Abstract:
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.
journal_name
Chem Biol Interactjournal_title
Chemico-biological interactionsauthors
Smathers RL,Galligan JJ,Stewart BJ,Petersen DRdoi
10.1016/j.cbi.2011.02.021subject
Has Abstractpub_date
2011-06-30 00:00:00pages
107-12issue
1-2eissn
0009-2797issn
1872-7786pii
S0009-2797(11)00097-4journal_volume
192pub_type
杂志文章,评审abstract::The combined quantum mechanical-molecular mechanical (QM/MM) based computational scheme for modeling the structure-reaction rate correlations was elaborated for the hydrolysis of the set of neutral esters in the active site of acetylcholinesterase (AChE). The energy barriers of hydrolysis were estimated on the basis o...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2010.04.005
更新日期:2010-09-06 00:00:00
abstract::Chrysotile asbestos permeabilizes the plasma membrane of rabbit polymorphonuclear leukocytes (PMNs) which is evident from the release of the cytoplasmic enzyme lactate dehydrogenase (LDH) from the cell. When Ca2+ is present in the medium exocytosis is observed, evident from the release of the granule associated enzyme...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(89)90029-x
更新日期:1989-01-01 00:00:00
abstract::It has been suggested that the binding of iron(III) by phosvitin involves the phosphoric radicals of phosphorylserine residues, many of which are arranged in rows of several consecutive phosphoamino acids. In this paper we present evident that, unlike free phosphorylserine which does not interact with Fe(III), polypho...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(76)90161-7
更新日期:1976-10-02 00:00:00
abstract::The distribution of 203Hg after inhalation of radioactive metallic mercury (4.3 mumol 203Hg0/kg body wt. for 1 h) was studied in saline (control) and selenite (10 mumol/kg body wt. intraperitoneally, i.p.) pretreated male C57BL mice by means of whole-body autoradiography and scintillation counting. Selenite pretreatme...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(83)90014-5
更新日期:1983-09-15 00:00:00
abstract::To evaluate the protective role of cell glutathione (GSH) against the toxicity of cadmium, the effect of GSH depletion on the metal toxicity was investigated and the role of glutathione was compared with that of zinc-induced metallothioneins (MTs). A 6-h incubation of cultured Chinese hamster V79 cells with 0.2 mM L-b...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(88)90026-9
更新日期:1988-01-01 00:00:00
abstract::As part of our continuing search for bioactive natural products from plants, the present study was carried out in order to evaluate the gastroprotective properties of alkaloid extract and 2-phenylquinoline obtained from the bark of Galipea longiflora (Rutaceae). Anti-ulcer assays were performed using the following pro...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2009.04.001
更新日期:2009-07-15 00:00:00
abstract::Excessive osteoclast leads to the imbalance in bone reconstruction and results in osteolytic diseases, such as osteoporosis and rheumatic arthritis. Integrin αvβ3 abundantly expresses on osteoclast and plays a critical role in the formation and function of osteoclast, therefore, blockage of αvβ3 has become an attracti...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2020.109179
更新日期:2020-08-25 00:00:00
abstract::Butyrylcholinesterase (BChE, EC 3.1.1.8) is important in human cocaine metabolism despite its limited ability to hydrolyze this drug. Efforts to improve the catalytic efficiency of this enzyme have led to a quadruple mutant cocaine hydrolase, "CocH", that in animal models of addiction appears promising for treatment o...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2008.04.024
更新日期:2008-09-25 00:00:00
abstract::Benzo[a]pyrene (BaP) undergoes metabolic transformation in mammals via oxidative, hydrolytic, and conjugative processes; however, little is known concerning BaP conjugation in freshwater algae. It has been shown in this laboratory that BaP is metabolized by Selenastrum capricornutum via a dioxygenase pathway. This stu...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(90)90061-q
更新日期:1990-01-01 00:00:00
abstract::The effects of three fatty acids on cytotoxic aggregate formation of Ca(2+)-depleted bovine alpha-lactalbumin (apo-BLA) have been studied by UV absorbance spectroscopy and transmission electron microscopy. The experimental results demonstrate that two unsaturated fatty acids, oleic acid and linoleic acid, and one satu...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2009.03.019
更新日期:2009-07-15 00:00:00
abstract::Treatment of animals with hydrazine causes the accumulation of triglycerides in the liver but the mechanism remains unclear. Therefore, the effect of hydrazine on hepatic triglyceride synthesis and subsequent transport was studied in a hepatocyte model, in vitro in order to isolate liver cells from extrahepatic influe...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/s0009-2797(97)00090-2
更新日期:1997-11-28 00:00:00
abstract::Cisplatin induces acute renal failure in humans and mice.Tubular apoptosis, necrosis and inflammation are the primary pathogenesis of cisplatin-induced acute kidney injury(AKI). We previously reported that the depletion of Numb from proximal tubules exacerbates tubular cells apoptosis in cisplatin-induced AKI, however...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2020.109251
更新日期:2020-10-01 00:00:00
abstract::An essential oil from a lemon grass variety of Cymbopogon flexuosus (CFO) and its major chemical constituent sesquiterpene isointermedeol (ISO) were investigated for their ability to induce apoptosis in human leukaemia HL-60 cells because dysregulation of apoptosis is the hallmark of cancer cells. CFO and ISO inhibite...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2007.10.003
更新日期:2008-02-15 00:00:00
abstract::To determine correlations between the biological action pattern and chemical reactivity of alkylating agents, the rate constants for reactions of 1,3-propane sultone and 1,4-butane sultone with a series of nucleophiles at 37 degrees C have been determined. Previously published data on the mutagenicity of the two sulto...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(76)90036-3
