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Biomedical subjects

Jun Ren

Publications and source records attributed to Jun Ren.

At least 91 records · Page 5Linked to original sources
PubMed2005

The emerging role of coenzyme Q-10 in aging, neurodegeneration, cardiovascular disease, cancer and diabetes mellitus.

Coenzyme Q (ubiquinone, 2-methyl-5,6-dimethoxy-1,4-benzoquinone), soluble natural fat quinine, is crucial to optimal biological function. The coenzyme Q molecule has amphipathic (biphasic) properties due to the hydrophilic benzoquinone ring and the lipophilic poly isoprenoid side-chain. The nomenclature of coenzyme Q-n is based on the amount of isoprenoid units attached to 6-position on the benzoquinone ring. It was demonstrated that coenzyme Q, in addition to its role in electron transport and proton transfer in mitochondrial and bacterial respiration, acts in its reduced form (ubiquinol) as an antioxidant. Coenzyme Q-10 functions as a lipid antioxidant regulating membrane fluidity, recycling radical forms of vitamin C and E, and protecting membrane phospholipids against peroxidation. The antioxidant property, high degree of hydrophobicity and universal occurrence in biological system, suggest an important role for ubiquinone and ubiquinol in cellular defense against oxidative damage. Coenzyme Q-10 is a ubiquitous and endogenous lipid-soluble antioxidant found in all organisms. Neurodegenerative disorders, cancer, cardiovascular diseases and diabetes mellitus and especially aging and Alzheimer's disease exhibit altered levels of ubiquinone or ubiquinol, indicating their likely crucial role in the pathogenesis and cellular mechanisms of these ailments. This review is geared to discuss the biological effect of coenzyme Q with an emphasis on its impact in initiation, progression, treatment and prevention of neurodegenerative, cardiovascular and carcinogenic diseases.

Aging↗
PubMed2005

[Study on a monitoring program regarding leptospirosis in some fore-and-after flood-affected along large rivers in Anhui province].

OBJECTIVE: The study was designed to find out the epidemic characteristics of leptospriosis and to develop effective intervention measures. The effects of floods on leptospriosis in some areas along Yangzi river and Huai river in Anhui province was also analysed. METHODS: Study on serum epidemiology of leptospriosis was carried out from serous samples collected from native residents and animal hosts including isolation of pathogens at different phases (before,middle and after) and different monitoring spots,during the floods. RESULTS: Infection rate with leptospriosis pathogen among native residents was 13.49% during the flood-period,much higher than 2.18% at post-flood (chi2 = 22.78, P < 0.01) stage, in the flood-affected areas along Yangzi river in 1998. The average rates of infection were 2.48% and 5.35% in affected and unaffected areas along Huai river respectively, in 2003. CONCLUSIONS: There was full evidence that floods causing the epidemics of leptospriosis. However, the transmission of leptospriosis among people would depend on affecting factors as scales of floods, lasting time, coincidence between flood happening and epidemic season, immuno-protection level against leptospriosis among people and so on to a great extent. Factors as the magnitude of pathogens carried by various kinds of infectious sources were also important determinants affecting the nature, being epidemic or pandemic of leptospriosis. It was suggested that active surveillance network on the sources of infection and risk factors of leptospriosis should be developed for the control and prevention of the disease, in the flood-hit areas.

Adolescent↗
PubMed2004

Doxorubicin induces cardiomyocyte dysfunction via a p38 MAP kinase-dependent oxidative stress mechanism.

