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PubMed1991

Altered metabolism of acetaldehyde in blood is not a specific marker of diabetic macroangiopathy.

Previous studies have demonstrated altered acetaldehyde metabolism in diabetics with macroangiopathy. Elimination of acetaldehyde in blood homogenates was studied in 20 non-diabetic survivors of myocardial infarction and 22 healthy controls. The half-life of acetaldehyde was shorter in patients, than in controls (mean values 83 and 150 minutes, respectively, p less than 0.001). Thus, the presence of diabetes is not a prerequisite for altered acetaldehyde metabolism in angiopathy patients. Elimination of acetaldehyde proved to be an enzymatic process, as the elimination was virtually abolished in the presence of chloral hydrate, an inhibitor of aldehyde dehydrogenase. In a previous study, however, results of a more specific assay of aldehyde dehydrogenase showed no correlation to the half-life of acetaldehyde. A possible explanation of the rapid acetaldehyde elimination in angiopathy patients is a low capacity of blood proteins for acetaldehyde binding.

Acetaldehyde↗
PubMed1989

Partition ratio of acetaldehyde between blood and breath after ethanol consumption.

Breath samples which were collected into Alcomille Breath Bags (Etzlinger Electronics, Geneve, Switzerland) were assessed for their acetaldehyde and ethanol levels by gas chromatography. Simultaneously, their levels in the venous blood were determined with the PCA method. A good correlation fit for acetaldehyde and ethanol levels was obtained in both blood and breath samples, respectively. The blood/breath partition ratio for acetaldehyde was 109 +/- 10 and that for ethanol was 2,300 +/- 100. The water/air, saline/air, and plasma/air partition ratios of acetaldehyde in vitro were 119, 120, and 155, respectively. Conversely, the water/air, saline/air, plasma/air, and blood/air partition ratios of ethanol were 2,160, 2,040, 1,920 and 1,720, respectively. The acetaldehyde in the bag was well preserved. In analyzing breath acetaldehyde, it is very important that only the end expiratory air is collected. Determination of acetaldehyde level with Alcomille Breath Bag is very useful to investigate alcohol metabolism, when some problems exist in the collection of blood samples and in the treatment for the analysis of blood acetaldehyde.

Acetaldehyde↗
PubMed1985

Effect of chronic ethanol or acetaldehyde on hepatic alcohol and aldehyde dehydrogenases, aminotransferases and glutamate dehydrogenase.

Ethanol or acetaldehyde orally administered (15% and 2% respectively in drinking water) to male Wistar rats for three months induced alterations in the main liver enzymes responsible for ethanol metabolism, aspartate and alanine aminotransferases and NAD glutamate dehydrogenase. Ethanol produced a significant decrease in the activity of soluble alcohol dehydrogenase, while acetaldehyde induced alterations both in soluble and mitochondrial aldehyde dehydrogenases: soluble activity was significantly higher than in the control and ethanol-treated groups, and mitochondrial activity was significantly diminished. Both soluble aspartate and alanine aminotransferases showed pronounced increases by the chronic effect of acetaldehyde, while mitochondrial activities were practically unchanged by the effect of ethanol or acetaldehyde. Mitochondrial NAD glutamate dehydrogenase showed a rise in its activity both by the effect of chronic ethanol and acetaldehyde consumption. The level of metabolites assayed in liver extracts showed marked differences between ethanol and acetaldehyde treatment which indicates that ethanol produced a remarkable increase in glutamate, aspartate and free ammonia together with marked decrease in pyruvate and 2-oxoglutarate concentrations. Acetaldehyde consumption induced a significant decrease in 2-oxoglutarate and pyruvate concentrations. These observations suggest that ethanol has an important effect on the urea cycle enzymes, while the effect of acetaldehyde contributes to the impairment of the citric acid cycle.

Acetaldehyde↗
PubMed1987

Peroxisomal dihydroxyacetone phosphate acyltransferase. Effect of acetaldehyde on the intact and solubilized activity.