更新日期:1976-07-01 00:00:00
abstract::The in vivo metabolite patterns of 2,5-difluoroaminobenzene and of its nitrobenzene analogue, 2,5-difluoronitrobenzene, were determined using 19F NMR analysis of urine samples. Results obtained demonstrate significant differences between the biotransformation patterns of these two analogues. For the aminobenzene, cyto...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(94)03317-2
更新日期:1995-01-01 00:00:00
abstract::Intraperitoneal administration of chloroquine, primaquine and quinacrine to rats resulted in inhibition of the hepatic microsomal mixed-function oxidases. The N-demethylation of benzphetamine (cytochrome P-450) was inhibited by chloroquine only while the O-deethylation of ethoxyresorufin (cytochrome P-448) was inhibit...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(84)90154-6
更新日期:1984-10-01 00:00:00
abstract::Colorectal cancer is the third most common cancer in the world. Cromolyn is a mast cell stabilizer and was proposed as an anticancer agent; however its high polarity limits its bioavailability by rapid washing from the body. We formulated 10 cromolyn chitosan nanoparticles (CCSNPs)1 following ionic gelation technique ...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2017.07.013
更新日期:2017-09-25 00:00:00
abstract::Fatty liver is the earliest and most common response of the liver to consumption of excessive alcohol. Steatosis can predispose the fatty liver to develop progressive liver damage. Chief among the many mechanisms involved in development of hepatic steatosis is dysregulation of insulin-mediated adipose tissue metabolis...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2020.109059
更新日期:2020-05-01 00:00:00
abstract::Epigallocatechin-3-gallate (EGCG), a tea polyphenol, inhibits the proliferation of many cancer cell lines; however, the antiproliferative mechanism(s) are not well-characterized. The objective of this study is to identify the cellular signaling mechanism(s) responsible for the antiproliferative effects of EGCG in the ...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2007.09.001
更新日期:2008-01-10 00:00:00
abstract::The present study was an attempt to investigate the hepatoprotective and antioxidative property of Phyllanthus amarus (P. amarus) extract and phyllanthin. Phyllanthin, one of the active lignin present in this plant species was isolated from the aerial parts, by silica gel column chromatography employing gradient eluti...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2009.06.014
更新日期:2009-10-30 00:00:00
abstract::The extent of DNA modification in cancerous rat live and lung tissues was investigated and compared to their respective normal tissues. Liver tumors were induced by 2-fluorenylacetamide (2-FAA) or N-nitroso-N-2-fluorenylacetamide (N-NO-2-FAA), and lung tumors were induced by sodium nitrite plus trimethylamine. In the ...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(94)03327-5
更新日期:1995-02-01 00:00:00
abstract::The pathogenesis of hepatic fibrosis involves significant deposition of fibrilar collagen and other extracellular matrix proteins. It is a rather dynamic process of wound healing in response to a variety of persistent liver injury caused by factors such as ethanol intake, viral infection, drugs, toxins, cholestasis, a...
journal_title:Chemico-biological interactions
pub_type: 杂志文章,评审
doi:10.1016/j.cbi.2011.07.001
更新日期:2011-09-30 00:00:00
abstract::It is now widely accepted that acetylcholinesterase (AChE) also displays non-cholinergic functions, completely independent of cholinergic transmission. Indeed, AChE has been implicated in a variety of trophic and toxic actions in a range of different systems. However, it is still uncertain what part of the AChE molecu...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2005.10.032
更新日期:2005-12-15 00:00:00
abstract::The present study was designed to investigate the potential therapeutic effect of trikatu, an herbal compound and its underlying molecular mechanism in rats with adjuvant-induced arthritis (AIA). Our results indicate that trikatu (1000 mg/kg/b.wt. oral) administration suppressed the production of pro-inflammatory cyto...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2016.09.003
更新日期:2016-10-25 00:00:00
abstract::Immunomodulation is a process, which alters the immune system of an organism by interfering with its functions. This interference results in either immunostimulation or immunosuppression. An immunomodulator is any substance that helps to regulate the immune system. This "regulation" is a normalization process, so that...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2008.01.008
更新日期:2008-05-28 00:00:00
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
doi:10.1016/j.cbi.2011.12.005
更新日期:2012-01-25 00:00:00
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
doi:10.1016/j.cbi.2017.11.008
更新日期:2018-01-05 00:00:00
abstract::Intracellular calcium (Ca(2+)i) overload induced by chronic hypoxia alters Ca(2+)i homeostasis, whereas ameliorating calcium homeostasis is believed to be responsible for cardioprotection. We hypothesize that cardioprotection by electromagnetic fields (EMF) exposure may restore Ca(2+)i homeostasis altered by hypoxia i...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2016.02.003
更新日期:2016-03-25 00:00:00
abstract::The combined effects of ethanol and hypoxia on the conversion of xanthine dehydrogenase (D form) to xanthine oxidase (O form) and on the leakage of the enzyme from isolated rat hepatocytes was studied. Time-dependent death of cells occurred during incubation in hypoxic conditions. Ethanol (40 mM) had only a moderate e...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(92)90093-z
更新日期:1992-06-15 00:00:00
abstract::Adverse drug reactions (ADRs) remain a major complication of drug therapy and can be classified as 'on-target' or 'off-target' (idiosyncratic) reactions. On-target reactions can be predicted from the known primary or secondary pharmacology of the drug and often represent an exaggeration of the pharmacological effect o...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2010.09.011
更新日期:2011-06-30 00:00:00