Biomedical subjects

M S Santos

Publications and source records attributed to M S Santos.

At least 19 recordsLinked to original sources

PubMed2006

Doxorubicin-induced thiol-dependent alteration of cardiac mitochondrial permeability transition and respiration.

Doxorubicin (DOX) is a highly effective treatment for several forms of cancer. However, clinical experience shows that DOX induces a cumulative and dose-dependent cardiomyopathy that has been ascribed to redox-cycling of the drug on the mitochondrial respiratory chain generating free radicals and oxidative stress in the process. Mitochondrial dysfunction including induction of the mitochondrial permeability transition (MPT) and inhibition of mitochondrial respiration have been implicated as major determinants in the pathogenesis of DOX cardiotoxicity. The present work was aimed at investigating whether the inhibition of mitochondrial respiration occurs secondarily to MPT induction in heart mitochondria isolated from DOX-treated rats and whether one or both consequences of DOX treatment are related with oxidation of protein thiol residues. DOX-induced oxidative stress was associated with the accumulation of products of lipid peroxidation and the depletion of alpha-tocopherol in cardiac mitochondrial membranes. No changes in mitochondrial coenzyme Q9 and Q10 concentrations were detected in hearts of DOX-treated rats. Cardiac mitochondria from DOX-treated rats were more susceptible to diamide-dependent induction of the MPT. Although DOX treatment did not affect state 4 respiration, state 3 respiration was decreased in heart mitochondria isolated from DOX-treated rats, which was reversed in part by adding either cyclosporin A or dithiothreitol, but not Trolox. The results suggest that in DOX-treated rats, (i) induction of the MPT is at least in part responsible for decreased mitochondrial respiration, (ii) heart mitochondria are more susceptible to diamide induced-MPT, (iii) thiol-dependent alteration of mitochondrial respiration is partially reversible ex vivo with dithiothreitol. Collectively, these data are consistent with the thesis that thiol-dependent alteration of MPT and respiration is an important factor in DOX-induced mitochondrial dysfunction.

Animals↗

PubMed2006

Insulin attenuates diabetes-related mitochondrial alterations: a comparative study.

This study evaluated and compared the effect of insulin treatment on the status of brain, heart and kidney mitochondria isolated from 12-week streptozotocin (STZ)-induced diabetic rats versus STZ-diabetic animals treated with insulin during a period of 4 weeks. Mitochondria isolated from 12-week citrate (vehicle)-treated rats were used as control. Several mitochondrial parameters were evaluated: respiratory indexes (state 3 and 4 of respiration, respiratory control and ADP/O ratios), transmembrane potential, depolarization and repolarization levels, ATP, glutathione and coenzyme Q contents, production of hydrogen peroxide, superoxide dismutase, glutathione peroxidase and glutathione reductase activities and the ability of mitochondria to accumulate calcium. We observed that diabetes promoted a significant decrease in kidney and brain mitochondrial coenzyme Q9 content while this parameter was increased in heart mitochondria. Furthermore, diabetes induced a significant increase in hydrogen peroxide production in kidney mitochondria this effect being accompanied by a significant increase in glutathione peroxidase and reductase activities. Furthermore, brain mitochondria isolated from diabetic animals presented a lower ATP content and ability to accumulate calcium. In contrast, heart and kidney mitochondria presented a slight higher capacity to accumulate calcium. Insulin treatment normalized the levels of coenzyme Q9 and glutathione peroxidase and reductase activities and increased ATP content and the ability to accumulate calcium. Altogether these results suggest that insulin treatment attenuates diabetes-induced mitochondrial alterations protecting against the increase in oxidative stress and improving oxidative phosphorylation efficiency. In this line, insulin therapy, besides its well-known importance in the maintenance of glycemic control, may help to protect against mitochondrial dysfunction associated to several age-related disorders such as diabetes.

Animals↗

PubMed2006

The key role of mitochondria in Alzheimer's disease.

Mitochondria are uniquely poised to play a pivotal role in neuronal cell survival or death because they are regulators of both energy metabolism and apoptotic pathways. This review is mainly focused in the discussion of evidence suggesting a clear association between amyloid-beta toxicity, mitochondrial dysfunction, oxidative stress and neuronal damage/death in Alzheimer's disease pathophysiology. The knowledge that mitochondrial dysfunction has a preponderant role in Alzheimer's disease opened a window for new therapeutic strategies aimed to preserve/ameliorate mitochondrial function. Based on recent developments in mitochondrial research, increased pharmacological and pharmaceutical efforts have lead to the emergence of 'Mitochondrial Medicine' as a whole new field of biomedical research being this topic discussed in the last section of this review.

Alzheimer Disease↗

PubMed2004

Effect of streptozotocin-induced diabetes on rat brain mitochondria.

