Outbreak of diarrhoea and milk drop in cows infected with bovine group B rotavirus.
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Animals↗
Biomedical subjects
K Takeuchi
Publications and source records attributed to K Takeuchi.
Acute effects of passive smoking on the coronary circulation in healthy young adults.
CONTEXT: Recent studies have shown that passive smoking is a risk factor for ischemic heart disease and may be associated with vascular endothelial dysfunction. The acute effects of passive smoking on coronary circulation in nonsmokers are not known. OBJECTIVE: To determine the acute effects of passive smoking on coronary circulation using coronary flow velocity reserve (CFVR), assessed by noninvasive transthoracic Doppler echocardiography. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study conducted from September 2000 to November 2000 among 30 Japanese men (mean age, 27 years; 15 healthy nonsmokers and 15 asymptomatic active smokers) without history of hypertension, diabetes mellitus, or hyperlipidemia. MAIN OUTCOME MEASURES: Coronary flow velocity reserve, calculated as the ratio of hyperemic to basal coronary flow velocity induced by intravenous infusion of adenosine triphosphate and measured in each participant before and after a 30-minute exposure to environmental tobacco smoke. RESULTS: Heart rate and blood pressure responses to adenosine triphosphate infusion were not affected by passive smoking exposure in either group. Passive smoking exposure had no effect on basal coronary flow velocity in either group. Mean (SD) CFVR in nonsmokers was significantly higher than that in active smokers before passive smoking exposure (4.4 [0.91] vs 3.6 [0.88], respectively; P =.02), while CFVR after passive smoking exposure did not differ between groups (P =.83). Passive smoking exposure significantly reduced mean (SD) CFVR in nonsmokers (4.4 [0.91] vs 3.4 [0.73], respectively; P<.001). CONCLUSIONS: Passive smoking substantially reduced CFVR in healthy nonsmokers. This finding provides direct evidence that passive smoking may cause endothelial dysfunction of the coronary circulation in nonsmokers.
Adenosine Triphosphate↗
Identification of a novel human ankyrin-repeated protein homologous to CARP.
We cloned a novel ankyrin repeat protein, Arpp, by immunoscreening a cDNA library constructed from a human esophageal carcinoma cell line, TE1, with an antibody directed to a hypothetical protein encoded by antisense p53 mRNA. Arpp protein is composed of 333 amino acids and contains four ankyrin-like repeat motifs in the middle portion of the protein, a PEST-like sequence and a lysine-rich sequence similar to a nuclear localization signal in the N-terminal region, and a proline-rich region containing consensus phosphorylation sites in the C-terminal region. Protein sequence analysis revealed that Arpp is homologous (52.7% identity) to Carp which is shown to be involved in the regulation of the transcription of the cardiac ventricular myosin light chain 2 gene. Arpp mRNA was found to be expressed in normal skeletal and cardiac muscle. Interestingly, Arpp expression was detectable in bilateral ventricles, but undetectable in bilateral atria and large vessels, suggesting that Arpp may play a specific function in cardiac ventricles as well as skeletal muscles.
Ankyrin Repeat↗
Transcriptional regulation of the murine acetyl-CoA synthetase 1 gene through multiple clustered binding sites for sterol regulatory element-binding proteins and a single neighboring site for Sp1.
Cytosolic acetyl-CoA synthetase (AceCS1) activates acetate to supply the cells with acetyl-CoA for lipid synthesis. The cDNA for the mammalian AceCS1 has been isolated recently, and the mRNA was shown to be negatively regulated by sterols in cultured cells. In the current study, we describe the molecular mechanisms directing the sterol-regulated expression of murine AceCS1 by cloning and functional studies of the 5'-flanking region of the AceCS1 gene. An AceCS1 promoter-reporter gene (approximately 2.1 kilobase pairs) was negatively regulated when sterols were added to the medium of cultured cells, and the promoter was markedly induced by co-transfection of a plasmid that expresses the transcriptionally active nuclear form of either sterol regulatory element-binding protein (SREBP)-1a or -2 in HepG2 cells. Sequence analysis suggested that the AceCS1 promoter contains an E-box, two putative CCAAT-boxes, eight sterol regulatory element (SRE) motifs, and six GC-boxes. Gel shift assays demonstrated that all eight SRE motifs bound purified SREBP-1a in vitro with similar affinity. Luciferase reporter gene assays revealed that sterol regulation was critically dependent on three closely spaced SRE motifs and an adjacent GC-box. However, mutation of two putative upstream CCAAT-boxes did not affect SREBP dependent activation. Electrophoretic mobility "supershift" analyses confirmed that both Sp1 and Sp3 bound to the critical GC-box. In addition, transfection studies in Drosophila SL2 cells demonstrated that SREBP synergistically activated the AceCS1 promoter along with Sp1 or Sp3 but not with nuclear factor-Y.