Doxorubicin, an anthracycline used for cancer therapy, is known to elicit an irreversible cardiotoxicity. Several mechanisms were postulated for its cardiac toxicity including generation of reactive oxygen species (ROS). This study was designed to determine the acute effect of doxorubicin on cardiac mechanical and intracellular Ca(2+) properties in isolated ventricular myocytes. Contractile properties of male adult rat ventricular myocytes were analyzed including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR(90)) and maximal velocity of shortening/relengthening (+/-dL/dt). Intracellular Ca(2+) transients and generation of ROS were measured with fura-2 and fluoroprobe 5-(6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate, respectively. Acute (5 min) incubation of myocytes with doxorubicin (10(-9)-10(-4)M) significantly prolonged TPS, TR(90) and intracellular Ca(2+) transient decay rate without affecting PS, +/-dL/dt, resting intracellular Ca(2+) levels and electrically triggered intracellular Ca(2+) rise. Interestingly, the doxorubicin-induced prolongation of TPS and TR(90) was ablated by treatment of the antioxidant Vitamin C (100 microM) or the p38 MAP kinase inhibitor SB203580 (10 microM). Both Vitamin C and SB203580 unmasked a doxorubicin-induced positive response in PS. Vitamin C itself enhanced basal +/-dL/dt, whereas, SB203580 unmasked a doxorubicin-induced positive response of +/-dL/dt. The doxorubicin-induced response of intracellular Ca(2+) transients was essentially unaffected by Vitamin C. The role of ROS in doxorubicin-induced cardiac contractile response was confirmed with the ability of doxorubicin to enhance ROS generation, which was prevented by Vitamin C and SB203580. These data provide evidence that doxorubicin impairs cardiac contractile property in single myocytes through an oxidative stress-mediated pathway.

Animals↗
PubMed2004

The effect of mutation on Rhodococcus equi virulence plasmid gene expression and mouse virulence.

An 81 kb virulence plasmid containing a pathogenicity island (PI) plays a crucial role in the pathogenesis of Rhodococcus equi pneumonia in foals but its specific function in virulence and regulation of plasmid-encoded virulence genes is unclear. Using a LacZ selection marker developed for R. equi in this study, in combination with an apramycin resistance gene, an efficient two-stage homologous recombination targeted gene mutation procedure was used to mutate three virulence plasmid genes, a LysR regulatory gene homologue (ORF4), a ResD-like two-component response regulator homologue (ORF8), and a gene (ORF10) of unknown function that is highly expressed by R. equi inside macrophages, as well as the chromosomal gene operon, phoPR. Virulence testing by liver clearance after intravenous injection in mice showed that the ORF4 and ORF8 mutants were fully attenuated, that the phoPR mutant was hypervirulent, and that virulence of the ORF10 mutant remained unchanged. A virulence plasmid DNA microarray was used to compare the plasmid gene expression profile of each of the four gene-targeted mutants against the parental R. equi strain. Changes were limited to PI genes and gene induction was observed for all mutants, suggesting that expression of virulence plasmid genes is dominated by a negative regulatory network. The finding of attenuation of ORF4 and ORF8 mutants despite enhanced transcription of vapA suggests that factors other than VapA are important for full expression of virulence. ORF1, a putative Lsr antigen gene, was strongly and similarly induced in all mutants, implying a common regulatory pathway affecting this gene for all four mutated genes. ORF8 is apparently the centre of this common pathway. Two distinct highly correlated gene induction patterns were observed, that of the ORF4 and ORF8 mutants, and that of the ORF10 and phoPR mutants. The gene induction pattern distinguishing these two groups paralleled their virulence in mice.

Actinomycetales Infections↗
PubMed2004

CDH1 germline mutation in hereditary gastric carcinoma.

This paper provides a bird's-eye view both in preclinical and clinical aspects of E-cadherin germline gene (CDH1) in gastric cancer patients and their families. E-cadherin, a product of CDH1 gene, belonging to the functionally related trans-membrane glycoprotein family, is responsible for the Ca(2+)-dependent cell-cell adhesion mechanism and contributes to dissociation followed by acquisition of cell motility, which usually occurs in the first step of cancer invasion and metastasis. CDH1 gene germline mutation is common in many types of carcinoma, and occurs very frequent in hereditary gastric carcinoma (HGC) patients and their families. Recently, more and more researches support that E-cadherin plays an important role in the differentiation, growth and invasion of HGC. So it is of great value to clarify its mechanisms both for understanding HGC pathogenesis and for clinical therapy, especially in China, where there are a high risk population of gastric cancer and a high HGC incidence rate. In this paper, recent researches on CDH1 gene mutation, especially its role in tumor genesis and progress of HGC, are reviewed, and advances in evaluation of its mutation status for HGC diagnosis, therapy and prognosis, are also discussed briefly.

