Formaldehyde Stress Research Articles

Core pathways operating during methylotrophy of Bacillus methanolicus MGA3 and induction of a bacillithiol-dependent detoxification pathway upon formaldehyde stress.

Bacillus methanolicus MGA3 is a model facultative methylotroph of interest for fundamental research and biotechnological applications. Previous research uncovered a number of pathways potentially involved in one-carbon substrate utilization. Here, we applied dynamic (13) C labeling to elucidate which of these pathways operate during growth on methanol and to uncover potentially new ones. B. methanolicus MGA3 uses the assimilatory and dissimilatory ribulose monophosphate (RuMP) cycles for conversion of the central but toxic intermediate formaldehyde. Additionally, the operation of two cofactor-dependent formaldehyde oxidation pathways with distinct roles was revealed. One is dependent on tri- and tetraglutamylated tetrahydrofolate (THF) and is involved in formaldehyde oxidation during growth on methanol. A second pathway was discovered that is dependent on bacillithiol, a thiol cofactor present also in other Bacilli where it is known to function in redox-homeostasis. We show that bacillithiol-dependent formaldehyde oxidation is activated upon an upshift in formaldehyde induced by a substrate switch from mannitol to methanol. The genes and the corresponding enzymes involved in the biosynthesis of bacillithiol were identified by heterologous production of bacillithiol in Escherichia coli. The presented results indicate metabolic plasticity of the methylotroph allowing acclimation to fluctuating intracellular formaldehyde concentrations.

Contribution of Fdh3 and Glr1 to Glutathione Redox State, Stress Adaptation and Virulence in Candida albicans.

The major fungal pathogen of humans, Candida albicans, is exposed to reactive nitrogen and oxygen species following phagocytosis by host immune cells. In response to these toxins, this fungus activates potent anti-stress responses that include scavenging of reactive nitrosative and oxidative species via the glutathione system. Here we examine the differential roles of two glutathione recycling enzymes in redox homeostasis, stress adaptation and virulence in C. albicans: glutathione reductase (Glr1) and the S-nitrosoglutathione reductase (GSNOR), Fdh3. We show that the NADPH-dependent Glr1 recycles GSSG to GSH, is induced in response to oxidative stress and is required for resistance to macrophage killing. GLR1 deletion increases the sensitivity of C. albicans cells to H2O2, but not to formaldehyde or NO. In contrast, Fdh3 detoxifies GSNO to GSSG and NH3, and FDH3 inactivation delays NO adaptation and increases NO sensitivity. C. albicans fdh3⎔ cells are also sensitive to formaldehyde, suggesting that Fdh3 also contributes to formaldehyde detoxification. FDH3 is induced in response to nitrosative, oxidative and formaldehyde stress, and fdh3Δ cells are more sensitive to killing by macrophages. Both Glr1 and Fdh3 contribute to virulence in the Galleria mellonella and mouse models of systemic infection. We conclude that Glr1 and Fdh3 play differential roles during the adaptation of C. albicans cells to oxidative, nitrosative and formaldehyde stress, and hence during the colonisation of the host. Our findings emphasise the importance of the glutathione system and the maintenance of intracellular redox homeostasis in this major pathogen.

The effects of overexpression of formaldehyde dehydrogenase gene from Brevibacillus brevis on the physiological characteristics of tobacco under formaldehyde stress

The faldh gene encodes the Brevibacillus brevis glutathione-dependent formaldehyde dehydrogenase (FALDH), an enzyme involved in formaldehyde metabolism. In the present work, we have investigated the physiological characteristics of transgenic faldh tobacco under formaldehyde stress. Overexpression of B. brevis FALDH confers tobacco tolerance to high HCHO concentrations. The transgenic tobacco lines had the higher biomass, produced the higher content of total proteins and soluble sugars, the lower levels of MDA, protein carbonyl (PC), and H2O2 as compared with the wild-type tobacco under HCHO stress. The contents of chlorophyll (Chl), including Chl a, Chl b, and the ratio of Chl a/b, and the content of anthocyanidin in transgenic plants under HCHO stress were also higher than that in wild-type tobacco. These results show that high HCHO tolerance and changes of physiological characteristics related to stress tolerance were due to the overexpressing of FALDH in tobacco.

The protective effect of geniposide on human neuroblastoma cells in the presence of formaldehyde