The peroxisomal enzyme dihydroxyacetone phosphate (DHAP) acyltransferase shows a differential response to acetaldehyde. Employing whole peroxisomes, the enzyme displays a 130-400% stimulation of activity when assayed in the presence of 10-250 mM acetaldehyde. Following taurocholate solubilization of the enzyme the response to 0.25 M acetaldehyde is one of almost total inhibition. This inhibition of the taurocholate-solubilized enzyme is not observed at acetaldehyde concentrations below 200 mM. The stimulation of DHAP acyltransferase by acetaldehyde is solely a response of the peroxisomal enzyme as evidenced by its insensitivity to N-ethylmaleimide and 5 mM glycerol 3-phosphate. Furthermore, microsomal dihydroxyacetone phosphate acyltransferase activity is inhibited at all acetaldehyde concentrations. The activation of membrane-bound DHAP acyltransferase by acetaldehyde appears to be specific for this enzyme in comparison to several other peroxisomal and microsomal enzymes. The specificity of activation and differential response of the peroxisomal enzyme to acetaldehyde indicates that the microenvironment of the peroxisomal membrane is important for normal enzymatic function of this enzyme.

Acetaldehyde↗
PubMed1983

Aldehyde dehydrogenase-dependent acetaldehyde metabolism in periportal and pericentral regions of the perfused rat liver.

NADH fluorescence (366 leads to 450 nm) was measured with a large tipped light guide from the surface of rat liver perfused with hemoglobin-free medium without recirculation. A good correlation (r = 0.93) was found between the increase in NADH fluorescence and the rate of oxidation of infused acetaldehyde (0.1-4.0 mM). By using microlight guides placed on either periportal or pericentral areas of the liver, it was found that infusion of acetaldehyde increased NADH fluorescence first in periportal regions and then in pericentral areas. During retrograde perfusions, NADH fluorescence in pericentral areas increased before portal areas. By using the correlation between the increase in NADH fluorescence and the rate of acetaldehyde uptake established with the large light guide, rates of acetaldehyde uptake in pericentral and periportal areas were estimated from the microlight guide measurement of the periportal and pericentral NADH fluorescence increments caused by acetaldehyde infusions. Half-maximal acetaldehyde uptake was observed at about 0.8 mM in both regions. Maximal rates of acetaldehyde uptake were 212 and 197 mumol/g/hr in periportal and pericentral regions, respectively. The results indicate that rates of aldehyde dehydrogenase-dependent acetaldehyde oxidation are similar in periportal and pericentral regions of the liver lobule.

Acetaldehyde↗
PubMed1994

Influence of theophylline on both bronchoconstriction and plasma extravasation induced by acetaldehyde in guinea-pigs.

Acetaldehyde administered intravenously at various doses (20, 40 and 80 mg/kg) elicits a dose-dependent increase in intratracheal pressure (ITP) and a proportional rise in histamine blood concentration in anaesthetized guinea-pigs. Similar effects were observed in ovalbumin-sensitized guinea-pigs upon aerosol of acetaldehyde (20 mg/ml) which has been administered at the flow rate of 0.1 ml/min for 2 min. Theophylline (CAS 58-55-9) antagonized both the increase of ITP values and the rise of histamine in the blood caused by acetaldehyde given intravenously (ED50 = 5.8 mg/kg i.v.) or by aerosol (ED50 = 4.9 mg/kg i.v.). Furthermore, in animals where combined treatment with pyrilamine (2 mg/kg i.v.) and captopril (2 mg/kg i.v.) resulted in a remarkable potentiation of the bronchoconstrictor response to acetaldehyde (20 mg/kg i.v.), the administration of theophylline (5 mg/kg i.v.) or of the substance P (SP) receptor antagonist, [D-Pro4, D-Trp7.9] SP 4-11 (10 mg/kg i.v.) reduced the augmented action of acetaldehyde on respiratory airways induced by captopril by more than 50%. Moreover, the bronchoconstriction induced by acetaldehyde (40 mg/kg i.v.) was also associated with a significant increase of extravasation of Evans blue in tracheal tissue. Both these effects of acetaldehyde were inhibited by theophylline (10 mg/kg i.v.), whereas a NK1-TK (neurokinin 1-tachykinin) receptor antagonist (412 micrograms/kg i.v.) reduced (81%; p < 0.001) only the vascular permeability changes caused by acetaldehyde.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗
PubMed1993

Human blood acetaldehyde (update 1992).

