共查询到20条相似文献,搜索用时 46 毫秒
1.
Henriqueta Dias Cardoso Eraldo Fonseca dos Santos Junior David Filipe de Santana Catarina Gonçalves-Pimentel Monara Kaélle Angelim Alinny R. Isaac Cláudia Jacques Lagranha Rubem Carlos Araújo Guedes Eduardo Isidoro Beltrão Edgar Morya Marcelo Cairrão Araújo Rodrigues Belmira Lara da Silveira Andrade-da-Costa 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
Our previous study demonstrated that essential fatty acid (EFA) dietary restriction over two generations induced midbrain dopaminergic cell loss and oxidative stress in the substantia nigra (SN) but not in the striatum of young rats. In the present study we hypothesized that omega-3 deficiency until adulthood would reduce striatum's resilience, increase nitric oxide (NO) levels and the number of BDNF-expressing neurons, both potential mechanisms involved in SN neurodegeneration.Methods
Second generation rats were raised from gestation on control or EFA-restricted diets until young or adulthood. Lipoperoxidation, NO content, total superoxide dismutase (t-SOD) and catalase enzymatic activities were assessed in the SN and striatum. The number of tyrosine hydroxylase (TH)- and BDNF-expressing neurons was analyzed in the SN.Results
Increased NO levels were observed in the striatum of both young and adult EFA-deficient animals but not in the SN, despite a similar omega-3 depletion (~ 65%) in these regions. Increased lipoperoxidation and decreased catalase activity were found in both regions, while lower tSOD activity was observed only in the striatum. Fewer TH- (~ 40%) and BDNF-positive cells (~ 20%) were detected at the SN compared to the control.Conclusion
The present findings demonstrate a differential effect of omega-3 deficiency on NO production in the rat's nigrostriatal system. Prolonging omega-3 depletion until adulthood impaired striatum's anti-oxidant resources and BDNF distribution in the SN, worsening dopaminergic cell degeneration.General significance
Omega-3 deficiency can reduce the nigrostriatal system's ability to maintain homeostasis under oxidative conditions, which may enhance the risk of Parkinson's disease. 相似文献2.
Hoon Jae Jeong Dae Young Yoo Dae Won Kim Hyeon Ji Yeo Su Bin Cho Jiye Hyeon Jung Hwan Park Jinseu Park Won Sik Eum Hyun Sook Hwang Moo-Ho Won In Koo Hwang Soo Young Choi 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
Oxidative stress is a leading cause of various diseases, including ischemia and inflammation. Peroxiredoxin2 (PRX2) is one of six mammalian isoenzymes (PRX1–6) that can reduce hydrogen peroxide (H2O2) and organic hydroperoxides to water and alcohols.Methods
We produced PEP-1-PRX2 transduction domain (PTD)-fused protein and investigated the effect of PEP-1-PRX2 on oxidative stress-induced neuronal cell death by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Western blot, immunofluorescence microscopy, and immunohistochemical analysis.Results
Our data showed that PEP-1-PRX2, which can effectively transduce into various types of cells and brain tissues, could be implicated in suppressing generation of reactive oxygen species, preventing depolarization of the mitochondrial membrane, and inhibiting the apoptosis pathway in H2O2-stimulated HT22, murine hippocampal neuronal cells, likely resulting in protection of HT22 cells against H2O2-induced toxicity. In addition, we found that in a transient forebrain ischemia model, PEP-1-PRX2 inhibited the activation of astrocytes and microglia in the CA1 region of the hippocampus and lipid peroxidation and also prevented neuronal cell death against ischemic damage.Conclusions
These findings suggest that the transduced PEP-1-PRX2 has neuroprotective functions against oxidative stress-induced cell death in vitro and in vivo.General significance
PEP-1-PRX2 could be a potential therapeutic agent for oxidative stress-induced brain diseases such as ischemia. 相似文献3.