BackgroundFormaldehyde can induce misfolding and aggregation of Tau protein and β amyloid protein, which are characteristic pathological features of Alzheimer’s disease (AD). An increase in endogenous formaldehyde concentration in the brain is closely related to dementia in aging people. Therefore, the discovery of effective drugs to counteract the adverse impact of formaldehyde on neuronal cells is beneficial for the development of appropriate treatments for age-associated cognitive decline.MethodsIn this study, we assessed the neuroprotective properties of TongLuoJiuNao (TLJN), a traditional Chinese medicine preparation, against formaldehyde stress in human neuroblastoma cells (SH-SY5Y cell line). The effect of TLJN and its main ingredients (geniposide and ginsenoside Rg1) on cell viability, apoptosis, intracellular antioxidant activity and the expression of apoptotic-related genes in the presence of formaldehyde were monitored.ResultsCell counting studies showed that in the presence of TLJN, the viability of formaldehyde-treated SH-SY5Y cells significantly recovered. Laser scanning confocal microscopy revealed that the morphology of formaldehyde-injured cells was rescued by TLJN and geniposide, an effective ingredient of TLJN. Moreover, the inhibitory effect of geniposide on formaldehyde-induced apoptosis was dose-dependent. The activity of intracellular antioxidants (superoxide dismutase and glutathione peroxidase) increased, as did mRNA and protein levels of the antiapoptotic gene Bcl-2 after the addition of geniposide. In contrast, the expression of the apoptotic-related gene - P53, apoptotic executer - caspase 3 and apoptotic initiator - caspase 9 were downregulated after geniposide treatment.ConclusionsOur results indicate that geniposide can protect SH-SY5Y cells against formaldehyde stress through modulating the expression of Bcl-2, P53, caspase 3 and caspase 9, and by increasing the activity of intracellular superoxide dismutase and glutathione peroxidase.

Formaldehyde induces hyperphosphorylation and polymerization of Tau protein both in vitro and in vivo

BackgroundChronic formaldehyde exposure leads to memory impairment and abnormal elevation of endogenous formaldehyde has been found in the brains of Alzheimer's disease (AD) patients. Hyperphosphorylated Tau protein with subsequent aggregates as neurofibrillary tangles (NFTs) is one of the typical pathological characteristics in AD brains. The mechanism underlying abnormally elevated concentrations of endogenous formaldehyde that induce Tau hyperphosphorylation is unknown. MethodsN2a cells and mice were treated with formaldehyde for different time points, then Western blotting and immunocytochemistry were utilized to determine the phosphorylation and polymerization of Tau protein. HPLC was used to detect the concentration of formaldehyde in cell media. ResultsUnder formaldehyde stress, Tau became hyperphosphorylated, not only in the cytoplasm, but also in the nucleus of neuroblastoma (N2a) cells, and mouse brains. Polymers of cellular phospho-Tau were also detected. Significant accumulation of glycogen synthase kinase-3β (GSK-3β) in the nucleus of N2a and mouse brain cells, and elevation of its phosphorylation at Y216, was observed under formaldehyde stress. Formaldehyde-induced Tau hyperphosphorylation was blocked in the presence of LiCl and CT99021, inhibitors of GSK-3β, and by RNAi interference. ConclusionsFormaldehyde, which may cause age-related memory loss, can act as a factor triggering Tau hyperphosphorylation via GSK-3β catalysis and induces polymerization of Tau. General significanceInvestigation of formaldehyde-induced Tau hyperphosphorylation may provide novel insights into mechanisms underlying tauopathies.

The Effects of Overexpression of Formaldehyde Dehydrogenase Gene fromBrevibacillus brevison the Physiological Characteristics of Tobacco under Formaldehyde Stress

The Effects of Overexpression of Formaldehyde Dehydrogenase Gene from<i>Brevibacillus brevis</i>on the Physiological Characteristics of Tobacco under Formaldehyde Stress

Effects of Formaldehyde Stress on Physiological Characteristics and Gene Expression Associated with Photosynthesis in Arabidopsis thaliana

Leaf chlorosis and bleach in plants under formaldehyde (HCHO) stress has been observed in previous studies. To better understand the mechanism of HCHO inhibition on photosynthesis, effects of HCHO stress on physiological characteristics and gene expression associated with photosynthesis in Arabidopsis thaliana were investigated in this study. The results indicated that HCHO stress reduced total chlorophyll (Chl) and Chl b content but increased Chl a content and a/b ratio in Arabidopsis. Suppression subtractive hybridization analysis identified 22 potential HCHO-repressive genes associated with photosynthesis. Furthermore, RT-PCR data showed that transcriptional levels of Lhcb2.1, Lhcb3, Lhca4, RBCS1A, RCA, Psao, Psbo, and Psbp were reduced to their lowest levels at 4 h after Arabidopsis was treated with 2–4 mM HCHO. The restoration in expression levels of Lhcb3, Lhca4, RBCS1A, and Psbp as well as up-regulation in Lhcb2.1 and RCA transcription was observed from 12 to 24 h after HCHO treatment. 13C-NMR analysis revealed that change patterns of endogenous glucose content were similar to expression patterns of these genes under HCHO stress from 0.5 to 24 h. The glucose content decreased to the lowest level at 4 h, accompanied by a potent inhibition on the capacity of CO2 assimilation caused by exogenous HCHO. From 4 to 24 h of HCHO stress, exogenous HCHO was efficiently metabolized and converted to glucose, which allowed the glucose content to be restored to its original level; thus, repressive effects of HCHO stress on expressions of photosynthesis-related genes were eliminated. These results suggested a correlation between HCHO metabolic level and expression levels of photosynthesis-related genes in vivo during this period. However, a second reduction in expressions of these genes after 36 h might be attributed to other effects triggered by HCHO stress.

