Relationship Between Drought Resistance and Betaine Aldehyde Dehydrogenase in the Shoots of Different Genotypic Wheat and Sorghum

不同基因型小麦 (TriticumaestivumL .)和高粱 (SorghumvulgareL .)的抗旱性与其种芽中的甜菜碱醛脱氢酶(BADH)的含量存在密切关系。

Role of aldehyde dehydrogenase 2 in ischemia reperfusion injury:An update

Aldehyde dehydrogenase 2(ALDH2) is best known for its critical detoxifying role in liver alcohol metabolism. However, ALDH2 dysfunction is also involved in a wide range of human pathophysiological situations and is associated with complications such as cardiovascular diseases, diabetes mellitus, neurodegenerative diseases and aging. A growing body of research has shown that ALDH2 provides important protection against oxidative stress and the subsequent loading of toxic aldehydes such as 4-hydroxy-2-nonenal and adducts that occur in human diseases, including ischemia reperfusion injury(IRI). There is increasing evidence of its role in IRI pathophysiology in organs such as heart, brain, small intestine and kidney; however, surprisingly few studies have been carried out in the liver, where ALDH2 is found in abundance. This study reviews the role of ALDH2 in modulating the pathways involved in the pathophysiology of IRI associated with oxidative stress, autophagy and apoptosis. Special emphasis is placed on the role of ALDH2 in different organs, on therapeutic "preconditioning" strategies, and on the use of ALDH2 agonists such as Alda-1, which may become a useful therapeutic tool for preventing the deleterious effects of IRI in organ transplantation.

Aldehyde dehydrogenase 2 overexpression inhibits neuronal apoptosis after spinal cord ischemia/reperfusion injury

Aldehyde dehydrogenase 2（ALDH2）is an important factor in inhibiting oxidative stress and has been shown to protect against renal ischemia/reperfusion injury.Therefore,we hypothesized that ALDH_2 could reduce spinal cord ischemia/reperfusion injury.Spinal cord ischemia/reperfusion injury was induced in rats using the modified Zivin＇s method of clamping the abdominal aorta.After successful model establishment,the agonist group was administered a daily consumption of 2.5%alcohol.At 7 days post-surgery,the Basso,Beattie,and Bresnahan score significantly increased in the agonist group compared with the spinal cord ischemia/reperfusion injury group.ALDH_2expression also significantly increased and the number of apoptotic cells significantly decreased in the agonist group than in the spinal cord ischemia/reperfusion injury group.Correlation analysis revealed that ALDH_2 expression negatively correlated with the percentage of TUNEL-positive cells（r=-0.485,P〈0.01）.In summary,increased ALDH_2 expression protected the rat spinal cord against ischemia/reperfusion injury by inhibiting apoptosis.

Genetic polymorphisms in cytochrome P4502E1, alcohol and aldehyde dehydrogenases and the risk of esophageal squamous cell carcinoma in Gansu Chinese males