Fatemeh Shaki Mir-Jamal Hosseini Mahmoud Ghazi-Khansari Jalal Pourahmad 《Biochimica et Biophysica Acta (BBA)/General Subjects》2012
Background
Kidney is known as the most sensitive target organ for depleted uranium (DU) toxicity in comparison to other organs. Although the oxidative stress and mitochondrial damage induced by DU has been well investigated, the precise mechanism of DU-induced nephrotoxicity has not been thoroughly recognized yet.Methods
Kidney mitochondria were obtained using differential centrifugation from Wistar rats and mitochondrial toxicity endpoints were then determined in both in vivo and in vitro uranyl acetate (UA) exposure cases.Results
Single injection of UA (0, 0.5, 1 and 2 mg/kg, i.p.) caused a significant increase in blood urea nitrogen and creatinine levels. Isolated mitochondria from the UA-treated rat kidney showed a marked elevation in oxidative stress accompanied by mitochondrial membrane potential (MMP) collapse as compared to control group. Incubation of isolated kidney mitochondria with UA (50, 100 and 200 μM) manifested that UA can disrupt the electron transfer chain at complex II and III that leads to induction of reactive oxygen species (ROS) formation, lipid peroxidation, and glutathione oxidation. Disturbances in oxidative phosphorylation were also demonstrated through decreased ATP concentration and ATP/ADP ratio in UA-treated mitochondria. In addition, UA induced a significant damage in mitochondrial outer membrane. Moreover, MMP collapse, mitochondrial swelling and cytochrome c release were observed following the UA treatment in isolated mitochondria.General significance
Both our in vivo and in vitro results showed that UA-induced nephrotoxicity is linked to the impairment of electron transfer chain especially at complex II and III which leads to subsequent oxidative stress. 相似文献4.
Giuseppe Maulucci Diana Troiani Sara Letizia Maria Eramo Fabiola Paciello Maria Vittoria Podda Gaetano Paludetti Massimiliano Papi Alessandro Maiorana Valentina Palmieri Marco De Spirito Anna Rita Fetoni 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
Noise exposure impairs outer hair cells (OHCs). The common basis for OHC dysfunction and loss by acoustic over-stimulation is represented by reactive oxygen species (ROS) overload that may affect the membrane structural organization through generation of lipid peroxidation.Methods
Here we investigated in OHC different functional zones the mechanisms linking metabolic functional state (NAD(P)H intracellular distribution) to the generation of lipid peroxides and to the physical state of membranes by two photon fluorescence microscopy.Results
In OHCs of control animals, a more oxidized NAD(P)H redox state is associated to a less fluid plasma membrane structure. Acoustic trauma induces a topologically differentiated NAD(P)H oxidation in OHC rows, which is damped between 1 and 6 h. Peroxidation occurs after ~ 4 h from noise insult, while ROS are produced in the first 0.2 h and damage cells for a period of time after noise exposure has ended (~ 7.5 h) when a decrease of fluidity of OHC plasma membrane occurs. OHCs belonging to inner rows, characterized by a lower metabolic activity with respect to other rows, show less severe metabolic impairment.Conclusions
Our data indicate that plasma membrane fluidity is related to NAD(P)H redox state and lipid peroxidation in hair cells.General Significance
Our results could pave the way for therapeutic intervention targeting the onset of redox umbalance. 相似文献5.
Vuyisile S. Thibane Ruan Ells Arno Hugo Jacobus Albertyn Walter J. Janse van Rensburg Pieter W.J. Van Wyk Johan L.F. Kock Carolina H. Pohl 《Biochimica et Biophysica Acta (BBA)/General Subjects》2012
Background
Polyunsaturated fatty acids (PUFAs) have antifungal properties, but the mode by which they induce their action is not always clear. The aim of the study was to investigate apoptosis as a mode of action of antifungal PUFAs (stearidonic acid, eicosapentaenoic acid and docosapentaenoic acid) which are inhibitory towards biofilm formation of C. albicans and C. dubliniensis.Methods
Candida biofilms were grown in the absence or presence of 1 mM PUFAs (linoleic acid, stearidonic acid, eicosapentaenoic acid, docosapentaenoic acid) for 48 h at 37 °C. The effect of these PUFAs on the membrane fatty acid profile and unsaturation index, oxidative stress, mitochondrial transmembrane potential and apoptosis was evaluated.Results
When biofilms of C. albicans and C. dubliniensis were exposed to certain PUFAs there was an increase in unsaturation index of the cellular membranes and accumulation of intracellular reactive oxygen species (ROS). This resulted in apoptosis, evidenced by reduced mitochondrial membrane potential and nuclear condensation and fragmentation. The most effective PUFA was stearidonic acid.Conclusions
The resultant cell death of both C. albicans and C. dubliniensis is due to apoptosis.General significance
Due to the increase in drug resistance, alternative antifungal drugs are needed. A group of natural antifungal compounds is PUFAs. However, understanding their mechanisms of action is important for further use and development of these compounds as antifungal drugs. This paper provides insight into a possible mode of action of antifungal PUFAs. 相似文献6.