枯草芽孢杆菌萌发后孢子响应甲醛胁迫过程的拉曼光谱研究

枯草芽孢杆菌萌发后孢子响应甲醛胁迫过程的拉曼光谱研究

Formaldehyde stress

Formaldehyde, one of the most toxic organic compounds, is produced and processed in human cells. The level of human endogenous formaldehyde is maintained at a low concentration (0.01-0.08 mmol L(-1) in blood) under physiological conditions, but the concentration increases during ageing (over 65 years old). Clinical trials have shown that urine formaldehyde concentrations are significantly different between elderly Alzheimer's patients (n=91) and normal elderly volunteers (n=38) (P<0.001). Abnormally high levels of intrinsic formaldehyde lead to dysfunction in cognition such as learning decline and memory loss. Excess extracellular and intracellular formaldehyde could induce metabolic response and abnormal modifications of cellular proteins such as hydroxymethylation and hyperphosphorylation, protein misfolding, nuclear translocation and even cell death. This cellular response called formaldehyde stress is dependent upon the concentration of formaldehyde. Chronic impairments of the brain resulted from formaldehyde stress could be one of the mechanisms involved in the process of senile dementia during ageing.

Effect of stress and stress hormones on the hormone (insulin) binding of Tetrahymena

The unicellular Tetrahymena pyriformis GL produce, store and secrete vertebrate-like hormones. In earlier experiments the effect of different stressors on the hormone levels of Tetrahymena was studied and an elevation of these was found. In the present experiments the hormone binding was investigated, using flow cytometric method. FITC-insulin binding was elevated after concentrated (5, 10, or 20 mg ml(-1)) NaCl or 0.01%, 0.1%, or 0.05% formaldehyde treatment, or after thermal stress (37 degrees C). Serotonin given together with NaCl increased and together with formaldehyde decreased the binding. Histamine always decreased the binding and insulin was indifferent. Four hours after osmotic stress, hormone binding significantly decreased and this was not influenced by hormones. However, 4 h after formaldehyde stress the binding elevated and this was further increased by repeated hormone treatments. The results show that the stress in Tetrahymena provokes an activation of its hormonal system (hormone production and binding), which is differently influenced by exogeneously given hormones.

Increase of formation of methylamine and formaldehyde in vivo after administration of nicotine and the potential cytotoxicity.

Methylamine is a constituent of cigarette smoke and the major end product of nicotine metabolism. Smoking or nicotine can induce the release of adrenaline, which is in turn deaminated by monoamine oxidase, also producing methylamine. We found that the urinary level of methylamine was significantly elevated following administration of nicotine (25 mg/Kg, i.p.). Semicarbazide-sensitive amine oxidase (SSAO) inhibitors further increased the excretion of methylamine induced by nicotine. Following administration of L-(-)-[N-methyl-3H]nicotine long-lasting irreversible radioactive adducts were detected in different mouse tissues and such adduct formation could be blocked by selective SSAO inhibitors. These adducts are probably cross-linked oligoprotein complexes cross-linked by formaldehyde. The findings support the idea that nicotine can enhance SSAO/methylamine-mediated increase of formaldehyde and oxidative stress and this could in part contribute the adverse effect of health associated with smoking.

Fluctuation of spastic location in patients with vasospastic angina: A quantitative angiographic study: Y. Ozaki, D. Keane, P.W. Serruys. Thoraxcenter, Erasmus University, Rotterdam, The Netherlands. J Am Coll Cardiol 1995;26:1606–14

Better understanding of plant-bacteria interactions under stress is of the prime importance for enhancing airborne pollutant phytoremediation. No studies have investigated plant-epiphyte interactions compared to plant-endophyte interactions under airborne formaldehyde stress in terms of plant Indole-3-acetic acid (IAA), ethylene, reactive oxygen species (ROS) levels and pollutant removal efficiency. Euphorbia milii was inoculated with native plant growth-promoting (PGP) endophytic and epiphytic isolates individually to investigate plant-endophyte compared to plant-epiphyte interactions under continuous formaldehyde fumigation. Under airborne formaldehyde stress, endophyte interacts with its host plant closely and provides higher levels of IAA which protected the plant against formaldehyde phytotoxicity by lowering intracellular ROS, ethylene levels and maintaining shoot epiphytic community; hence, higher pollutant removal. However, plant-epiphyte interactions could not provide enough IAA to confer protection against formaldehyde stress; thus, increased ROS and ethylene levels, large decrease in shoot epiphytic population and lower pollutant removal although epiphyte contacts with airborne pollutant directly (has greater access to gaseous formaldehyde). Endophyte-inoculated plant synthesized more tryptophan as a signaling molecule for its associated bacteria to produce IAA compared to the epiphyte-inoculated one. Under stress, PGP endophyte interacts with its host closely; thus, better protection against stress and higher pollutant removal compared to epiphyte which has limited interactions with the host plant; hence, lower pollutant removal.