Acetate-CoA Ligase↗
Cofilin phosphorylation and actin reorganization activities of testicular protein kinase 2 and its predominant expression in testicular Sertoli cells.
We previously identified testicular protein kinase 1 (TESK1), which phosphorylates cofilin and induces actin cytoskeletal reorganization. We now report identification and characterization of another member of a TESK family, testicular protein kinase 2 (TESK2), with 48% amino acid identity with TESK1. Like TESK1, TESK2 phosphorylated cofilin specifically at Ser-3 and induced formation of actin stress fibers and focal adhesions. Both TESK1 and TESK2 are highly expressed in the testis, but in contrast to TESK1, which is predominantly expressed in testicular germ cells, TESK2 is expressed predominantly in nongerminal Sertoli cells. Thus, TESK1 and TESK2 seem to play distinct roles in spermatogenesis. In HeLa cells, TESK1 was localized mainly in the cytoplasm, whereas TESK2 was localized mainly in the nucleus, which means that TESK1 and TESK2 likely have distinct cellular functions. Because the kinase-inactive mutant of TESK2 was localized in the cytoplasm, nuclear/cytoplasmic localization of TESK2 depends on its kinase activity. A TESK2 mutant lacking the C-terminal noncatalytic region had about a 10-fold higher kinase activity in vitro and, when expressed in HeLa cells, induced punctate actin aggregates in the cytoplasm and unusual condensation and fragmentation of nuclei, followed by apoptosis. Thus, we propose that the C-terminal region plays important roles in regulating the kinase activity and cellular functions of TESK2.
Actin Depolymerizing Factors↗
Paediatric brain death in Japan.
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Adolescent↗
Signaling pathways leading to transcription and translation cooperatively regulate the transient increase in expression of c-Fos protein.
The mechanisms by which growth factors trigger signal transduction pathways leading to the regulation of c-Fos expression are of great interest. In this study we investigated the effect of hepatocyte growth factor (HGF/SF) and epidermal growth factor (EGF) on the expression of c-fos and its product, c-Fos, in human epithelial cell line MKN74. The expression level of c-Fos protein in HGF/SF-stimulated cells was 5--10-fold higher than that in EGF-stimulated cells, whereas the level of c-fos mRNA induced by HGF/SF was similar to that by EGF. The hyperphosphorylation of eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), indicative of an increased number of translation initiation complexes, was detected only in HGF/SF-induced MKN74 cells. Activation of phosphatidylinositol-3'-OH kinase and FKBP12-rapamycin associated mammalian target of rapamycin (FRAP/mTOR) was observed after the treatment with HGF/SF. Pretreatment with an inhibitor of either one, i.e. LY294002 for phosphatidylinositol-3'-OH kinase or rapamycin for FRAP/mTOR, completely inhibited 4E-BP1 phosphorylation and decreased the c-Fos synthesis induced by HGF/SF down to the level found in EGF-induced cells. These results suggest that the phosphorylation of 4E-BP1 is stimulated by HGF/SF in a manner requiring both phosphatidy-linositol-3'-OH kinase-dependent and FRAP/mTOR-dependent pathways, thereby stimulating c-fos mRNA translation. Regulation of the translation process of c-fos mRNA in addition to the immediate activation of c-fos transcription is necessary for the transient increase in the level of c-Fos protein to stimulate cell proliferation.
Cell Line↗
Simple detection of severe coronary stenosis using transthoracic Doppler echocardiography at rest.
