Overview of lipid peroxidation products and hepatic protein modification in alcoholic liver disease.


OBJECTIVES:Oxidative stress is one component of alcoholic liver disease (ALD) that is manifested in the peroxidation of cellular lipids producing the electrophile, 4-hydroxynonenal (4-HNE). This electrophile is proposed to modify essential cellular proteins resulting in loss of protein function and cellular homeostasis. Studies were initiated to identify hepatic proteins that are targets of 4-HNE modification and determine their relationship with progression of the early stages of ALD. METHODS:Rat and mouse models were developed using the Lieber-DeCarli diet to simulate early stages of ALD consisting of fatty liver (steatosis) and hepatocellular injury indicated by a 1.5-2-fold elevation of plasma ALT activity. Liver samples obtained from control and ethanol treated animals were subjected to two-dimensional electrophoresis and immunoblotting using polyclonal antibodies generated against 4-HNE epitopes for detection of proteins modified by 4-HNE. Following identification of 4-HNE adducted proteins, the respective recombinant proteins modified with physiologic concentrations of 4-HNE were evaluated to determine the functional consequences of 4-HNE modification. RESULTS:One group of proteins identified included Hsp70, Hsp90 and protein disulfide isomerase (PDI), all of which are involved in protein folding or processing are targets of adduction. In vitro assays indicated significant impairment of the protein activities following modification with physiologically relevant concentrations of 4-HNE. Liver fatty acid binding protein, L-FABP, was also identified as a target and additional studies revealed that the levels of this protein were significantly decreased because of chronic ethanol ingestion. Erk1/2 was identified as a target for modification and subsequently determined to have impaired activity. CONCLUSIONS:Inhibition of Hsp70, Hsp90 and PDI function could be involved in initiation of the early phases of ER stress contributing to stimulation and accumulation of hepatic lipids. Likewise, impairment of L-FABP activity could also disrupt lipid transport also contributing to steatosis. The modification and inhibition of Erk1/2 by 4-HNE may also contribute to the decreased hepatocellular proliferation associated with ALD. Collectively, these results provide new information concerning the mechanisms whereby the modification of hepatic proteins by 4-HNE contributes to ALD.


Chem Biol Interact


Smathers RL,Galligan JJ,Stewart BJ,Petersen DR




Has Abstract


2011-06-30 00:00:00














  • Interaction of benzo [A] pyrene and a hyperplastic agent in epidermal nuclear enlargement in the mouse. A dose response study.

    abstract::Experiments were conducted on the effects of various dose levels of benzo [a]pyrene (BP) on nuclear size in mouse interfollicular epidermis over a 3-day period. Topical application of BP was made with or without croton oil (CO) (0.1 or 0.5%) in the vehicles acetone, toluene and methyl ethyl ketone (MEK). Nuclear size ...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Ingram AJ

    更新日期:1979-06-01 00:00:00

  • Functions and distribution of NQO1 in human bone marrow: potential clues to benzene toxicity.

    abstract::NADPH:quinone oxidoreductase 1 (NQO1) may perform multiple functions within the cell. It is known to detoxify benzene-derived quinones and generate antioxidant forms of ubiquinone and Vitamin E. Recently suggested roles for NQO1 which may have relevance for mechanisms underlying benzene toxicity include modulation of ...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章,评审


    authors: Ross D

    更新日期:2005-05-30 00:00:00

  • Dichlorophenyl phosphoramidates as substrates for avian and mammalian liver phosphotriesterases: activity levels, calcium dependence and stereospecificity.

    abstract::The present study shows the existence of both Ca2+-dependent and EDTA-resistant hydrolysing activities against HDCP and paraoxon in the particulate and soluble fractions of hen, rat and rabbit liver. HDCP was more extensively hydrolysed than paraoxon in both subcellular fractions and each of three individuals of the t...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Monroy-Noyola A,Sogorb MA,Díaz-Alejo N,Níguez N,Barril J,Vicedo JL,Escudero MA,Vilanova E

    更新日期:1999-05-14 00:00:00

  • On the inhibition of microsomal drug metabolism by polychlorinated biphenyls (PCB) and related phenolic compounds.