Previously, it has been concluded that no detectable, adequately determined, acetaldehyde is to be found in the venous blood of normal Caucasian subjects during acute ethanol intake (Eriksson, 1983). Nevertheless, since then a number of reports on human blood acetaldehyde concentrations have been published. Most, if not all, of these levels can, however, be explained as being the result of artefactual sources. Thus, the early conclusion still holds, according to which the concentration of "free" and/or "loosely bound" acetaldehyde is below detection (< 0.5 microM), during normal conditions, i.e., with no deficiency in, or inhibition of, aldehyde dehydrogenase activity. Even if "free" and/or "loosely bound" acetaldehyde cannot be detected, the question of "more firmly bound" acetaldehyde has still remained open, and a number of papers have been published during the last few years on this aspect. Unfortunately, these investigations also have been seriously hampered by artefactual acetaldehyde formations during different hemolysation, hydrolysation, heating and/or other analytical procedures. The appropriate determination of bound acetaldehyde should in the future be better controlled for artefactual formations, even at very low ethanol concentrations (< 0.1 mM). Even if most of the artefactual formation is ethanol-derived, other sources for formation should also be considered. With a view to the present criteria, there is yet no valid demonstration of released acetaldehyde in human venous blood before, during, or after, normal ethanol intoxication.

Acetaldehyde↗
PubMed1994

The in vitro binding of acetaldehyde to collagen studied by neutron diffraction.

The location of acetaldehyde binding sites in the axial unit cell of tendon collagen was investigated by neutron diffraction. Acetaldehyde forms spontaneous cross-links with specific residues in collagen. The use of deuterated acetaldehyde increased the neutron scattering length of these groups. The introduction of deuterated acetaldehyde at specific locations allowed the acetaldehyde-reacted collagen to be treated as multiple isomorphous derivatives for neutron fibre diffraction. The low resolution axially projected structure was determined using amplitudes of the first eight meridional reflections (d = 67 nm). Results indicate that the process of acetaldehyde labelling takes place at different rates at different sites within the collagen fibril. The position of acetaldehyde attachment correlates well with the position of lysine and hydroxylysine residues especially in the regions of the molecular termini. This information is relevant to the process of cirrhosis and fibrosis of the liver since adduction of collagen by acetaldehyde may interfere with normal Schiff base cross-link formation at the C- and N-termini. This may result in subsequent alterations in the intra- and inter-molecular cross-linking pattern of collagen molecules.

Acetaldehyde↗
PubMed1994

Evidence for the formation of multiple types of acetaldehyde-haemoglobin adducts.

Acetaldehyde readily reacted with red blood cells and isolated haemoglobin to form adducts. We examined acetaldehyde-haemoglobin reaction products, isolated from red blood cells incubated with acetaldehyde (AcH), for the presence of stable peptide-specific acetaldehyde adducts. Red blood cell incubations were with 20, 50, and 200 mM acetaldehyde for 3, 24 and 48 hr. Peptide-specific [14C]acetaldehyde modifications of Hb from each incubation were identified by tryptic peptide mapping procedures. Nine peptides had modifications and six were found in incubations with 20 mM acetaldehyde. Two of the peptides were acetaldehyde modifications of the Hb alpha- and beta-chain N-termini. Stability studies indicated that the remaining seven [14C]AcH-modified peptides did not result, as can occur under certain conditions, from the transfer of AcH on the N-termini of Hb to N-termini formed after trypsin digestion. An analysis of the relative amounts of [14C]AcH-peptide adducts indicated that at least two of the seven peptides had reactivities for AcH different than the N-termini of Hb; that is, at least two modified peptides differ from imidazolidine-type adducts formed on the N-termini. The presence of multiple modifications with different sensitivities for AcH adduct formation may be useful in developing markers of alcohol consumption.

Acetaldehyde↗
PubMed1995

Analysis of ethanol and acetaldehyde recovery from perchloric acid-treated blood.

Recovery of acetaldehyde (0-20 microM) or ethanol (0-50 mM) added to blood and subsequently treated with perchloric acid (PCA) was evaluated using head-space gas chromatography and compared with controls. Using blood from five dogs, < 100% of acetaldehyde and ethanol was recovered from PCA-treated samples. Mathematical models of putative binding mechanisms indicated acetaldehyde partitioned simply between supernatant and PCA-induced precipitate and occupied < 1% of acetaldehyde binding sites on precipitate; ethanol partitioned simply between supernatant and precipitate and occupied > 62% of ethanol binding sites. The mathematical model also indicated acetaldehyde binding is 2500-fold stronger than ethanol binding. These results indicate as much as 46.4% of acetaldehyde may be bound to PCA-induced precipitate formed in whole blood. This loss of acetaldehyde is 3- to 4-fold greater than acetaldehyde loss caused by evaporation from PCA-treated blood.