Coronary flow velocity can be measured by transthoracic Doppler echocardiography (TTDE). The purpose of this study was to detect severe coronary stenosis using the diastolic-to-systolic flow velocity ratio (DSVR) determined by TTDE at rest. We prospectively examined 190 consecutive patients with angina pectoris for whom coronary angiography was planned. Doppler spectral tracings of flow velocity in the distal left anterior descending artery were recorded by TTDE at rest. The mean and peak DSVR values were computed using mean and peak coronary flow velocities. DSVR measurement by TTDE at rest was performed within 24 hours before angiography, and in patients who underwent coronary intervention it was performed again within 48 hours after the intervention. The success rate for DSVR measurement by TTDE was 83.7%. There were significant differences in peak DSVR and mean DSVR between the patients with severe stenosis (percent diameter stenosis >85%) and those without severe stenosis (1.3 +/- 0.4 vs 1.9 +/- 0.50 and 1.2 +/- 0.4 vs 1.8 +/- 0.5, respectively; p <0.0001). In the 17 patients with successful intervention, DSVR was significantly increased after the procedure (mean 1.2 +/- 0.1 vs 2.0 +/- 0.2; peak 1.2 +/- 0.2 vs 2.0 +/- 0.3, respectively; p <0.0001). For percent diameter stenosis >85%, the best cut-off points were 1.6 for peak DSVR (sensitivity 79.0%, specificity 75.7%) and 1.5 for mean DSVR (sensitivity 77.0%, specificity 77.9%). Thus, DSVR measurement by TTDE is a simple, noninvasive method for detection of severe coronary stenosis at rest.
Adult↗
Renal tubule-specific transcription and chromosomal localization of rat thiazide-sensitive Na-Cl cotransporter gene.
The molecular mechanism underlying the renal expression localization of the thiazide-sensitive Na-Cl cotransporter (TSC) gene was studied. The TSC gene was localized to chromosome 19p12-14. In cultured cells, tissue-specific transcription activity of the 5'-flanking region of the rat rTSC gene (5'FL/rTSC) was demonstrated, and the major promoter region was located between position -580 and -141. To further examine the tissue-specific transcription, transgenic rats harboring the 5'FL/rTSC fused upstream of the LacZ gene were generated. Immunohistochemical analysis clearly showed that LacZ gene expression was co-localized to distal convoluted tubules (DCT) with TSC, indicating that the 5'FL/rTSC regulates the renal tubule-specific TSC expression. Because a transcription factor, HFH-3 (hepatocyte nuclear factor-3/folk head homologue-3), had also been localized to DCT, a possible role of the putative cis-acting element (HFH-3/rTSC, -400/-387 position) for HFH-3 binding in the tissue-specific transcription was examined. Deletion and mutation analyses suggested that transcription of the HFH-3/rTSC was actually responsive to HFH-3, and electrophoretic mobility shift assay showed a direct binding of in vitro synthesized HFH-3 to the HFH-3/rTSC. In conclusion, the rTSC gene is localized to rat chromosome 19p12--24. The transcription regulatory region of the TSC gene confers DCT-specific gene expression. DCT-specific transcription factor HFH-3 may be involved in the renal tubule-specific transcription of TSC gene.
Animals↗
Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes.
BACKGROUND: There is accumulating data that acute coronary syndromes relate to recent onset activation of inflammation affecting atherosclerotic plaques. Increased blood levels of oxidized low density lipoprotein (ox-LDL) could play a role in these circumstances. METHODS AND RESULTS: Ox-LDL levels were measured in 135 patients with acute myocardial infarction (AMI; n=45), unstable angina pectoris (UAP; n=45), and stable angina pectoris (SAP; n=45) and in 46 control subjects using a sandwich ELISA method. In addition, 33 atherectomy specimens obtained from a different cohort of patients with SAP (n=10) and UAP (n=23) were studied immunohistochemically for ox-LDL. In AMI patients, ox-LDL levels were significantly higher than in patients with UAP (P<0.0005) or SAP (P<0.0001) or in controls (P<0.0001) (AMI, 1.95+/-1.42 ng/5 microgram LDL protein; UAP, 1.19+/-0.74 ng/5 microgram LDL protein; SAP, 0.89+/-0.48 ng/5 microgram LDL protein; control, 0.58+/-0.23 ng/5 microgram LDL protein). Serum levels of total, HDL, and LDL cholesterol did not differ among these patient groups. In the atherectomy specimens, the surface area containing ox-LDL-positive macrophages was significantly higher in patients with UAP than in those with SAP (P<0.0001). CONCLUSIONS: This study demonstrates that ox-LDL levels show a significant positive correlation with the severity of acute coronary syndromes and that the more severe lesions also contain a significantly higher percentage of ox-LDL-positive macrophages. These observations suggest that increased levels of ox-LDL relate to plaque instability in human coronary atherosclerotic lesions.
Angina Pectoris↗
[Two cases of adenoid cystic carcinoma with stridor as chief complaint successfully treated with radiotherapy alone].