This study evaluated several parameters related to mitochondrial function and oxidative stress in streptozotocin (STZ)-treated rats, a model of type 1 diabetes. For this purpose, the respiratory indexes (RCR and ADP/O ratio), mitochondrial transmembrane potential (DeltaPsim), repolarization lag phase, repolarization level, mitochondrial enzymatic activities, ATP and malondialdehyde (MDA) levels, reduced glutathione (GSH), vitamin E and cardiolipin contents were determined in rat brain mitochondria isolated after 4 and 9 weeks after STZ treatment. Brain mitochondria isolated from citrate (vehicle)-treated Wistar rats were used as control. We observed that STZ-induced diabetes did not substantially affect brain mitochondrial function. Instead, 4-week diabetic rats presented higher mitochondrial respiratory chain enzymatic activities, especially succinate-cytochrome C reductase activity, compared to 4-week control rats. In 9-week diabetic rats, only a significant decrease in cardiolipin content was observed; however, a significant increase in mitochondrial GSH content occurred. All other parameters analysed remained statistically unchanged. From these results, we conclude that STZ-induced diabetes did not promote brain mitochondrial dysfunction, suggesting that oxidative stress associated with type 1 diabetes is not directly related to mitochondrial dysfunction, but probably is related to extramitochondrial factor(s).

Animals↗

PubMed2003

Cholestasis induced by chronic treatment with alpha-naphthyl-isothiocyanate (ANIT) affects rat renal mitochondrial bioenergetics.

Chronic cholestasis is characteristic of many human liver diseases. Renal injury has been often associated with this type of disease. The aim of this study was to evaluate the effect of cholestasis on kidney mitochondrial bioenergetics following in vivo chronic administration of alpha-naphthyl-isothiocyanate (ANIT), a known cholestatic agent. Serum markers of renal injury, kidney morphology and endogenous adenine nucleotides were measured in ANIT-treated rats (80 mg/kg per week s.c. for 16 weeks). Changes in membrane potential and mitochondrial respiration as well as alterations in mitochondrial calcium homeostasis were monitored. Cholestatic animals shown no alterations in renal morphology when compared with control. Additionally, following chronic ANIT administration, no significant alterations in mitochondrial respiratory function have been shown. The phosphorylation capacity of cholestatic kidney mitochondria was enhanced. Associated with these parameters, mitochondria from treated animals exhibited a decreased susceptibility to disruption of mitochondrial calcium homeostasis, due to permeability transition induction. These data suggest that, despite being submitted to chronic treatment with ANIT, kidney mitochondria from cholestasis-induced rats present some defense mechanisms to circumvent this aggression. They show improved phosphorylative capacity and, moreover, a decreased susceptibility to mitochondrial permeability transition induction, probably due to adaptative mechanisms of calcium transport.

1-Naphthylisothiocyanate↗

PubMed2003

Determination of 238U, 234U, 232Th, 228Th, 228Ra, 226Ra and 210Pb concentration in excreta samples of inhabitants of a high natural background area.

The high concentration of uranium and thorium in certain Brazilian areas provides an opportunity to evaluate the radiation exposure due to intake of radionuclides by the populations that live and work in areas with a high natural radiation background. Buena, where this study was conducted, is a small village on the coast in the northern part of Rio de Janeiro State, characterised by the presence of a large deposit of monazite sand. In this paper, the concentrations of 238U, 234U, 232Th, 228Th, 228Ra, 226Ra and 210Pb in faecal samples from inhabitants of this area were determined by a sequential analytical method. The results of the average concentrations in faeces of inhabitants of Buena are 9.4 +/- 3.4 mBq g(ash)(-1) for 238U, 9.2 +/- 4.0 mBq g(ash)(-1) for 234U, 7.0 +/- 4.2 mBq g(ash)(-1) for 232Th, 256.1 +/- 134.6 mBq g(ash)(-1) for 228Th, 335.5 +/- 192.8 mBq g(ash)(-1) for 228Ra, 156.6 +/- 74.1 mBq g(ash)(-1) for 226Ra and 66.7 +/- 17.7 mBq g(ash)(-1) for 210Pb. The results were compared with background concentrations from faecal samples from individuals living in Rio de Janeiro City. For most of the radionuclides analysed, the average concentration in faeces from inhabitants of the high natural radiation background was higher than the concentration found in Rio de Janeiro, considered a 'normal' background area.

Background Radiation↗

PubMed2002

Chromium(VI) interaction with plant and animal mitochondrial bioenergetics: a comparative study.