    abstract::The in vitro metabolism of p-nitroanisole, aminopyrine, and aniline by rat liver microsomal monoxygenases were studied in the presence of different polychlorinated biphenyl (PCB) mixtures and some related hydroxybiphenyls. The tested PCB mixtures contained preferably dichloro- (di-CB), tetrachloro- (tetra-CB), or hexa...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Schmoldt A,Herzberg W,Benthe HF

    更新日期:1977-02-01 00:00:00

  • Interactions of safrole and isosafrole and their metabolites with cytochromes P-450.

    abstract::The structural features which determine interaction of safrole and related methylenedioxyphenyl compounds with cytochromes P-450 or P-448, and determine the induction of these two classes of the cytochrome, have been studied. All methylenedioxyphenyl compounds studied interact with both cytochromes P-450 and P-448 eli...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Ioannides C,Delaforge M,Parke DV

    更新日期:1985-05-01 00:00:00

  • 20(S)-protopanaxadiol (PPD) alleviates scopolamine-induced memory impairment via regulation of cholinergic and antioxidant systems, and expression of Egr-1, c-Fos and c-Jun in mice.

    abstract::20(S)-protopanaxadiol (PPD) possesses various biological properties, including anti-inflammatory, antitumor and anti-fatigue properties. Recent studies found that PPD functioned as a neurotrophic agent to ameliorate the sensory deficit caused by glutamate-induced excitotoxicity through its antioxidant effects and exhi...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Lu C,Dong L,Lv J,Wang Y,Fan B,Wang F,Liu X

    更新日期:2018-01-05 00:00:00

  • Formation of depurinating N3adenine and N7guanine adducts after reaction of 1,2-naphthoquinone or enzyme-activated 1,2-dihydroxynaphthalene with DNA. Implications for the mechanism of tumor initiation by naphthalene.

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    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Saeed M,Higginbotham S,Rogan E,Cavalieri E

    更新日期:2007-02-20 00:00:00

  • Trimetazidine protects cardiomyocytes against hypoxia-induced injury through ameliorates calcium homeostasis.

    abstract::Intracellular calcium (Ca(2+)i) overload induced by chronic hypoxia alters Ca(2+)i homeostasis, which plays an important role on mediating myocardial injury. We tested the hypothesis that treatment with trimetazidine (TMZ) would improve Ca(2+)i handling in hypoxic myocardial injury. Cardiomyocytes isolated from neonat...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Wei J,Xu H,Shi L,Tong J,Zhang J

    更新日期:2015-07-05 00:00:00

  • A marine sponge alkaloid derivative 4-chloro fascaplysin inhibits tumor growth and VEGF mediated angiogenesis by disrupting PI3K/Akt/mTOR signaling cascade.

    abstract::Tumor angiogenesis and PI3K/Akt/mTOR pathway are two major molecular objectives for the treatment and management of breast cancer. Here we first time report the molecular mechanism of a marine sponge alkaloid derivative 4-chloro fascapysin (4-CF) for its anticancer and antiangiogenesis potential. It simultaneously tar...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Sharma S,Guru SK,Manda S,Kumar A,Mintoo MJ,Prasad VD,Sharma PR,Mondhe DM,Bharate SB,Bhushan S

    更新日期:2017-09-25 00:00:00

  • Effect of riboflavin and light on the secondary structure of DNA.

    abstract::S1 nuclease hydrolysis and benzoylated naphthoylated DEAE cellulose (BND-cellulose) chromatography have been used to study the effect of riboflavin and visible light on DNA. Native calf thymus DNA was incubated with riboflavin in the presence of fluorescent light for various time periods and subjected to S1 nuclease h...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Alvi NK,Ahmad NS,Ahmad S,Hadi SM

    更新日期:1984-03-01 00:00:00

  • Partial inhibition of the P-glycoprotein-mediated transport of anthracyclines in viable resistant K562 cells after irradiation in the presence of a verapamil analogue.

    abstract::P-glycoprotein (P-gp) is a membranous ATPase responsible for the multidrug resistance phenotype. The effect on P-gp-mediated transport of anthracyclines of cell irradiation in the presence of 2,2-diphenyl-5-[N-1-(o-azidophenyl)ethylamino]valeronitrile (VP*), a photoactivable analogue of verapamil was studied in viable...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Mankhetkorn S,Teodori E,Garnier-Suillerot A