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Adult↗
An increase in circulating mast cell colony-forming cells in asthma.
We compared a potential to generate mast cells among various sources of CD34(+) peripheral blood (PB) cells in the presence of stem cell factor (SCF) with or without thrombopoietin (TPO), using a serum-deprived liquid culture system. From the time course of relative numbers of tryptase-positive and chymase-positive cells in the cultured cells grown by CD34(+) PB cells of nonasthmatic healthy individuals treated with G-CSF, TPO appears to potentiate the SCF-dependent growth of mast cells without influencing the differentiation into mast cell lineage. CD34(+) PB cells from asthmatic patients in a stable condition generated significantly more mast cells under stimulation with SCF alone or SCF+TPO at 6 wk of culture than did steady-state CD34(+) PB cells of normal controls. Single-cell culture studies showed a substantial difference in the number of SCF-responsive or SCF+TPO-responsive mast cell progenitors in CD34(+) PB cells between the two groups. In the presence of TPO, CD34(+) PB cells from asthmatic children could respond to a suboptimal concentration of SCF to a greater extent, compared with the values obtained by those of normal controls. Six-week cultured mast cells of asthmatic subjects had maturation properties (intracellular histamine content and tryptase/chymase enzymatic activities) similar to those derived from mobilized CD34(+) PB cells of nonasthmatic subjects. An increase in a potential of circulating hemopoietic progenitors to differentiate into mast cell lineage may contribute to the recruitment of mast cells toward sites of asthmatic mucosal inflammation.
Adolescent↗
Reactivity of anti-proliferating cell nuclear antigen (PCNA) murine monoclonal antibodies and human autoantibodies to the PCNA multiprotein complexes involved in cell proliferation.
Proliferating cell nuclear Ag (PCNA) occurs as a component of multiprotein complexes during cell proliferation. We found the complexes to react with murine anti-PCNA mAbs, but not with anti-PCNA Abs in lupus sera. The complexes were purified from rabbit thymus extract by affinity chromatography using anti-PCNA mAbs (TOB7, TO17, and TO30) and analyzed by ELISA, immunoprecipitation, immunoblotting, and HPLC gel filtration. That PCNA was complexed with other proteins was demonstrated by its copurification with a group of proteins excluded by an HPLC G3000 SW column. Although immunoblot analysis showed the mAbs to react exclusively with the 34-kDa PCNA polypeptide, they nonetheless immunoprecipitated the same group of proteins, confirming the interaction of the isolated PCNA with other proteins. Anti-PCNA sera, including AK, which reacts with biologically functional sites on PCNA, did not react with complexed PCNA, but did react with it once it was dissociated from the complexes. PCNA complexes in turn reacted with murine anti-DNA mAbs, as well as with Abs against p21, replication protein A, DNA helicase II, cyclin-dependent kinases 4 and 5, and topoisomerase I. These findings suggest that the PCNA complexes purified using anti-PCNA mAbs comprise the "protein machinery" for DNA replication and cell cycle regulation. They also suggest that anti-PCNA mAbs are useful tools with which to characterize the protein-protein interactions within PCNA complexes, as well as the autoimmune responses to proteins interacting with PCNA, which may shed light on the mechanisms of autoantibody production in lupus patients.
Animals↗
Influence of alkyl substitution on the gas-phase stability of 1-adamantyl cation and on the solvent effects in the solvolysis of 1-bromoadamantane.