AIM:To evaluate the association between genetic polymorphisms in CYP2E1, ALDH2 and ADH1B and the risk of esophageal squamous cell carcinoma (ESCC) in a high risk area of Gansu Province, in Chinese males. METHODS: A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYP2E1 *c1/*c2, ALDH2 *1/*2 and ADH1B *1/*1 genotypes). A total of 80 esophageal cancer cases and 480 controls were recruited. RESULTS: Compared with controls, cases had a greater prevalence of heavier alcohol consumption (53.8% vs 16.2%) and a higher proportion of alcohol drinkers with > 30 drink-years (28.8% vs 13.5%). Heavier alcohol consumption and alcohol drinking with > 30 drink- years increased the risk of ESCC, with ORs (95% CI) of 3.20 (1.32-9.65) and 1.68 (0.96-3.21). CYP2E1 (*c1/*c1), ALDH2 (*1/*2) and ADH1B (*1/*1) genotype frequencies were higher among patients with squamous cell carcinomas, at a level close to statistical significance (P = 0.014; P = 0.094; P = 0.0001 respectively). There were synergistic interactions among alcohol drinking and ALDH2, ADH1B and CYP2E1 genotypes. The risk of the ESCC in moderate-to-heavy drinkers with an inactive ALDH2 encoded by ALDH2 *1/*2 as well as ADH1B encoded by ADH1B *1/*1 and CYP2E1 encoded by CYP2E1 *c1/*c1 was higher than that in the never/rare-to-light drinkers with an active ALDH2 (*1/*1 genotype) as well as ADH1B (*1/*2 + *2/*2) and CYP2E1 (*c1/*c2 + *c2/*c2) genotypes, with a statistically significant difference; ORs (95% CI) of 8.58 (3.28-22.68), 27.12 (8.52-70.19) and 7.64 (2.82-11.31) respectively. The risk of the ESCC in moderate-to-heavy drinkers with ALDH2 (*1/*2) combined the ADH1B (*1/*1) genotype or ALDH2 (*1/*2) combined the CYP2E1 (*c1/*c1) genotype leads to synergistic interactions, higher than drinkers with ALDH2 (*1/*1) + ADH1B (*1/*2 + *2/*2), ALDH2 (*1/*1) + CYP2E1 (*c1/*c2 + *c2/*c2) respectively , ORs (95% CI) of 7.46 (3.28-18.32) and 6.82 (1.44-9.76) respectively. Individuals with the ADH1B combined the CYP2E1 genotype showed no synergistic interaction. CONCLUSION: In our study, we found that alcohol consumption and polymorphisms in the CYP2E1, ADH1B and ALDH2 genes are important risk factors for ESCC, and that there was a synergistic interaction among polymorphisms in the CYP2E1, ALDH2 and ADH1B genes and heavy alcohol drinking, in Chinese males living in Gansu Province, China.

Relationship between genetic polymorphisms of alcohol and aldehyde dehydrogenases and esophageal squamous cell carcinoma risk in males

AIM： To investigate the association between the genetic polymorphisms of ADH2 and ALDH2, lifetime alcohol consumption and esophageal cancer risk in the Taiwan Residents men. METHODS： Between August 2000 and June 2003, 134 pathologically-proven esophageal squamous cell carcinoma male patients and 237 male controls were recruited from Kaohsiung Medical University Hospital and Kaohsiung Veterans General Hospital in southern Taiwan. ADH2 and ALDH2 polymorphisms were genotyped using PCR-RFLP. RESULTS： Compared to those with ADH2＊2/＊2, individuals with ADH2＊1/＊2 and ADH2＊1/＊1 had 2.28- and 7.14-fold, respectively, increased risk of developing esophageal cancer （95%CI = 1.11-4.68 and 2.76-18.46） after adjusting for alcohol consumption and other covariates. The significant increased risk was also noted among subjects with ALDH2＊1/＊2 （adjusted OR （AOR） = 5.25, 95%CI = 2.47-11.19）, when compared to those with ALDH2＊1/＊1. The increased risk of esophageal cancer was made greater, when subjects carried both ADH2＊1/＊1 and ALDH2＊1/＊2, compared to those with ADH2＊1/＊2 or ADH2＊2/＊2 and ALDH2＊1/＊1 （AOR = 36.79,95%a = 9.36-144.65）. Furthhermore, we found a multipticative effect of lifetime alcoholic consumption and genotypes （ADH2 and ALDH2） on esophageal cancer risk. CONCLUSION： Our findings suggest that polymorphisms of ADH2 and ALDH2 can modify the influence of alcoholic consumption on esophageal cancer risk.