    更新日期:1999-07-01 00:00:00

  • In vitro and in vivo anticancer activity of posterior salivary gland toxin from the cuttlefish Sepia pharaonis, Ehrenberg (1831).

    abstract::Posterior salivary gland (PSG) toxins are high molecular weight toxins secreted by cephalopods and gastropods which possess immense potentials in biomedical applications. In the present study, the biomedical potentials of the PSG toxin from the cuttlefish, S. pharaonis was determined in vitro and in vivo. The cytostat...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Karthik R,Manigandan V,Ebenezar KK,Vijayashree R,Saravanan R

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  • Metabolism of benzo[a]pyrene and (-)-trans-benzo[a]pyrene-7,8-dihydrodiol by freshly isolated hepatocytes of brown bullheads.

    abstract::The metabolism of [3H]benzo[a]pyrene (BP) and (-)-trans-[14C]7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-diol) was studied in freshly isolated hepatocytes of the wild benthic fish, brown bullhead (Ictalurus nebulosus). Bullhead hepatocytes incubated with 40 microM [3H]BP for 1 h metabolized BP to water soluble met...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Steward AR,Zaleski J,Sikka HC

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  • Effect of some drugs on excision repair in E. coli cells.

    abstract::The intercalating dye ethidium bromide (EB), inhibits excision of pyrimidine dimers from UV-irradiated excision-proficient Escherichia coli B/r hcr+ cells. Inhibition is total at a 2.5 - 10(-4) M concentration 120 min after irradiation with a dose of 750 erg/mm2. The viability of irradiated cells diminishes in proport...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Masek F

    更新日期:1977-05-01 00:00:00

  • Reactive oxygen species-independent apoptosis in doxorubicin-treated H9c2 cardiomyocytes: role for heme oxygenase-1 down-modulation.

    abstract::Increased oxidative stress and apoptosis have been implicated in the cardiotoxicity that limits the clinical use of doxorubicin (DOX) as an anti-tumoral drug, but the mechanism of DOX-mediated apoptosis remains unclear. We examined the interplay between oxidative stress and cell death in cardiac-derived H9c2 myocytes ...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Bernuzzi F,Recalcati S,Alberghini A,Cairo G

    更新日期:2009-01-15 00:00:00

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    abstract::Dietary flavonoid quercetin has been suggested as a cancer chemopreventive agent, but the mechanisms of action remain unclear. This study investigated the influence of quercetin on p38-MAPK and the potential regulation of the nuclear transcription factor erythroid-2p45-related factor (Nrf2) and the cellular antioxidan...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Granado-Serrano AB,Martín MA,Bravo L,Goya L,Ramos S

    更新日期:2012-01-25 00:00:00

  • The Gillings Sampler--an electrostatic air sampler as an alternative method for aerosol in vitro exposure studies.

    abstract::There is growing interest in studying the toxicity and health risk of exposure to multi-pollutant mixtures found in ambient air, and the U.S. Environmental Protection Agency (EPA) is moving towards setting standards for these types of mixtures. Additionally, the Health Effects Institute's strategic plan aims to develo...

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    pub_type: 杂志文章


    authors: Zavala J,Lichtveld K,Ebersviller S,Carson JL,Walters GW,Jaspers I,Jeffries HE,Sexton KG,Vizuete W

    更新日期:2014-09-05 00:00:00

  • Naringenin, a flavanone inhibits the proliferation of cerebrally implanted C6 glioma cells in rats.

    abstract::Tumor cells are able to survive and proliferate in spite of their increased oxidative stress. This was taken as a hint for the implication of oxidants/antioxidants in the proliferation of glial-tumor cells. In the present study, an anti-proliferative effect of Naringenin, an antioxidant against cerebrally implanted C6...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Sabarinathan D,Mahalakshmi P,Vanisree AJ

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  • Polyproline-rich peptides associated with Torpedo californica acetylcholinesterase tetramers.

    abstract::Acetylcholinesterase (AChE) terminates cholinergic neurotransmission by hydrolyzing acetylcholine. The collagen-tailed AChE tetramer is a product of 2 genes, ACHE and ColQ. The AChE tetramer consists of 4 identical AChE subunits and one polyproline-rich peptide, whose function is to hold the 4 AChE subunits together. ...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Toker L,Silman I,Zeev-Ben-Mordehai T,Sussman JL,Schopfer LM,Lockridge O

    更新日期:2020-03-01 00:00:00

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    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Kade IJ,Balogun BD,Rocha JB

    更新日期:2013-10-25 00:00:00

  • The metabolic activation of abacavir by human liver cytosol and expressed human alcohol dehydrogenase isozymes.