The mechanism of Cr(VI)-induced toxicity in plants and animals has been assessed for mitochondrial bioenergetics and membrane damage in turnip root and rat liver mitochondria. By using succinate as the respiratory substrate, ADP/O and respiratory control ratio (RCR) were depressed as a function of Cr(VI) concentration. State 3 and uncoupled respiration were also depressed by Cr(VI). Rat mitochondria revealed a higher sensitivity to Cr(VI), as compared to turnip mitochondria. Rat mitochondrial state 4 respiration rate triplicated in contrast to negligible stimulation of turnip state 4 respiration. Chromium(VI) inhibited the activity of the NADH-ubiquinone oxidoreductase (complex I) from rat liver mitochondria and succinate-dehydrogenases (complex II) from plant and animal mitochondria. In rat liver mitochondria, complex I was more sensitive to Cr(VI) than complex II. The activity of cytochrome c oxidase (complex IV) was not sensitive to Cr(VI). Unique for plant mitochondria, exogenous NADH uncoupled respiration was unaffected by Cr(VI), indicating that the NADH dehydrogenase of the outer leaflet of the plant inner membrane, in addition to complexes III and IV, were insensitive to Cr(VI). The ATPase activity (complex V) was stimulated in rat liver mitochondria, but inhibited in turnip root mitochondria. In both, turnip and rat mitochondria, Cr(VI) depressed mitochondrial succinate-dependent transmembrane potential (Deltapsi) and phosphorylation efficiency, but it neither affected mitochondrial membrane permeabilization to protons (H+) nor induced membrane lipid peroxidation. However, Cr(VI) induced mitochondrial membrane permeabilization to K+, an effect that was more pronounced in turnip root than in rat liver mitochondria. In conclusion, Cr(VI)-induced perturbations of mitochondrial bioenergetics compromises energy-dependent biochemical processes and, therefore, may contribute to the basal mechanism underlying its toxic effects in plant and animal cells.

Animals↗

PubMed2001

Lipid peroxidation and aluminium effects on the cholinergic system in nerve terminals.

In the present study, we analyzed how aluminium and oxidative stress induced by ascorbate/Fe(2+) affect the mechanisms related with the cholinergic system in a crude synaptosomal fraction isolated from rat brain. [(3)H]Choline uptake, [(3)H]acetylcholine release, membrane potential and Na(+)/K(+)-ATPase activity were determined in the presence or in the absence of aluminium in control conditions and in the presence of ascorbate (0.8 mM)/Fe(2+) (2.5 micro M). The extent of lipid peroxidation was measured by quantifying thiobarbituric acid reactive substances (TBARS). Under oxidizing conditions aluminium increased the formation of TBARS by about 30%, but was without effect when the synaptosomal preparation was incubated in the absence of oxidants. Additionally, aluminium potentiated the inhibition of the high-affinity [(3)H]choline uptake observed following lipid peroxidation and had the same effect on the Na(+)/K(+)-ATPase activity. [(3)H]Acetylcholine release induced by 4-aminopyridine, and membrane potential were not significantly affected under oxidizing conditions, either in the absence or in the presence of aluminium. We can conclude that aluminium, by potentiating lipid peroxidation, affects the uptake of choline in nerve endings. This effect, occurring during brain oxidative injury, might contribute to the cholinergic dysfunction and neuronal cell degeneration known to occur in Alzheimer's disease.

Journal Article↗

PubMed2001

Glutamate regulates the viability of retinal cells in culture.

In this study, we show that glutamate regulates the viability of cultured retinal cells upon transient glucose deprivation. At low concentrations (10-100 microM) glutamate decreased MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] reduction to about 50% of control and decreased intracellular ATP levels (about 4-fold) after transient glucose removal. Under these conditions, the decrease in MTT reduction was associated with the activation of NMDA (N-methyl-D-aspartate) receptors. Upon exposure to high (10 mM) glutamate and transient glucose deprivation, the intracellular levels of glutamate increased. High glutamate significantly counteracted the decrease in MTT reduction and ATP production observed in the presence of low glutamate concentrations. AOAA (aminooxyacetic acid), a non-specific inhibitor of mitochondrial transaminases, enhanced the intracellular glutamate levels, but did not largely affect glutamate-mediated changes in MTT reduction or ATP production. Furthermore, the intracellular levels of pyruvate were not significantly altered, suggesting that changes in ATP production were not due to an increase in glycolysis. Thus, the recovery from glucose deprivation seems to be facilitated in retinal neuronal cells that had been exposed to high glutamate, in comparison with low glutamate, suggesting a role for high glutamate and glucose in maintaining retinal cell function following conditions of glucose scarcity.

Adenosine Triphosphate↗

PubMed2001

Phylogeography of the human mitochondrial haplogroup L3e: a snapshot of African prehistory and Atlantic slave trade.