Association of genetic polymorphisms of aldehyde dehydrogenase-2 with esophageal squamous cell dysplasia

AIM:To demonstrate the possible associations between genetic polymorphisms of aldehyde dehydrogenase-2(ALDH2) and esophageal squamous cell dysplasia(ESCD).METHODS:All participants came from an area of high incidence of esophageal cancer and underwent an endoscopic staining examination;biopsies were taken from a non-staining area of the mucosa and diagnosed by histopathology.Based on the examinations,the subjects were divided into the control group with normal esophageal squamous epithelial cells and the ESCD group.ALDH2 genotypes of 396 cases were determined including 184 ESCD cases and 212 controls.The odds ratio(OR) and 95% confidence intervals(95% CI) were calculated by binary logistic regression models.RESULTS:The distribution of ALDH2 genotypes showed significant differences between the two groups.The adjustment factors were gender and age in the logistic regression models.Compared with 2*2/2*2 genotype,2*1/2*1 genotype was found to be a risk factor for ESCD,and the OR(95% CI) was 4.50(2.21-9.19).There were significant correlations between ALDH2 genotypes and alcohol drinking/smoking/history of esophageal cancer.CONCLUSION:The ALDH2 polymorphism is significantly associated with ESCD.

Transcriptional Regulation of Expression of the Maize Aldehyde Dehydrogenase 7 Gene (ZmALDH7B6) in Response to Abiotic Stresses

Aldehyde dehydrogenases（ALDHs） represent a large protein family, which includes several members that catalyze the oxidation of an aldehyde to its corresponding carboxylic acid in plants. Genes encoding members of the ALDH7 subfamily have been suggested to play important roles in various stress adaptations in plants. In this study, quantitative RT-PCR analysis revealed that a maize ALDH7 subfamily member（ZmALDH7B6） was constitutively expressed in various organs, including roots, leaves, immature ears, tassels, and developing seeds. The abundance of ZmALDH7B6 mRNA transcripts in maize roots was increased by ammonium, NaCl, and mannitol treatments. To further analyze tissue-specific and stress-induced expression patterns, the 1.5-kb 5′-flanking ZmALDH7B6 promoter region was fused to the β-glucuronidase（GUS） reporter gene and introduced into maize plants. In roots of independent transgenic lines, there was significant induction of GUS activity in response to ammonium supply, confirming ammonium-dependent expression of ZmALDH7B6 at the transcript level. Histochemical staining showed that GUS activity driven by the ZmALDH7B6 promoter was mainly localized in the vascular tissues of maize roots. These results suggested that ZmALDH7B6 is induced by multiple environmental stresses in maize roots, and may play a role in detoxifying aldehydes, particularly in vascular tissue.

Functional Characterization of an Aldehyde Dehydrogenase Homologue in Rice

The aldehyde dehydrogenase （ALDH） superfamily of NAD（P）-dependent enzymes, in general, oxidize a wide range of endogenous and exogenous aliphatic and aromatic aldehydes to their corresponding carboxylic acids and play an essential role in detoxification of reactive oxygen species （ROS） accumulated under the stressed conditions. In order to identify genes required for the stresses responses in the grass crop Oryza sativa, a homologue of ALDH gene （OsALDH22） was isolated and characterized. OsALDH22 is conserved in eukaryotes, shares high homology with the orthologs from aldehyde dehydrogenase subfamily ALDH22. The OsALDH22 encodes a protein of 597 amino acids that in plants exhibit high identity with the orthologs from Zea mays, Sorghum bicolor, Hordeum vulgare and Arabidopsis thaliana, respectively, and the conserved amino acid characteristics for ALDHs are present, including the possible NAD~ binding site （F-V-G-S- P-G-V-G）, the catalytic site （V-T-L-E-L-G-G-K） and the Cys active site. Semi-quantitative PCR and real-time PCR analysis indicates that OsALDH22 is expressed differentially in different tissues. Various elevated levels of OsALDH22 expression have been detected when the seedlings exposed to abiotic stresses including dehydration, high salinity and abscisic acid （ABA）. Transgenic rice plants overexpressing OsALDH22 show elevated stresses tolerance. On the contrary, down- 0 regulation of OsALDH22 in the RNA interference （RNAi） repression transgenic lines manifests declined stresses tolerance.