1-Adamantyl cations having three methyl groups or one, two, or three isopropyl groups on the 3-, 5-, and 7-positions were found by FT ICR to be more stable than the 1-adamantyl cation and that the stability increases with the number of isopropyl group. The relative stabilities calculated by PM3 were in good agreement with the experimental results. In contrast, the sequence of the rates for the solvolysis in nonaqueous solvents are 3,5,7-(Me)(3)-1-AdBr < 1-bromoadamantane (1-AdBr) < 3,5,7-(n-Pr)(3)-1-AdBr < 3,5,7-(i-Pr)(3)-1-AdBr. The rates of solvolysis of 3,5,7-(i-Pr)(3)-1-AdBr and 3,5,7-(n-Pr)(3)-1-AdBr relative to 1-AdBr at 25 degrees C are 15 and 3.8 in EtOH, respectively, but markedly decreases with the increase in the amount of added water, reaching 0.84 and 0.15, respectively, in 60% EtOH. Reflecting these effects of water, the Grunwald-Winstein (GW) relationship for 3,5,7-(i-Pr)(3)-1-AdBr and 3,5,7-(n-Pr)(3)-1-AdBr against Y(Br) is linear for nonaqueous alcohols (EtOH, MeOH, TFE-EtOH, TFE, 97% HFIP), but marked downward deviations are observed for aqueous organic solvents, in particular, aqueous ethanol and aqueous acetone. The effect of the alkyl substituents to diminish relative solvolytic reactivity in EtOH-H(2)O mixtures may be ascribed to a blend of steric hindrance to Betarphinsted base-type hydration to the beta-hydrogens and hydrophobic interaction of the alkyl groups with ethanol to make the primary solvation shell less ionizing. The introduction of one nonyl group to the 3-position showed much smaller deviations in the GW relationship than the case of 3,5,7-(n-Pr)(3)-1-AdBr. The markedly decelerated solvolysis of alkylated 1-bromoadamantanes in aqueous organic solvents is a kinetic version of anomalously diminished dissociation of alkylbenzoic acids in aqueous ethanol and aqueous tert-butyl alcohol that was demonstrated by Wepster and co-workers a decade ago and ascribed to hydrophobic effects.
Journal Article↗
Body temperature dependency in baclofen-induced gastric acid secretion in rats relation to capsaicin-sensitive afferent neurons.
Body temperature dependency in gastric functional responses to baclofen, a GABA(B) agonist, such as acid secretion, mucosal blood flow (GMBF) and motor activity, was examined in urethane-anesthetized rats under normal (37+/-1 degrees C) and hypothermic (31+/-1 degrees C) conditions. A rat stomach was mounted in an ex-vivo chamber, perfused with saline, and the acid secretion was measured using a pH-stat method, simultaneously with GMBF by a laser Doppler flowmeter. Gastric motility was measured using a miniature balloon as intraluminal pressure recordings. Intravenous administration of baclofen significantly increased acid secretion at the doses > 0.3 mg/kg under hypothermic conditions, yet it caused a significant stimulation only at doses > 10 mg/kg under normothermic conditions. The increases in gastric motility and GMBF were similarly induced by baclofen, irrespective of whether the animals were subjected to normothermic or hypothermic conditions. These functional responses to baclofen under hypothermic conditions were totally attenuated by either bilateral vagotomy or atropine (3 mg/kg, s.c.). Baclofen at a lower dose (1 mg/kg i.v.) significantly increased the acid secretion even under normothermic conditions when the animals were subjected to chemical deafferenation of capsaicin-sensitive neurons or pretreatment with intracisternal injection of CGRP8-37 (30 ng/rat). These results suggest that 1) gastric effects of baclofen are dependent on body temperature in stimulating acid secretion but not GMBF or motor activity, 2) the acid stimulatory action of baclofen is enhanced under hypothermic conditions, and 3) the suppression of baclofen-induced acid response under normothermic conditions may be related to capsaicin-sensitive afferent neuronal activity, probably mediated by central release
Animals↗
Synthesis and characterization of ruthenium(II) molecular assemblies for photosensitization of nanocrystalline TiO2: utilization of hydroxyl grafting mode.
New Ru polypyridine complexes [(bpy)2Ru(L)]2+, where bpy = 2,2'-bipyridine and L = dipyrido[3,2-a:2',3'-c]-phenazine-2-carboxylic acid (dppzc), dipyrido[3,2-f:2',3'-h]quinoxaline-2,3-dicarboxylic acid (dpq(COOH)2), 3-hydroxydipyrido[3,2-f:2',3'-h]quinoxaline-2-carboxylic acid (dpq(OHCOOH)), 2,3-dihydroxydipyrido[3,2-f:2',3'-h]quinoxaline (dpq(OH)2), and [(L')Ru(dppzc)2]2+, where L' = bpy and 1,10-phenanthroline (phen), have been synthesized, characterized, and anchored to nanocrystalline TiO2 electrodes for light to electrical energy conversion in regenerative photoelectrochemical cells with I-/I2 acetonitrile electrolyte. These sensitizers have intense metal-to-ligand charge-transfer (MLCT) bands centered at approximately 450 nm. The effect of pH on the absorption and emission spectra of these complexes consisting of protonatable ligands has been investigated in water by spectrophotometric titration. The excited-state pKa values are more basic than the ground-state ones, except the pKa2 and pKa2* in [(bpy)2Ru(dpq(OH)2)]2+, which are equal, suggesting the localization of the lowest-energy MLCT on heteroaromatic bridging ligands, dppzc and dpq. Incident photon-to-current conversion efficiency (IPCE) is sensitive to the structural changes that resulted from introducing different functional groups, used for grafting.