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    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Walsh JS,Reese MJ,Thurmond LM

    更新日期:2002-11-10 00:00:00

  • Mechanisms underlying iron and copper ions toxicity in biological systems: Pro-oxidant activity and protein-binding effects.

    abstract::Iron and copper ions, in their unbound form, may lead to the generation of reactive oxygen species via Haber-Weiss and/or Fenton reactions. In addition, it has been shown that copper ions can irreversibly and non-specifically bind to thiol groups in proteins. This non-specific binding property has not been fully addre...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Letelier ME,Sánchez-Jofré S,Peredo-Silva L,Cortés-Troncoso J,Aracena-Parks P

    更新日期:2010-10-06 00:00:00

  • Effect of zinc, copper and glucocorticoids on metallothionein levels of cultured neurons and astrocytes from rat brain.

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    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Hidalgo J,García A,Oliva AM,Giralt M,Gasull T,González B,Milnerowicz H,Wood A,Bremner I

    更新日期:1994-12-01 00:00:00

  • The influence of p53 status on the cytotoxicity of fluorinated pyrimidine L-nucleosides.

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    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Murray V,Taylor CB,Gero AM,Lutze-Mann LH

    更新日期:2015-10-05 00:00:00

  • Evidence that covalent binding of metabolically activated phenol to microsomal proteins is caused by oxidised products of hydroquinone and catechol.

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    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Wallin H,Melin P,Schelin C,Jergil B

    更新日期:1985-11-01 00:00:00

  • The effects of baicalein on gastric mucosal ulcerations in mice: Protective pathways and anti-secretory mechanisms.

    abstract::Many flavonoids have been shown to present good results for the treatment of gastric ulcers. Baicalein, a bioactive flavonoid derived from the Scutellaria baicalensis Georgi root, possesses several biological effects, such as anti-inflammatory and antioxidant. This study was conducted to assess the gastroprotective pr...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Ribeiro AR,do Nascimento Valença JD,da Silva Santos J,Boeing T,da Silva LM,de Andrade SF,Albuquerque-Júnior RL,Thomazzi SM

    更新日期:2016-12-25 00:00:00

  • Camel milk attenuates the biochemical and morphological features of diabetic nephropathy: inhibition of Smad1 and collagen type IV synthesis.

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    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Korish AA,Abdel Gader AG,Korashy HM,Al-Drees AM,Alhaider AA,Arafah MM

    更新日期:2015-03-05 00:00:00

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    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Wang Q,Zheng J,Zou JX,Xu J,Han F,Xiang S,Liu P,Chen HW,Wang J

    更新日期:2020-02-01 00:00:00

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    journal_title:Chemico-biological interactions

    pub_type: 评论,信件


    authors: Chen A,Qin X,Tang Y,Liu M,Wang X

    更新日期:2014-10-05 00:00:00

  • Salidroside attenuates colistin-induced neurotoxicity in RSC96 Schwann cells through PI3K/Akt pathway.

    abstract::Neurotoxicity is a key dose-limiting factor for colistin therapy. This study aimed to investigate the protective effect of Salidroside on colistin-induced neurotoxicity in RSC96 Schwann cells and the underlying mechanisms. After Salidroside (12.5, 25, 50 μg/mL) treatment for 2 h, the cells were cultured with 250 μg/mL...

    journal_title:Chemico-biological interactions

    pub_type: 杂志文章


    authors: Lu Z,Jiang G,Chen Y,Wang J,Muhammad I,Zhang L,Wang R,Liu F,Li R,Qian F,Li J

    更新日期:2017-06-01 00:00:00