Lifan Shih Youngran ChungRenuka Sriram Thomas Jue 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
Previous studies have shown that palmitate (PA) can bind specifically and non-specifically to Fe(III) MbCN. The present study has observed PA interaction with physiological states of Fe(II) Mb, and the observations support the hypothesis that Mb may have a potential role in facilitating intracellular fatty acid transport.Methods
1H NMR spectra measurements of the Mb signal during PA titration show signal changes consistent with specific and non-specific binding.Results
Palmitate (PA) interacts differently with physiological states of Mb. Deoxy Mb does not interact specifically or non-specifically with PA, while the carbonmonoxy myoglobin (MbCO) interaction with PA decreases the intensity of selective signals and produces a 0.15 ppm upfield shift of the PA methylene peak. The selective signal change upon PA titration provides a basis to determine an apparent PA binding constant, which serves to create a model comparing the competitive PA binding and facilitated fatty acid transport of Mb and fatty acid binding protein (FABP).Conclusions
Given contrasting PA interaction of ligated vs. unligated Mb, the cellular fatty acid binding protein (FABP) and Mb concentration in the cell, the reported cellular diffusion coefficients, the PA dissociation constants from ligated Mb and FABP, a fatty acid flux model suggests that Mb can compete with FABP transporting cellular fatty acid.General significance
Under oxygenated conditions and continuous energy demand, Mb dependent fatty acid transport could influence the cell's preference for carbohydrate or fatty acid as a fuel source and regulate fatty acid metabolism. 相似文献7.
Background
Brain lipid peroxidation has long been considered a potential therapeutic target for Alzheimer's disease (AD). β-sitosterol (BS), a plant sterol that is prevalent in plant plasma membrane, has been suggested to have antioxidant activity. Previous studies have demonstrated that dietary BS can enter the brain and accumulates in the plasma membrane of brain cells. However, it is unknown whether and how BS exerts its antioxidant activity in plasma membrane.Methods
To incorporate BS into the plasma membrane in vitro, HT22 cells and primarily cultured hippocampal cells were supplemented with BS using 2-hydroxypropyl-β-cyclodextrin (HPβCD) as a carrier. The present study then tested the antioxidant effect of membrane BS against glucose oxidase (GOX)-induced oxidative stress and lipid peroxidation, and whether the antioxidant effect of membrane BS was associated with estrogen receptor (ER)-mediated phosphatidyl inositol 3-kinase (PI3K)/glycogen synthase kinase 3 (GSK3β) signaling.Results
Incorporation of BS into cell membrane prevented GOX-induced oxidative stress and lipid peroxidation, which could be suppressed by the ER antagonists and PI3K inhibitor. Additional experiments showed that incorporation of BS into cell membrane induced an up-regulation of PI3K activity and a recruitment of PI3K to lipid rafts, which could be inhibited by the ER antagonist. Membrane BS also increased the expression of p-GSK3β, which could be suppressed in the presence of the ER antagonist and PI3K inhibitor.General significance
Given that BS is prevalent in foods such as plant oil, the results provide a better understanding of the beneficial effects of these BS-enriched nutrients on neurodegenerative diseases such as AD. 相似文献8.