Chronic stress causes protein kinase C epsilon-aldehyde dehydrogenase 2 signaling pathway perturbation in the rat hippocampus and prefrontal cortex,but not in the myocardium

Chronic stress is strongly associated with the occurrence and development of depression and cardiovascular disease.Stress can induce altered mitochondrial function and activation of apoptosis in the cardio-cerebral system.However,it is unknown whether the protein kinase C ε（PKCε）-aldehyde dehydrogenase 2（ALDH2） pathway is altered under chronic stress,and this study sought to address this question.A rat model of depression was established using a chronic unpredictable mild stress（CUMS） protocol.After experiencing CUMS for 4 weeks,the sucrose preference test and the forced swim test verified depressive-like behaviors.Enzyme linked immunosorbent assays showed that ALDH2 activity was decreased in the rat hippocampus and prefrontal cortex,but was not altered in the myocardium.Western blot assays demonstrated reduced levels of ALDH2 and PKCε,but increased levels of 4-hydroxy-2-nonenal（4 HNE） adducts.Caspase-3 expression did not obviously alter,but active forms of caspase-3 were increased in the hippocampus and prefrontal cortex.In the myocardium,expression of ALDH2,PKCε and 4 HNE adducts did not remarkably alter;while caspase-3 expression was reduced and the active forms of caspase-3 were upregulated.Pearson＇s correlation test demonstrated that expression of 4 HNE adducts was positively correlated with levels of the active forms of caspase-3 in the hippocampus and prefrontal cortex,but not in the myocardium.In conclusion,chronic stress can damage the PKCε-ALDH2 signaling pathway in the hippocampus and prefrontal cortex,but not in the myocardium.Moreover,4 HNE is associated with active forms of caspase-3 in the hippocampus and prefrontal cortex.

Aldehyde dehydrogenase 2 preserves mitochondrial morphology and attenuates hypoxia/reoxygenationinduced cardiomyocyte injury

BACKGROUND:Disturbance of mitochondrial fi ssion and fusion(termed mitochondrial dynamics)is one of the leading causes of ischemia/reperfusion(I/R)-induced myocardial injury.Previous studies showed that mitochondrial aldehyde dehydrogenase 2(ALDH2)conferred cardioprotective effect against myocardial I/R injury and suppressed I/R-induced excessive mitophagy in cardiomyocytes.However,whether ALDH2 participates in the regulation of mitochondrial dynamics during myocardial I/R injury remains unknown.METHODS:In the present study,we investigated the effect of ALDH2 on mitochondrial dynamics and the underlying mechanisms using the H9c2 cells exposed to hypoxia/reoxygenation(H/R)as an in vitro model of myocardial I/R injury.RESULTS:Cardiomyocyte apoptosis was significantly increased after oxygen-glucose deprivation and reoxygenation(OGD/R),and ALDH2 activation largely decreased the cardiomyocyte apoptosis.Additionally,we found that both ALDH2 activation and overexpression significantly inhibited the increased mitochondrial fission after OGD/R.Furthermore,we found that ALDH2 dominantly suppressed dynamin-related protein 1(Drp1)phosphorylation(Ser616)and adenosine monophosphate-activated protein kinase(AMPK)phosphorylation(Thr172)but not interfered with the expression levels of mitochondrial shaping proteins.CONCLUSIONS:We demonstrate the protective effect of ALDH2 against cardiomyocyte H/R injury with a novel mechanism on mitochondrial fission/fusion.

Aldehyde dehydrogenase 2 suppresses cirrhosis and alcohol-induced hepatocellular carcinoma via the inhibition of acetaldehyde-derived DNA damage and multiple oncogenic signaling pathways

Objective:Hepatocellular carcinoma(HCC)is the most common primary liver cancer,the fifth most common cancer and the third most common global cause of cancer related deaths.Chronic alcohol consumption is a well-known risk factor for HCC.Acetaldehyde,a main metabolite of ethanol oxidation.