Cadherins↗
PubMed2004

Pathological characteristics of gastric leiomyoblastoma.

AIM: To determine the pathological characteristics of gastric leiomyoblastoma. METHODS: All tissues were obtained during surgery or gastroscopy. Tissue specimens for examination by light microscope were 1 cm x 1 cm x 1 cm in size, fixed in 40 g/L neutral buffered formaldehyde, embedded in paraffin, and stained with hematoxylin and eosin. The fresh tissues obtained for electron microscopy were 1 mm x 1 mm x 1 mm in size, and fixed in phosphate buffered 30 g/L glutaraldehyde, postfixed in 10 g/L osmium tetroxide and dehydrated in graded alcohol, embebbed in Epon 812. Ultrathin sections of 50 nm were stained with uranyl acetate and lead citrate and examined under a JEM-2000 EX transmission electron microscope. RESULTS: The most important histopathological feature of leiomyoblastoma was the predominance of large, rounded or polygonal cells with characteristic perinuclear clear zone in cytoplasms. The tumor cells arranged in patch, cell junction or junctional complex could be found occasionally between cells under electron microscope. Most of the neoplastic cytoplasms were filled with myofilaments, dense bodies, and dense patches. Rough endoplasmic reticulum dilatated as lakes, and large quantities of protein secretions of intermediate electron density were found in the dilated cisternae. Intracisternal segregation could also be found. The nuclei were round or oval, and anomalous nuclei were found in part of cells. CONCLUSION: The diagnosis of gastric leiomyoblastoma can be confirmed by electron microscopy. The clear appearance of tumor cells is due to the dilation of rough endoplasmic reticulum, not fat droplets, glycogens or mucus in cytoplasm.

Actin Cytoskeleton↗
PubMed2004

Isolation and molecular characterization of the porcine stearoyl-CoA desaturase gene.

Stearoyl-CoA desaturase (SCD) is a rate-limiting enzyme in the biosynthesis of unsaturated fatty acids. So far only a partial porcine SCD sequence is available. Here we described the isolation and molecular characterization of the full-length cDNA and the determination of the genomic DNA sequence of the porcine SCD gene. The 5134-bp cDNA contains a 1080-bp open reading frame (ORF) encoding a protein of 359 amino acids with a calculated molecular mass of 41.3 kDa and a theoretical isoelectric point of 9.4. The porcine SCD protein shares high identity (>80%) with the other mammalian SCD. To further elucidate the genomic structure of the porcine SCD gene, we sequenced 20,985 bp of genomic DNA sequence encompassing the complete pig SCD gene. Similar to the other mammalian orthologs, particularly in term of exon size and exon/intron boundaries, the porcine SCD gene spans a transcription unit of 16,186 bp, consisting of six exons with sizes ranging from 131 to 4048 bp, and five introns varying in size from 518 to 4784 bp. The gene reveals a 176-bp-long 5' UTR and possesses an unusually long 3'UTR of 3848 bp in the last exon. Comparison of different mammalian SCD promoters identified some regulatory domains required for the transcription regulation in the 5' flanking sequence of the porcine SCD gene, such as the conserved polyunsaturated fatty acid response region (PUFA-RE). A total of 21 gene polymorphisms were revealed in the 21-kb DNA sequence, including 19 single nucleotide polymorphisms (SNPs), a 24-bp-long fragment length polymorphism in the fourth intron and a triplet nucleotide insertion in the fifth intron. Reverse transcription (RT)-PCR result indicates that the SCD gene is expressed ubiquitously in pigs.