Tomonari Saito Chikako NitoMasayuki Ueda Toshiki InabaFumio Kamiya Kanako MuragaKen-ichiro Katsura Yasuo Katayama 《Life sciences》2014
Aims
Pre-treatment with statins is known to ameliorate ischemic brain damage after experimental stroke, and is independent of cholesterol levels. We undertook pre- vs post-ischemic treatment with atorvastatin after focal cerebral ischemia in rats.Main methods
Male Sprague–Dawley rats underwent transient 90-min middle cerebral artery occlusion (MCAO). Atorvastatin (20 mg/kg/day) or vehicle was administered orally. Rats were divided into vehicle-treated, atorvastatin pre-treatment, atorvastatin post-treatment, and atorvastatin continuous-treatment groups. In the pre-treatment, rats were given atorvastatin or vehicle for 7 days before MCAO. In the post-treatment, rats received atorvastatin or vehicle for 7 days after MCAO. Measurement of infarct volume, as well as neurological and immunohistochemical assessments, were done 24 h and 7 days after reperfusion.Key findings
Each atorvastatin-treated group demonstrated significant reductions in infarct and edema volumes compared with the vehicle-treated group 24 h after reperfusion. Seven days after reperfusion, infarct volumes in the post-treatment group and continuous-treatment group (but not the pre-treatment group) were significantly smaller than in the vehicle-treated group. Only the continuous-treatment group had significantly improved neurological scores 7 days after reperfusion compared with the vehicle group. Post-treatment and continuous-treatment groups had significantly decreased lipid peroxidation, oxidative DNA damage, microglial activation, expression of tumor necrosis factor-alpha, and neuronal damage in the cortical ischemic boundary area after 7 days of reperfusion.Significance
These results suggest that continuous oral administration (avoiding withdrawal) with statins after stroke may reduce the extent of post-ischemic brain damage and improve neurological outcome by inhibiting oxidative stress and inflammatory responses. 相似文献9.
10.
Henrik E. Poulsen Laia Llovera Nadal Kasper Broedbaek Peter E. Nielsen Allan Weimann 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
DNA and RNA oxidations have been linked to diseases such as cancer, arteriosclerosis, neurodegeneration and diabetes. The prototype base modification studied is the 8-hydroxylation of guanine. DNA integrity is maintained by elaborate repair systems and RNA integrity is less studied but relies mainly on degradation.Scope of review
DNA and RNA oxidations are measured by very similar techniques. The scope of this review is to highlight the preferred methods of measurement of oxidized nucleic acid metabolites, to highlight novel findings particularly in RNA oxidation, and to present the interpretation of the measurements.Major conclusions
Tissue levels are snap-shots of the level in a specific organ or cell system and reflect the balance between formation rate and elimination rate (repair), and must be interpreted as such. Urinary excretion is a global measure of oxidative stress in an organism and is therefore best suited for situations or diseases where large parts or the entire organism is stressed by oxidation. It represents the body average rate by which either RNA or DNA is oxidized and is interpreted as oxidative stress. Oxidations of RNA and DNA precursors have been demonstrated and the quantitative importance is debated.General significance
Careful experimental designs and appropriate choice of methodology are paramount for correct testing of hypotheses related to oxidative stress, and pitfalls are plentiful. There is accumulating evidence that DNA oxidation is associated with disease, particularly cancer, and recent evidence points at an association between RNA oxidation and neurodegenerative diseases and diabetes. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn. 相似文献11.
Kavitha Swaminathan S. Mathan Kumar Dahn L. Clemens Aparajita Dey 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
In recent years, there has been a growing interest to explore the association between liver injury and diabetes. Advanced glycated end product (AGE) formation which characterizes diabetic complications is formed through hyperglycemia mediated oxidative stress and is itself a source for ROS. Further, in VL-17A cells over-expressing ADH and CYP2E1, greatly increased oxidative stress and decreased viability have been observed with high glucose exposure.Methods
In VL-17A cells treated with high glucose and pretreated with the different inhibitors of ADH and CYP2E1, the changes in cell viability, oxidative stress parameters and formation of AGE, were studied.Results
Inhibition of CYP2E1 with 10 μM diallyl sulfide most effectively led to decreases in the oxidative stress and toxicity as compared with ADH inhibition with 2 mM pyrazole or the combined inhibition of ADH and CYP2E1 with 5 mM 4-methyl pyrazole. AGE formation was decreased in VL-17A cells when compared with HepG2 cells devoid of the enzymes. Further, AGE formation was decreased to the greatest extent with the inhibitor for CYP2E1 suggesting that high glucose inducible CYP2E1 and the consequent ROS aid AGE formation.Conclusions
Thus, CYP2E1 plays a pivotal role in the high glucose induced oxidative stress and toxicity in liver cells as observed through direct evidences obtained utilizing the different inhibitors for ADH and CYP2E1.General significance
The study demonstrates the role of CYP2E1 mediated oxidative stress in aggravating hyperglycemic insult and suggests that CYP2E1 may be a vital component of hyperglycemia mediated oxidative injury in liver. 相似文献12.