Aldehyde dehydrogenase activity helps identify a subpopulation of murine adipose-derived stem cells with enhanced adipogenic and osteogenic differentiation potential

AIMTo identify and characterize functionally distinct subpopulation of adipose-derived stem cells (ADSCs). METHODSADSCs cultured from mouse subcutaneous adipose tissue were sorted fluorescence-activated cell sorter based on aldehyde dehydrogenase (ALDH) activity, a widely used stem cell marker. Differentiation potentials were analyzed by utilizing immunocytofluorescece and its quantitative analysis. RESULTSApproximately 15% of bulk ADSCs showed high ALDH activity in flow cytometric analysis. Although significant difference was not seen in proliferation capacity, the adipogenic and osteogenic differentiation capacity was higher in ALDHHi subpopulations than in ALDHLo. Gene set enrichment analysis revealed that ribosome-related gene sets were enriched in the ALDHHi subpopulation. CONCLUSIONHigh ALDH activity is a useful marker for identifying functionally different subpopulations in murine ADSCs. Additionally, we suggested the importance of ribosome for differentiation of ADSCs by gene set enrichment analysis.

Betaine accumulation and the change of betaine-aldehyde dehydrogenase activity in barley seedlings under KCl and NaCl stress

The changes in growth status, ion contents, betaine levels and betaine\|aldehyde dehydrogenase (BADH) activity in seedlings of nonhalophyte barley treated with different concentrations of NaCl and KCl were studied. Results showed that the inhibition of growth in barley seedlings increased as enhancing NaCl and KCl for 96h and NaCl inhibitory degree was higher than that of KCl. The K\++ content of barley seedlings in NaCl was lower than the control, while the Na\++ content was higher, the levels of Na\++ fell in the seedlings treated with KCl, but K\++ levels rose, and K\++ content was higher than that of Na\++. The betaine levels of barley shoots rose with the increase in both external salt concentration and treatment time. Higher BADH activity was observed in low\|salt concentration but lower slightly in high\|salt concentration.

Expression of Acetaldehyde Dehydrogenase Gene Increases Hydrogen Production and Acetate Consumption by <i>Rhodobacter sphaeroides</i>

Rhodobacter sphaeroides RV (RV) produces high yields of hydrogen from organic acids in the presence of light. The hydrogen production from acetate is lower than that from lactate, probably because of its low ability to metabolize acetate. In this study, gene of acetaldehyde dehydrogenase (ACDH, EC 1.2.1.10) that catalyzes the reversible conversion of acetaldehyde and CoA to acetyl-CoA with the concurrent reduction of NAD to NADH, is overexpressed in the RV strain. The produced acetyl-CoA can be oxidized to carbon dioxide in the tricarboxylic acid (TCA) cycle, wherein electrons are generated and used for hydrogen production. The byproduct NADH can be used as reducing agent for acetate to produce acetaldehyde by acetate dehydrogenase. The recombinant RV strain (RVAC) expressing the ACDH gene showed ACDH activity with a specific activity of 3.2 mU/ mg, and the RV and the recombinant RV strain that harbored the intact (empty) plasmid pLP-1.2 (RVI) showed no detectable ACDH activity. The hydrogen yields of the RVAC strain from 21-mM acetate were 1.5-fold higher than that of the wild type RV strain and also that of the RVI strain. In contrast, hydrogen yield from 21-mM lactate was 30% lower than that in the control strains.

Separation and Purification of Betaine Aldehyde Dehydrogenase from Wild Suaeda liaotungensis

High active betaine aldehyde dehydrogenase (BADH, EC 1.2.1.8) is found in wild Suaeda liaotungensis . The enzyme is purified 206 fold with recovery of 1.5%. It have a specific activity of 2363 nmol/min·mg protein and the molecular mass of each subunit is 64.5 kDa as determined by SDS PAGE.