5' Flanking Region↗
PubMed2004

Acetaldehyde-induced cardiac contractile dysfunction may be alleviated by vitamin B1 but not by vitamins B6 or B12.

AIMS: Chronic alcohol exposure leads to a deficiency of group B vitamins and increased risk of alcoholic cardiomyopathy characterized by impaired ventricular contractility. This study was designed to examine the effect of group B vitamin supplementation on short-term exposure of the main alcohol metabolite acetaldehyde (ACA)-induced cardiac contractile dysfunction in rat ventricular myocytes. METHODS: Mechanical contractile properties were evaluated by an IonOptix SoftEdge system. Protein damage and apoptosis were determined by protein carbonyl and caspase-3 assays, respectively. RESULTS: Short-term (4-6 h) culture of myocytes with ACA (10 microM) depressed peak shortening amplitude, maximal velocity of shortening/relengthening, shortened duration of shortening but not the duration of relengthening. ACA exposure also enhanced protein carbonyl formation and apoptosis in ventricular myocytes. The toxin-induced mechanical defects, protein damage and apoptosis were ablated by vitamin B1 (10 microM), an essential vitamin required for DNA synthesis and repair. Vitamin B6 (10 microM) attenuated ACA-induced impairment of shortening duration. Vitamin B12 (1 mM) attenuated ACA-induced reduction in maximal velocity of shortening/relengthening. Unlike vitamin B1, none of the other ACA-elicited alterations in myocyte mechanical function were affected by vitamin B6 or vitamin B12. Vitamin B6 and vitamin B12 partially, but significantly, attenuated the ACA-induced carbonyl formation without affecting ACA-induced apoptosis. CONCLUSIONS: These data provide evidence that vitamin B1 supplementation may be protective for ACA-induced cytotoxicity through protection against protein damage and apoptotic cell death in ventricular myocytes.

Acetaldehyde↗
PubMed2004

A light-driven rotaxane molecular shuttle with dual fluorescence addresses.

[reaction: see text] A molecular shuttle containing an alpha-CD macrocycle, an azobenzene unit, and two different fluorescent naphthalimide units was synthesized. The cis-trans photoisomerization of the azobenzene unit resulted in the motion of the CD macrocycle on the track. Because of the easy regulation and full reversibility of the fluorescence change of the two stopper units, the molecular shuttle could be used as a molecular storage medium or switch with all-optical inputs and outputs.

Journal Article↗
PubMed2004

Streptozotocin directly impairs cardiac contractile function in isolated ventricular myocytes via a p38 map kinase-dependent oxidative stress mechanism.

Streptozotocin (STZ) has long been used to induce experimental diabetes mellitus to study diabetic complications such as diabetic cardiomyopathy. However, direct impact of STZ on cardiac function is unknown. This study was designed to evaluate the cardiac contractile effect of STZ in isolated adult rat ventricular myocytes. Contractile properties were assessed with an IonOptix MyoCam system including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR90), and maximal velocities of shortening/relengthening (+/-dL/dt). Intracellular Ca2+ handling was evaluated with the fluorescent dye fura-2. Acute exposure of STZ (10(-9)-10(-5) M) depressed PS, prolonged TR90, and decreased electrically stimulated intracellular Ca2+ rise in a concentration-dependent manner. TPS,+/-dL/dt, resting intracellular Ca2+ level, and intracellular Ca2+ clearing rate were unaffected. The STZ-induced mechanical alterations were alleviated by the antioxidant vitamin C (100 microM) and the p38 MAP kinase inhibitor SB203580 (1 microM). 2', 7'-Dichlorofluorescein diacetate staining revealed enhanced production of reactive oxygen species following STZ treatment, which was prevented by either vitamin C or SB203580. Collectively, our data provided convincing evidence that the tool drug for experimental diabetes STZ may itself cause deleterious cardiac contractile dysfunction via an oxidative stress and p38 MAP kinase-dependent mechanism. Thus, caution should be taken when assessing diabetic heart complications using STZ-induced diabetic models.