Li-Chen Ge Zhuo-Jia Chen Hao Liu Kun-Shui Zhang Qiao Su Xiang-Yu Ma Hong-Bin Huang Zhen-Dong Zhao Yu-Ye Wang John P. Giesy Jun Du Hong-Sheng Wang 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
Biphasic effects on cell proliferation of bisphenol A (BPA) can occur at lesser or greater exposures. Sertoli cells play a pivotal role in supporting proliferation and differentiation of germ cells. The mechanisms responsible for inverse effects of great and low concentrations of BPA on Sertoli cell proliferation need further study.Methods
We utilized proteomic study to indentify the protein expression changes of Sertoli TM4 cells treated with 10− 8 M and 10− 5 M BPA. The further mechanisms related to mitochondria, energy metabolism and oxidative stress were investigated by qRT-PCR and Western-blotting analysis.Results
Proteomic studies identified 36 proteins and two major clusters of proteins including energy metabolism and oxidative stress expressed with opposite changes in Sertoli cells treated with 10− 8 M and 10− 5 M BPA, respectively, for 24 h. Exposure to 10− 5 M BPA resulted in greater oxidative stress and then inhibited cell proliferation, while ROS scavenger NAC effectively blocked these effects. Exposure to 10− 8 M BPA caused higher intercellular ATP, greater activities of mitochondria, and resulted in significant proliferation of TM4 cells, while oligomycin A, an inhibitor of ATP synthase, abolished these growth advantages.Conclusions
Our study demonstrated that micromolar BPA inhibits proliferation of Sertoli cells by elevating oxidative stress while nanomolar BPA stimulates proliferation by promoting energy metabolism.General significance
Micromolar BPA inhibits cell proliferation by elevating oxidative stress while nanomolar BPA stimulates cell proliferation by promoting energy metabolism. 相似文献13.
Maria del Carmen Vazquez-Pedrazuela Maria-Belen Canton-Alvarez Maria del Carmen de la Fuente-Hontañon Angel Soloaga-Morales Jose-Maria Collazos-del Castillo Roberto Sertal-Parcero 《Revista espa?ola de geriatría y gerontología》2012
Introduction
The aim of this study is to establish the prevalence of vitamin B12 and folic acid deficiency in the population of 65 years and over in semi-urban and rural area, as well as investigating the risk factors, and the determining factors of this deficiency in this population and its relationship with the prevalence of concomitant cardiovascular and cognitive diseases.Materials and methods
A cross-sectrionall study conducted in the Geriatrics Outpatients in the period between 2008 and 2010. Demographic, clinical and laboratory were collected at 3 different times.A bivariate analysis was performed with lack of vitamin B12 and folic acid, as the outcome variables.Results
Vitamin B12 defieciency was found in 16.5% of the sample, and no folic acid deficiency. A strong association was found with vitamin B12 deficiency and cardiac and cerebrovascular diseases, vascular risk factors and drugs administered in prevention of cardiac events and ischaemic stroke.Conclusions
There was a higher prevalence of vitamin B12 deficiency in the elderly population in the catchment area of Medina del Campo compared to that found in the literature, but not so with the isolated deficiency of folic acid. 相似文献14.