Acetaldehyde↗
PubMed1994

The separation of hemoglobin-acetaldehyde adducts by cation exchange chromatography: a brief history.

Screening for alcohol abuse in its early phase, and the diagnosis of alcohol-related organ damage by laboratory tests in clinical settings, have often been unreliable. Protein-acetaldehyde adducts may be helpful in trying to solve this problem and hemoglobin, with its acetaldehyde adducts, appears to be a suitable model for studying protein-acetaldehyde adducts as condensation products of acetaldehyde, a harmful metabolite of ethanol. The modification by acetaldehyde alters the chromatographic properties of the hemoglobin molecule, producing a modified form that can be separated from other hemoglobin forms by cation exchange chromatographic techniques. The methods for the separation of hemoglobin acetaldehyde adducts have been improved in recent years, allowing us today to detect in vitro changes in hemoglobin caused by "physiological" concentrations of acetaldehyde and raising the possibility of developing a method suitable for clinical detection of hemoglobin acetaldehyde adducts.

Acetaldehyde↗
PubMed1997

Peptide leukotrienes mediate acetaldehyde-induced bronchial hyper-responsiveness in guinea-pigs.

BACKGROUND: We previously reported that inhaled acetaldehyde, a metabolite of ethanol and a main factor in alcohol-induced asthma, causes bronchial hyper-responsiveness (BHR) in asthmatics. However, the mechanisms are unclear. OBJECTIVE: The purpose of this study was to investigate a role of a peptide leukotriene (LT) in acetaldehyde-induced BHR. METHODS: Effects of LT antagonists, ONO-1078 (0.1-1.0 mg/kg) and ICI-198, 615 (0.03-0.3 mg/kg), on acetaldehyde-induced bronchoconstriction and BHR to inhaled methacholine were examined using a modified Konzett-Rössler method in guinea pigs. RESULTS: Acetaldehyde at 0.8 mg/ml, which failed to induce significant changes in Pao (pressure at the airway opening), enhanced an increase in Pao induced by subsequent inhalations of ascending doses (50-200 micrograms/ml) of methacholine, suggesting a potentiating effect of acetaldehyde on bronchial responsiveness. Although ONO-1078 had no inhibitory effect on bronchoconstriction caused by ascending doses (5.0-20 mg/ml) of acetaldehyde, ONO-1078 and ICI-198, 615 reduced the acetaldehyde-induced BHR. CONCLUSION: Acetaldehyde causes BHR via LT release in guinea-pigs.

Acetaldehyde↗
PubMed1997

Collagen synthesis by liver stellate cells is released from its normal feedback regulation by acetaldehyde-induced modification of the carboxyl-terminal propeptide of procollagen.

Acetaldehyde stimulates collagen synthesis in stellate cells and forms adducts with procollagen in the liver of alcoholics. To assess the possibility that modification of the carboxyl-terminal propeptide by acetaldehyde affects its capacity to exert a feedback inhibition of collagen synthesis after splitting from procollagen, the propeptide was prepared by gel filtration of the bacterial collagenase digests of procollagen type I (obtained from 10(9) calvaria fibroblasts of newborn rats) and reacted with either 250 mM acetaldehyde and 100 mM CNBH3 or with 170 microM acetaldehyde without reducing agents, to mimick in vivo conditions. The unmodified propeptide produced a concentration-dependent inhibition of collagen synthesis by Ito cells. By contrast, the acetaldehyde-modified propeptide produced a lesser inhibition of procollagen synthesis in the cells, associated with a greater accumulation of collagen in the media. The incubation with 170 microM acetaldehyde and, to a lesser extent, 50 mM ethanol produced collagenase-digestible adducts in stellate cells. Thus, the formation of acetaldehyde adducts with the carboxyl-terminal propeptide of procollagen may account, at least in part, for the stimulatory effect of acetaldehyde on collagen synthesis by stellate cells and may lead to collagen accumulation through a decrease of the normal feedback regulation of collagen synthesis by the propeptide.

Acetaldehyde↗
PubMed1998

Inhibition of intracolonic acetaldehyde production and alcoholic fermentation in rats by ciprofloxacin.