Animals↗
PubMed2004

Disruption of the BLM gene in ATM-null DT40 cells does not exacerbate either phenotype.

Bloom syndrome and ataxia-telangiectasia are autosomal recessive human disorders characterized by immunodeficiency, genome instability and predisposition to develop cancer. Recent data reveal that the products of these two genes, BLM and ATM, interact and function together in recognizing abnormal DNA structures. To investigate the function of these two molecules in DNA damage recognition, we generated double knockouts of ATM(-/-) BLM(-/-) in the DT40 chicken B-lymphocyte cell line. The double mutant cells were viable and exhibited a variety of characteristics of both ATM(-/-) and BLM(-/-) cells. There was no evidence for exacerbation of either phenotype; however, the more extreme radiosensitivity seen in ATM(-/-) and the elevated sister chromatid exchange seen in BLM(-/-) cells were retained in the double mutants. These results suggest that ATM and BLM have largely distinct roles in recognizing different forms of damage in DNA, but are also compatible with partially overlapping functions in recognizing breaks in radiation-damaged DNA.

Adenosine Triphosphatases↗
PubMed2004

Calcium-antagonizing activity of S-petasin, a hypotensive sesquiterpene from Petasites formosanus, on inotropic and chronotropic responses in isolated rat atria and cardiac myocytes.

Petasites formosanus, an indigenous species of Petasites, has been used to treat cardiovascular diseases such as hypertension for years. We have suggested recently that S-petasin, a major sesquiterpene from P. formosanus, inhibits vascular smooth muscle contraction through inhibition of voltage-dependent Ca(2+) channels, a phenomenon possibly responsible for the hypotensive effect of P. formosanus. This study was designed to examine the chronotropic and inotropic actions of S-petasin in the heart in vivo and in vitro. Administration of S-petasin (0.1-1.5 mg/kg i.v.) in anesthetized rats reduced heart rate dose-dependently. This response was consistent with significant suppression of both contractile amplitude and spontaneous firing rate of isolated atria, responses that were not antagonized by atropine (1 microM). Mechanical evaluation in isolated ventricular myocytes showed that S-petasin (0.1 to 100 microM) depressed peak myocyte contraction and intracellular Ca(2+) transients concentration-dependently. The duration of myocyte contraction was not affected. Whole-cell voltage clamp analysis revealed that S-petasin inhibited the L-type Ca(2+) current ( I(Ca,L)) concentration-dependently and shifted the steady-state inactivation curve of I(Ca,L) to more negative potentials. However, a receptor-binding assay failed to identify any significant interaction between S-petasin (0.1-300 microM) and the dihydropyridine binding sites of L-type voltage-dependent Ca(2+) channels. Taken together, these data show that the negative chronotropic and inotropic properties of S-petasin that can be ascribed mainly to I(Ca,L) inhibition, but not to blockade of dihydropyridine binding sites of L-type Ca(2+) channel or to muscarinic receptor activation.

Animals↗
PubMed2004

Chinese literature associated with diagnosis of Helicobacter pylori.

AIM: To synthetically analyze and probe into the diagnosis of H pylori infection, we followed the principles of evidence-based medicine. METHODS: A total of 22 papers of prevalence survey and case-control studies were selected for studying about diadynamic methods. Using meta-analysis, we analyzed the different diadynamic methods of H pylori in China. RESULTS: Through meta-analysis, among the five diadynamic methods, the accuracy of polymerase chain reaction (PCR) was the highest (98.47%) and PCR was the most sensitive method (Sp: 99.03%). CONCLUSION: Among the five diadynamic methods, the accuracy of PCR is the highest and PCR is the most sensitive method to diagnose the infection of H pylori.

Asian People↗
PubMed2004

Overexpression of aldehyde dehydrogenase-2 (ALDH2) transgene prevents acetaldehyde-induced cell injury in human umbilical vein endothelial cells: role of ERK and p38 mitogen-activated protein kinase.