Journal Article↗
Cl atom-initiated oxidation of three homologous methyl perfluoroalkyl ethers.
Chlorine atom-initiated photooxidations of three homologous methyl perfluoroalkyl ethers (HFEs), n-C(n)F(2n+1)OCH3 (n = 2, 3, and 5), in air in the absence of NOx were investigated with a long path FTIR/photochemical reaction system to elucidate the degradation mechanisms. The environmental removal processes of these three ethers in the troposphere were estimated. For oxidation of the three ethers, perfluoroalkyl formates (C(n)F(2n+1)OCHO; n = 2, 3 and 5) as relatively stable intermediates were produced at unity of the production ratio, which was independent of the perfluoroalkyl length. The rate constants for the reaction of Cl atoms with C2F5OCHO, C3F7OCHO, and C5F11OCHO were (1.2 +/- 0.5) x 10(-14), (1.2 +/- 0.5) x 10(-14), and (1.8 +/- 0.7) x 10(-14) cm3 molecule(-1) s(-1), respectively. The rate constants of the reaction of Cl with produced perfluoroalkyl formates were larger than these of perfluoroalkyl ethers. The formyl group of the perfluoroalkyl formates was finally converted to carbon dioxide. The -CF2- of the perfluoroalkyl groups for the three ethers was mainly converted to COF2 through the C-C cleavage; the conversion ratios from the carbons of the perfluoroalkyl group to COF2 were 48 +/- 10, 76 +/- 10, and 60 +/- 10% for C2F5OCH3, n-C3F7OCH3, and n-C5F11OCH3, respectively. Sixteen percent of the perfluoroalkyl group for n-C3F7OCH3 was converted to C2F5COF. Similarly, the perfluoroalkyl group of n-C5F11OCH3 was converted to C(n)F(2n+1)COF (n = 2, 3, and/or 4) with the yield of 15-30%, while for C2F5OCH3, the formation of CF3COF was not confirmed. As an oxidation product of the terminal CF3- group, 20, 22, and 16% of the CF3 group for C2F5OCH3, n-C3F7OCH3, and n-C5F11OCH3, respectively, were converted to CF3OOOCF3.
Biodegradation, Environmental↗
Acrolein induces activation of the epidermal growth factor receptor of human keratinocytes for cell death.
Acrolein, which is a highly reactive formaldehyde generated by lipid peroxidation, can affect skin and cause various disorders. The effect of exposure of human keratinocytes to acrolein on cell surface-oriented signal transduction into cells was examined. Incubation of human keratinocytes with a relatively low concentration (50 microM) of acrolein caused a prompt and selective induction of tyrosine phosphorylation of the epidermal growth factor receptor (EGFR) as a 180-kDa molecule during the period from 5-30 min after the start of incubation. This early event was followed by an increase in the density and number of phosphotyrosine-containing proteins during the period from 60-120 min after the start of incubation. The catalytic activity of EGFR as measured by the levels of autophorphorylation and phosphorylation of an exogenously added substrate, casein, in in vitro kinase assay, greatly increased as early as 1 min after the start of incubation and then decreased gradually 30 min later. MAP family kinases, including ERK, JNK, and p38 kinase, and the potentially downstream transcription factor c-Jun were all promoted for phosphorylation/activation during a period of 5-30 min. Selective prompt phosphorylation/activation of EGFR followed by phosphorylation of MAP family kinases and c-Jun and their blockade by a specific EGFR inhibitor, AG1478, suggested that activation of EGFR is the major, and possibly single, cell surface element for intracellular signal transduction in acrolein-treated cells. Incubation of human keratinocytes with 50 microM of acrolein induced atypical apoptosis with morphologic apoptotic features with low-grade oligonucleoside-sized DNA fragmentation. Partial inhibition of such a cytopathic effect of acrolein on human keratinocytes by preincubation with AG1478 suggests the involvement of an EGFR-mediated signal pathway for atypical apoptosis. These results provide new information on acrolein-induced cell surface-oriented signal transduction to human keratinocytes, and this information may be useful for understanding the pathogenesis of a number of skin diseases in response to environmental acrolein and acrolein-generating ultraviolet irradiation.
Acrolein↗