Hiroaki Akasaka Ryohei Sasaki Kenji Yoshida Izumi Takayama Toyofumi Yamaguchi Hiromi Yoshida Yoshiyuki Mizushina 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
Gemcitabine (GEM) is used to treat various carcinomas and represents an advance in pancreatic cancer treatment. In the screening for DNA polymerase (pol) inhibitors, a glycoglycerolipid, monogalactosyl diacylglycerol (MGDG), was isolated from spinach.Methods
Phosphorylated GEM derivatives were chemically synthesized. In vitro pol assay was performed according to our established methods. Cell viability was measured using MTT assay.Results
Phosphorylated GEMs inhibition of mammalian pol activities assessed, with the order of their effect ranked as: GEM-5′-triphosphate (GEM-TP) > GEM-5′-diphosphate > GEM-5′-monophosphate > GEM. GEM suppressed growth in the human pancreatic cancer cell lines BxPC-3, MIAPaCa2 and PANC-1 although phosphorylated GEMs showed no effect. MGDG suppressed growth in these cell lines based on its selective inhibition of replicative pol species. Kinetic analysis showed that GEM-TP was a competitive inhibitor of pol α activity with nucleotide substrates, and MGDG was a noncompetitive inhibitor with nucleotide substrates. GEM combined with MGDG treatments revealed synergistic effects on the inhibition of DNA replicative pols α and γ activities compared with GEM or MGDG alone. In cell growth suppression by GEM, pre-addition of MGDG significantly enhanced cell proliferation suppression, and the combination of these compounds was found to induce apoptosis. In contrast, GEM-treated cells followed by MGDG addition did not influence cell growth.Conclusions
GEM/MGDG enhanced the growth suppression of cells based on the inhibition of pol activities.General significance
Spinach MGDG has great potential for development as an anticancer food compound and could be an effective clinical anticancer chemotherapy in combination with GEM. 相似文献15.
S. Sreenivasa Reddy Karnam ShruthiV. Sudhakar Reddy G. RaghuP. Suryanarayana N.V. GiridharanG. Bhanuprakash Reddy 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
Obesity is associated with various progressive age-related diseases, including neurological disorders. However, underlying molecular basis for increased risk of neurodegeneration in obesity is unknown. A suitable animal model would immensely help in understanding the obesity-linked neurological problems.Methods
A spontaneously developed obese rat (WNIN/Ob) which is highly vulnerable for a variety of degenerative diseases was isolated from the existing WNIN stock rats. Ultrastructure of neurons in the cerebral cortex of 12-month old obese rats was evaluated by transmission electron microscopy. qRT-PCR and immunoblotting of ubiquitin C-terminal hydrolases (UCHs), ubiquitin, proteasomal sub-units, markers of ER stress and apoptosis were performed in the cerebral cortex. Proteasome activity was assayed by fluorometric method. Immunohistochemistry was performed for mediators of apoptosis, which was further confirmed by TUNEL assay. These investigations were also carried in high-fat diet-induced obese rat model.Results
Neurons in the cerebral cortex of 12-month obese rats showed swollen mitochondria, disrupted ER and degenerating axons, nucleus and finally neurons. Results showed altered UPS, existence of ER stress, up-regulation of apoptotic markers and apoptosis in the cerebral cortex of obese rats. It appears that UCHL-1 mediated apoptosis through stabilizing p53 might play a role in neuronal cell death in obese rat. Similar changes were observed in the brain of diet-induced obese WNIN rats.Conclusion
Altered UPS could be one of the underlying mechanisms for the neuronal cell death in obese conditions.General significance
This is the first report to highlight the role of altered UPS in neurodegeneration due to obesity. 相似文献16.
