulum (ER), Golgi light fraction (GLF), and Golgi heavy fraction (GHF), respectively, and decreased this ratio by 76% ( P < .01) in carrier vesicle fraction 2 (CV2). With respect to apoE trafficking, ethanol increased rabs acylation ratio by 121% in GHF and decreased this ratio by 27% in CV2. Rabs prenylation ratio increased by 21% and 53% in GHF and CV2, respectively, and decreased by 42% in GLF. With respect to transferrin trafficking, ethanol increased rabs acylation ratio by 53% ( P < .01) in GHF, with no significant effect in ER, whereas rabs prenylation ratio increased by 26% ( P < .05) in ER, with no significant effect in GHF. Therefore, we conclude that ethanol-induced impaired trafficking of newly synthesized O- and N-glycosylated proteins occurs primarily in ER and Golgi and is due to altered lipidation of rabs, possibly rabs 1, 2, or 6 or combinations of these three rabs.]]></abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>11839466</pmid><doi>10.1016/S0741-8329(01)00179-3</doi><tpages>6</tpages></addata></record>
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subjects Alcoholism
Alcoholism and acute alcohol poisoning
Animals
ApoE
Apolipoproteins E - metabolism
Biological and medical sciences
Central Nervous System Depressants - pharmacology
Endoplasmic Reticulum - drug effects
Endoplasmic Reticulum - metabolism
Ethanol - pharmacology
Golgi Apparatus - drug effects
Golgi Apparatus - metabolism
Intracellular Fluid - metabolism
Liver - drug effects
Liver - metabolism
Male
Medical sciences
Protein trafficking
Protein Transport - drug effects
Protein Transport - physiology
rab GTP-Binding Proteins - physiology
Rabs
Rats
Rats, Inbred WF
Toxicology
Transferrin
Transferrin - metabolism
title Chronic ethanol exposure in rats affects rabs-dependent hepatic trafficking of apolipoprotein E and transferrin
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