ARTP-ALE Optimized Selection of Low Acetaldehyde Producing Brewer's Yeast and Fermentation Validation

Higher levels of acetaldehyde in beer are one of the major concerns in the current beer industry.Yeast produces acetaldehyde during alcoholic fermentation,and its modification significantly affects beer flavor and quality.A different mutant strain with lower acetaldehyde production and improved ethanol tolerance was constructed using the ARTP-ALE mutagenesis strategy with 4-methylpyrazole-disulfiram.As a result of the mutation,the alcohol dehydrogenase activity of the mutant strain decreased to about 71.22%of that of the wild-type strain.At the same time,the fermentation properties and genetic stability of the newly screened strain showed slight differences from the wild-type strain,and there were no safety concerns regarding industrial use of the mutant strain.

Efficient conversion of aromatic and phenylpropanoid alcohols to acids by the cascade biocatalysis of alcohol and aldehyde dehydrogenases

Benzyl and phenylpropanoid acids are widely used in organic synthesis of fine chemicals,such as pharmaceuticals and condiments.However,biocatalysis of these acids has received less attention than chemical synthesis.One of the main challenges for biological production is the limited availability of alcohol dehydrogenases and aldehyde dehydrogenases.Environmental microorganisms are potential sources of these enzymes.In this study,129 alcohol dehydrogenases and 42 aldehyde dehydrogenases from Corynebacterium glutamicum,Pseudomonas aeruginosa,and Bacillus subtilis were identified and explored with various benzyl and phenylpropanoid alcohol and aldehyde substrates,among which four alcohol dehydrogenases and four aldehyde dehydrogenases with broad substrate specificity and high catalytic activity were obtained.Moreover,a cascade whole-cell catalytic system including ADH-90,ALDH-40,and the NAD(P)H oxidase LreNox was established,which showed high efficiency in converting cinnamyl alcohol and p-methylbenzyl alcohol into the respective carboxylic acids.Remarkably,this biocatalytic system can be easily scaled up to gram-level production,facilitating preparation purposes.

New Greener Alternative for Biocondensation of Aldehydes and Indoles Using Lemon Juice: Formation of Bis-, Tris-, and Tetraindoles

This work presents a new greener alternative for biocondensation of aldehydes and indoles for the synthesis of bis- and tris(indolyl)methanes catalyzed by lemon juice (Citrus limon) in good yields under ultrasound irradiation in aqueous ethanol. Various substituted aldehydes with indoles under this reaction condition are elucidated. Also, tetraindolyl compounds were prepared using terephthaldialdehyde by following the same protocol. This method is an environmentally benign, efficient reaction, which requires shorter reaction time and simple experimental and work-up procedures.

The effect of inactivation of aldehyde dehydrogenase on pheromone production by a gut bacterium of an invasive bark beetle,Dendroctonus valens

Semiochemical-based management strategies are important for controlling bark beetles,such as invasive Red Turpentine Beetle(Denroctonus valens),the causal agent for mass mortality of pine trees(Pinus spp.)in China.It has been previously shown that the pheromone verbenone regulates the attack density of this beetle in a dose-dependent manner and that the gut bacteria of D.valens are involved in verbenone production.However,molecular functional verification of the role of gut bacteria in the pheromone production of D.valens is still lacking.To better understand the molecular function of gut bacterial verbenone production,we chose a facultative anaerobic gut bacterium(Enterobacter xiangfangensis)of D.valens based on its strong ability to convert cis-verbenol to verbenone,as shown in our previous study,and investigated its transcriptomics in the presence or absence of cis-verbenol under anaerobic conditions(simulating the anoxic environment in the beetle's gut).Based on this transcriptome analysis,aldehyde dehydrogenase(ALDH1)was identified as a putative key gene responsible for verbenone production and was knocked-down by homologous recombination to obtain a mutant E.xiangfangensis strain.Our results show that these mutants had significantly decreased the ability to convert the monoterpene precursor to verbenone compared with the wild-type bacteria,indicating that ALDH1 is primarily responsible for verbenone conversion for this bacterium species.These findings provide further mechanistic evidence of bacterially mediated pheromone production by D.valens,add new perspective for functional studies of gut bacteria in general,and may aid the development of new gene silencing-based pest management strategies.