Matthew J. Bird David R. Thorburn Ann E. Frazier 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
The neuropathology of mitochondrial disease is well characterised. However, pathophysiological mechanisms at the level of biochemistry and cell biology are less clear. Progress in this area has been hampered by the limited accessibility of neurologically relevant material for analysis.Scope of review
Here we discuss the recent development of a variety of model systems that have greatly extended our capacity to understand the biochemical features associated with mitochondrial neuropathology. These include animal and cell based models, with mutations in both nuclear and mitochondrial DNA encoded genes, which aim to recapitulate the neuropathology and cellular biochemistry of mitochondrial diseases.Major conclusions
Analysis of neurological tissue and cells from these models suggests that although there is no unifying mode of pathogenesis, dysfunction of the oxidative phosphorylation (OXPHOS) system is often central. This can be associated with altered reactive oxygen species (ROS) generation, disruption of the mitochondrial membrane potential (ΔΨm) and inadequate ATP synthesis. Thus, other cellular processes such as calcium (Ca2 +) homeostasis, cellular signaling and mitochondrial morphology could be altered, ultimately compromising viability of neuronal cells.General significance
Mechanisms of neuronal dysfunction in mitochondrial disease are only just beginning to be characterised, are system dependent and complex, and not merely driven by energy deficiency. The diversity of pathogenic mechanisms emphasises the need for characterisation in a wide range of models, as different therapeutic strategies are likely to be needed for different diseases.This article is part of a Special Issue entitled Frontiers of Mitochondrial Research. 相似文献17.
Martina Wallace Helena WhelanLorraine Brennan 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
Chronic exposure to hyperglycaemic conditions has been shown to have detrimental effects on beta cell function. The resulting glucotoxicity is a contributing factor to the development of type 2 diabetes. The objective of this study was to combine a metabolomics approach with functional assays to gain insight into the mechanism by which glucotoxicity exerts its effects.Methods
The BRIN-BD11 and INS-1E beta cell lines were cultured in 25 mM glucose for 20 h to mimic glucotoxic effects. PDK-2 protein expression, intracellular glutathione levels and the change in mitochondrial membrane potential and intracellular calcium following glucose stimulation were determined. Metabolomic analysis of beta cell metabolite extracts was performed using GC–MS, 1H NMR and 13C NMR.Results
Conditions to mimic glucotoxicity were established and resulted in no loss of cellular viability in either cell line while causing a decrease in insulin secretion. Metabolomic analysis of beta cells following exposure to high glucose revealed a change in amino acids, an increase in glucose and a decrease in phospho-choline, n−3 and n−6 PUFAs during glucose stimulated insulin secretion relative to cells cultured under control conditions. However, no changes in calcium handling or mitochondrial membrane potential were evident.Conclusions
Results indicate that a decrease in TCA cycle metabolism in combination with an alteration in fatty acid composition and phosphocholine levels may play a role in glucotoxicity induced impairment of glucose stimulated insulin secretion.General significance
Alterations in certain metabolic pathways play a role in glucotoxicity in the pancreatic beta cell. 相似文献18.
19.
Ashutosh Pandey Swati Chandra Lalit Kumar Singh Chauhan Gopeshwar Narayan Debapratim Kar Chowdhuri 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
Amorphous silica nanoparticles (aSNPs) are used for various applications including food industry. However, limited in vivo studies are available on absorption/internalization of ingested aSNPs in the midgut cells of an organism. The study aims to examine cellular uptake of aSNPs (< 30 nm) in the midgut of Drosophila melanogaster (Oregon R+) owing to similarities between the midgut tissue of this organism and human and subsequently cellular stress response generated by these nanoparticles.Methods
Third instar larvae of D. melanogaster were exposed orally to 1–100 μg/mL of aSNPs for 12–36 h and oxidative stress (OS), heat shock genes (hsgs), membrane destabilization (Acridine orange/Ethidium Bromide staining), cellular internalization (TEM) and apoptosis endpoints.Results
A significant increase was observed in OS endpoints in the midgut cells of exposed Drosophila in a concentration- and time-dependent manner. Significantly increased expression of hsp70 and hsp22 along with caspases activation, membrane destabilization and mitochondrial membrane potential loss was also observed. TEM analysis showed aSNPs-uptake in the midgut cells of exposed Drosophila via endocytic vesicles and by direct membrane penetration.Conclusion
aSNPs after their internalization in the midgut cells of exposed Drosophila larvae show membrane destabilization along with increased cellular stress and cell death.General significance
Ingested aSNPs show adverse effects on the cells of GI tract of the exposed organism thus their industrial use as a food-additive may raise concern to human health. 相似文献20.