Acetaldehyde, the major ethanol metabolite that is far more toxic and reactive than ethanol, has been postulated to be responsible for alcohol-induced tissue and cell injury. This study was to examine whether facilitated acetaldehyde metabolism affects acetaldehyde-induced oxidative stress and apoptosis. Transgene-encoding human aldehyde dehydrogenase-2 (ALDH2), which converts acetaldehyde into acetate, was constructed under chicken beta-actin promoter and transfected into human umbilical vein endothelial cells (HUVECs). Efficacy of ALDH2 transfection was verified using green fluorescent protein and ALDH2 enzymatic assay. Generation of reactive oxygen species (ROS) was measured using chloromethyl-2',7'-dichlorodihydrofluorescein diacetate. Apoptosis was evaluated by 4',6'-diamidino-2'-phenylindoladihydrochloride fluorescence microscopy, quantitative DNA fragmentation, and caspase-3 assay. Acetaldehyde (0-200 microm) elicited ROS generation and apoptosis in HUVECs in a time- and concentration-dependent manner, associated with activation of the stress signal molecules ERK1/2 and p38 mitogen-activated protein (MAP) kinase. A close liner correlation was observed between the acetaldehyde-induced ROS generation and apoptosis. Interestingly, the acetaldehyde-induced ROS generation, apoptosis, activation of ERK1/2, and p38 MAP kinase were prevented by the ALDH2 transgene or antioxidant alpha-tocopherol. The involvement of ERK1/2 and p38 MAP kinase in acetaldehyde-induced apoptosis was confirmed by selective kinase inhibitors U0126, SB203580, and SB202190. Collectively, our data revealed that facilitation of acetaldehyde metabolism by ALDH2 transgene overexpression may prevent acetaldehyde-induced cell injury and activation of stress signals. These results indicated therapeutic potential of ALDH2 enzyme in the prevention and detoxification of acetaldehyde or alcohol-induced cell injury.

Acetaldehyde↗
PubMed2004

Action of bradykinin in the submucosal plexus of guinea pig small intestine.

Intracellular recording methods with "sharp" microelectrodes were used to study actions of bradykinin (BK) on electrical behavior of morphologically identified neurons and the identification and localization of BK receptors in the submucosal plexus of guinea pig small intestine. Exposure to BK depolarized the membrane potential and elevated excitability in submucosal neurons with AH-type electrophysiological behavior and Dogiel II multipolar morphology and in neurons with S-type electrophysiological behavior and uniaxonal morphology. BK-evoked depolarizing responses were associated with increased neuronal input resistance in AH-type neurons and decreased input resistance in S-type neurons. The selective B(2) BK receptor antagonists HOE-140 (icatabant acetate) and WIN64338 [(S)-4[2-bis(cyclohexylamino)methyleneamino]-3-(2-napthalenyl)-1-oxopropylamino]benzyl tributyl phosphonium chloride hydrochloride], but not the selective B(1) receptor antagonists des-arg(10)-HOE-140 and des-arg(9)-leu(8)-BK, suppressed the BK-evoked responses. The selective B(2) receptor agonist Kallidin, but not the selective B(1) receptor agonist des-arg(9)-BK mimicked the excitatory action of BK. Western blot analysis and reverse transcription-polymerase chain reaction confirmed the expression of B(2) receptor protein and mRNA. Binding studies with a fluorescently labeled BK(2) antagonist found expression of B(2) receptors on a majority of the ganglion cells. B(2) receptors occupied 82% of the neurons that expressed immunoreactivity for neuropeptide Y, 75% of the neurons that expressed vasoactive intestinal peptide, 84% of the neurons that expressed substance P, 71% of the neurons that expressed choline acetyltransferase, and all neurons that expressed calbindin immunoreactivity. The results suggest that the B(2) receptor mediates the excitatory action of BK on submucosal plexus neurons. Pathophysiological significance of the excitatory actions on secretomotor neurons might be stimulated mucosal secretion and the secretory diarrhea associated with intestinal inflammatory states.