Heavy drinking is associated with many gastrointestinal symptoms and diseases, such as rapid intestinal transit time, diarrhea, colon polyps, and colorectal cancer. Acetaldehyde produced from ethanol by intestinal microbes has recently been suggested to be one of the pathogenetic factors related to alcohol-associated gastrointestinal morbidity. Furthermore, acetaldehyde is absorbed from the colon into portal blood and may thus contribute to the development of alcoholic liver injury. The present study was aimed to investigate the significance of gut aerobic flora in intracolonic acetaldehyde formation. For this study, 58 male Wistar rats (aged 9 to 11 weeks) were used. Half of the rats received ciprofloxacin for four consecutive days. Control rats (n = 29) received standard chow. On the fifth day of treatment, 1.5 g/kg body weight of ethanol was administered intraperitoneally to 19 rats receiving ciprofloxacin and 19 control rats. Ten ciprofloxacin-treated and 10 control rats received equal volumes of physiological saline intraperitoneally. Two hours after the injection of ethanol or saline, the samples of colonic contents and blood were obtained. Acetaldehyde and ethanol levels of the samples were determined by headspace gas chromatography. The intracolonic acetaldehyde level 2 hr after ethanol administration was 483+/-169 microM (maximum: 2.7 mM). High intracolonic acetaldehyde after ethanol injection was significantly reduced by ciprofloxacin treatment. After ciprofloxacin, intracolonic acetaldehyde levels before and after the injection of ethanol were 25+/-4.8 and 23+/-15 microM, respectively. Ciprofloxacin treatment resulted also in significantly higher blood (p < 0.005) and intracolonic (p < 0.0001) ethanol levels than in the control animals. Furthermore, ciprofloxacin treatment totally abolished the formation of endogenous ethanol in the large intestine. This study demonstrates that alcoholic fermentation and intracoIonic acetaldehyde production can be blocked by diminishing the amount of intracolonic aerobic bacteria with ciprofloxacin. Our findings indicate that the bacteriocolonic pathway for ethanol oxidation is mediated almost exclusively by gut aerobic microbes, and this knowledge may provide new insights into the studies on the pathogenesis of alcohol-related gastrointestinal symptoms and diseases.

Acetaldehyde↗
PubMed2001

Participation of acetaldehyde dehydrogenases in ethanol and pyruvate metabolism of the yeast Saccharomyces cerevisiae.

This work was undertaken to clarify the role of acetaldehyde dehydrogenases in Saccharomyces cerevisiae metabolism during growth on respiratory substrates. Until now, there has been little agreement concerning the ability of mutants deleted in gene ALD4, encoding mitochondrial acetaldehyde dehydrogenase, to grow on ethanol. Therefore we constructed mutants in two parental strains (YPH499 and W303-1a). Some differences appeared in the growth characteristics of mutants obtained from these two parental strains. For these experiments we used ethanol, pyruvate or lactate as substrates. Mitochondria can oxidize lactate into pyruvate using an ATP synthesis-coupled pathway. The ald4Delta mutant derived from the YPH499 strain failed to grow on ethanol, but growth was possible for the ald4Delta mutant derived from the W303-1a strain. The co-disruption of ALD4 and PDA1 (encoding subunit E1alpha of pyruvate dehydrogenase) prevented the growth on pyruvate for both strains but prevented growth on lactate only in the double mutant derived from the YPH499 strain, indicating that the mutation effects are strain-dependent. To understand these differences, we measured the enzyme content of these different strains. We found the following: (a) the activity of cytosolic acetaldehyde dehydrogenase in YPH499 was relatively low compared to the W303-1a strain; (b) it was possible to restore the growth of the mutant derived from YPH499 either by addition of acetate in the media or by introduction into this mutant of a multicopy plasmid carrying the ALD6 gene encoding cytosolic acetaldehyde dehydrogenase. Therefore, the lack of growth of the mutant derived from the YPH499 strain seemed to be related to the low activity of acetaldehyde oxidation. Therefore, when cultured on ethanol, the cytosolic acetaldehyde dehydrogenase can partially compensate for the lack of mitochondrial acetaldehyde dehydrogenase only when the activity of the cytosolic enzyme is sufficient. However, when cultured on pyruvate and in the absence of pyruvate dehydrogenase, the cytosolic acetaldehyde dehydrogenase cannot compensate for the lack of the mitochondrial enzyme because the mitochondrial form produces intramitochondrial NADH and consequently ATP through oxidative phosphorylation.