Animals↗
PubMed2004

Metabotropic signal transduction for bradykinin in submucosal neurons of guinea pig small intestine.

Intracellular recording methods with "sharp" microelectrodes were used to study signal transduction mechanisms underlying the excitatory action of bradykinin (BK) in morphologically identified neurons in the small intestinal submucosal plexus. Exposure to BK evoked slowly activating membrane depolarization and enhanced excitability associated with increased input resistance in AH-type and decreased input resistance in S-type neurons. Preincubation with pertussis toxin did not affect the BK-evoked responses. Pretreatment with the cyclooxygenase inhibitors indomethacin or piroxicam suppressed or abolished the BK-evoked responses. Application of prostaglandin (PG) E(2) or PG analogs evoked BK-like depolarizing responses in the submucosal plexus with a potency order of PGE(2) > PGE(1) > 17-phenyl trinor-PGE(2) > PGI(2) > sulprostone > PGF(2alpha). Depolarizing responses to bradykinin or PGE(2) in S-type neurons were suppressed in the presence of the phospholipase C inhibitor U73122 [(1-6-[([17beta]-3-methoxyestra-1,3,5[10]-tren-17-71)amino]hexyl)-1H-pyrrole-2,5-dione)], but not the inactive analog U73343 [(1-6-[([17beta]-3-methoxyestra-1,3,5[10]trien-17yl)amino]hexyl)-2,5-pyrrolidinedione)]. The inositol-1,4,5-trisphosphate receptor antagonist 2-aminoethoxy-diphenylborane and the calmodulin inhibitor W-7, but not ryanodine, suppressed both bradykinin- and PGE(2)-evoked responses. KN-62, an inhibitor of calmodulin kinases, or GF109203X, a specific protein kinase C inhibitor, suppressed both BK- and PGE(2)-evoked depolarizing responses. Selective protein kinase A inhibitors did not alter BK- or PGE(2)-evoked depolarizing responses in S neurons. The results suggest that BK stimulates synthesis and release of PGE(2), which acts at EP(1) receptors to evoke depolarizing responses in submucosal neurons. The postreceptor transduction cascade includes activation of phospholipase C, inositol-1,4,5-trisphosphate production, intraneuronal Ca2+ mobilization, activation of protein kinase C and/or calmodulin kinases, and phosphorylation of cationic channels.

Animals↗
PubMed2004

Ethanol and acetaldehyde in alcoholic cardiomyopathy: from bad to ugly en route to oxidative stress.

Alcoholic cardiomyopathy is characterized by cardiomegaly, disruptions of myofibrillary architecture, reduced myocardial contractility, decreased ejection fraction, and enhanced risk of stroke and hypertension. Although several mechanisms have been postulated for alcoholic cardiomyopathy, including oxidative damage, accumulation of triglycerides, altered fatty acid extraction, decreased myofilament Ca(2+) sensitivity, and impaired protein synthesis, neither the mechanism nor the ultimate toxin has been unveiled. Primary candidates acting as specific toxins of myocardial tissue are ethanol; its first and major metabolic product, acetaldehyde; and fatty acid ethyl esters. Acetaldehyde has been demonstrated to impair directly cardiac contractile function, disrupt cardiac excitation-contractile coupling, and contribute to oxidative damage and lipid peroxidation. Acetaldehyde-elicited cardiac dysfunction may be mediated through cytochrome P450 oxidase, xanthine oxidase, and the stress-signaling cascade. Unfortunately, the most direct approach that can be used to examine toxicity is hampered by the fact that direct intake of acetaldehyde is highly toxic and unsuitable for long-term study. To overcome this obstacle, transgenic mice have been used to alter artificially ethanol/acetaldehyde metabolism, resulting in elevated acetaldehyde concentrations after ethanol ingestion. In this review, we summarize results obtained with the use of transgenic animal models to elucidate the role of acetaldehyde in the mechanism of action in alcoholic cardiomyopathy.

Acetaldehyde↗