Aldehyde Oxidoreductases↗
PubMed1997

A Competitive Enzyme-Linked Immunosorbent Assay to Quantify Acetaldehyde-Protein Adducts That Accumulate in Dry Seeds during Aging.

A competitive enzyme-linked immunosorbent assay (ELISA) was developed to quantify endogenous acetaldehyde-protein adducts (APAs) produced in plant seeds at low acetaldehyde concentrations without exogenous reducing agents. The key point of this technique is the use of a gelatin-acetaldehyde adduct, which is synthesized under 1 mM acetaldehyde and 10 mM NaCNBH3, to pre-coat plate wells to obtain the proper binding parameters for the quantification of APA in seed proteins. Compared with the traditional, direct ELISA method, the competitive one has higher sensitivity and less background. Using competitive ELISA, we determined the accumulation of endogenous APAs in seeds in relation to the loss of seed viability. Lettuce seeds were exposed to 2 mM gaseous acetaldehyde during storage for 30 or 45 d; the relative humidity and temperature of storage were studied independently. Viability decreased only in acetaldehyde-treated seeds, as either the temperature or the relative humidity increased. A loss in viability was accompanied by an increase in the accumulation of APA. The APA content also increased as viability decreased in five species of seeds, which were aged naturally without exposure to acetaldehyde. It is suggested that the modification of functional seed proteins with endogenously evolved acetaldehyde may be an important cause of seed aging.

Journal Article↗
PubMed2000

Microbially produced acetaldehyde from ethanol may increase the risk of colon cancer via folate deficiency.

High alcohol and low folate intake are independent risk factors for colorectal cancer. Acetaldehyde has been postulated to be a factor responsible for ethanol-associated carcinogenesis. High levels of acetaldehyde accumulate in the large intestine via the microbial oxidation of alcohol. Acetaldehyde degrades folate in vitro. Thus, it is possible that high intracolonic acetaldehyde levels break down folate in the colon. Our aim was to test the effect of high alcohol and acetaldehyde concentrations in the gut on systemic and local intestinal folate levels in rats. Twenty rats received 3 g/kg of ethanol twice a day for 2 weeks with or without concomitant ciprofloxacin administration. Twenty control rats received saline with or without ciprofloxacin. All rats were fed a diet with normal folate content. Alcohol treatment led to very high intracolonic acetaldehyde levels (387 +/- 185 microM), which were markedly decreased by concomitant ciprofloxacin treatment (21 +/- 4 microM). Erythrocyte, serum and small intestinal folate levels were unaffected by alcohol treatment. Alcohol administration decreased significantly colonic mucosal folate levels by 48%, and this effect was prevented by ciprofloxacin. We conclude that alcohol administration for 2 weeks leads to local folate deficiency of colonic mucosa in rats, most probably via the degradation of folate by the high levels of acetaldehyde microbially produced from ethanol. Our findings offer a unique explanation for the increased risk of colonic cancer associated with alcohol intake and folate deficiency.

Acetaldehyde↗
PubMed1994

Acetaldehyde activates the promoter of the mouse alpha 2(I) collagen gene.

The mechanism whereby ethanol ingestion results in hepatic fibrosis remains unknown. Acetaldehyde has been shown to increase alpha 1(I) collagen gene transcription in human fibroblasts and in rat myofibroblastlike cells (Ito cells) in culture. In this study, the effect of acetaldehyde was determined on the activation of the alpha 2(I) collagen promoter. A plasmid containing the mouse alpha 2(I) collagen promoter region (-2000 to 54), fused to the coding sequence of the reporter gene chloramphenicol acetyl transferase and similar plasmid constructs containing deletions in the collagen promoter, were transfected into NIH 3T3 fibroblasts in culture. Acetaldehyde (200 mumol/L) and transforming growth factor-beta 1 (5 ng/ml) activated the wild type promoter. The combination of acetaldehyde and transforming growth factor-beta 1 did not result in a greater effect than either alone. Acetaldehyde inhibited, whereas transforming growth factor-beta 1 did not activate, the promoter, with a -352 to -104 deletion. By contrast, acetaldehyde had no effect, whereas transforming growth factor-beta 1 resulted in a small decrease in the activity of the promoter, with a -501 to -352 deletion. This study shows that acetaldehyde and transforming growth factor-beta 1 independently activate the mouse alpha 2(I) collagen promoter and that this activation is mediated by the same proximal region of the promoter.

Acetaldehyde↗