The mtDNA haplogroup L3e, which is identified by the restriction site +2349 MboI within the Afro-Eurasian superhaplogroup L3 (-3592 HpaI), is omnipresent in Africa but virtually absent in Eurasia (except for neighbouring areas with limited genetic exchange). L3e was hitherto poorly characterised in terms of HVS-I motifs, as the ancestral HVS-I type of L3e cannot be distinguished from the putative HVS-I ancestor of the entire L3 (differing from the CRS by a transition at np 16223). An MboI screening at np 2349 of a large number of Brazilian and Caribbean mtDNAs (encompassing numerous mtDNAs of African ancestry), now reveals that L3e is subdivided into four principal clades, each characterised by a single mutation in HVS-I, with additional support coming from HVS-II and partial RFLP analysis. The apparently oldest of these clades (transition at np 16327) occurs mainly in central Africa and was probably carried to southern Africa with the Bantu expansion(s). The most frequent clade (transition at np 16320) testifies to a pronounced expansion event in the mid-Holocene and seems to be prominent in many Bantu groups from all of Africa. In contrast, one clade (transition at np 16264) is essentially restricted to Atlantic western Africa (including Cabo Verde). We propose a tentative L3e phylogeny that is based on 197 HVS-I sequences. We conclude that haplogroup L3e originated in central or eastern Africa about 46,000 (+/-14,000) years ago, and was a hitchhiker of much later dispersal and local expansion events, with the rise of food production and iron smelting. Enforced migration of African slaves to the Americas translocated L3e mitochondria, the descendants of which in Brazil and the Caribbean still reflect their different regional African ancestries.

Africa↗

PubMed2001

Decreased susceptibility of heart mitochondria from diabetic GK rats to mitochondrial permeability transition induced by calcium phosphate.

Type 2 diabetes (or non-insulin dependent diabetes mellitus, NIDDM) is a common metabolic disease in man. The Goto-Kakizaki (GK) rat has been designed as a NIDDM model. Previous studies with this strain have shown differences at the mitochondrial level. The mitochondrial permeability transition (MPT) is a widely studied phenomenon but yet poorly understood, that leads to mitochondrial dysfunction and cell death. The aim of this work was to compare the differences in susceptibility of induction of the MPT with calcium phosphate in GK and Wistar rats. Our results show that heart mitochondria from GK rats are less susceptible to the induction of MPT, and show a larger calcium accumulation before the overall loss of mitochondrial impermeability.

Animals↗

PubMed2001

Amyloid beta-peptide promotes permeability transition pore in brain mitochondria.

In this work the effect of the neurotoxic amino acid sequence, Abeta25-35, on brain mitochondrial permeability transition pore (PTP) was studied. For the purpose, the mitochondrial transmembrane potential (deltapsim), mitochondrial respiration and the calcium fluxes were examined. It was observed that Abeta25-35, in the presence of Ca2+, decreased the deltapsim, the capacity of brain mitochondria to accumulate calcium and led to a complete uncoupling of the respiration. However, the reverse sequence of the peptide Abeta25-35 (Abeta35-25) did not promote the PTP. The alterations promoted by Abeta35-25 and/or Ca2+ could be reversed when Ca2 was removed by EGTA or when ADP plus oligomycin were present. The pretreatment with CsA or ADP plus oligomycin prevented the deltapsim drop and preserved the capacity of mitochondria to accumulate Ca2+. These results suggest that Abeta25-35 can promote the PTP induced by Ca2+.

Adenosine Diphosphate↗

PubMed2001

Trafficking of green fluorescent protein tagged-vesicular acetylcholine transporter to varicosities in a cholinergic cell line.

Synaptic vesicle proteins are suggested to travel from the trans-Golgi network to active zones via tubulovesicular organelles, but the participation of different populations of endosomes in trafficking remains a matter of debate. Therefore, we generated a green fluorescent protein (GFP)-tagged version of the vesicular acetylcholine transporter (VAChT) and studied the localization of VAChT in organelles in the cell body and varicosities of living cholinergic cells. GFP-VAChT is distributed to both early and recycling endosomes in the cell body and is also observed to accumulate in endocytic organelles within varicosities of SN56 cells. GFP-VAChT positive organelles in varicosities are localized close to plasma membrane and are labeled with FM4-64 and GFP-Rab5, markers of endocytic vesicles and early endosomes, respectively. A GFP-VAChT mutant lacking a dileucine endocytosis motif (leucine residues 485 and 486 changed to alanine residues) accumulated at the plasma membrane in SN56 cells. This endocytosis-defective GFP-VAChT mutant is localized primarily at the somal plasma membrane and exhibits reduced neuritic targeting. Furthermore, the VAChT mutant did not accumulate in varicosities, as did VAChT. Our data suggest that clathrin-mediated internalization of VAChT to endosomes at the cell body might be involved in proper sorting and trafficking of VAChT to varicosities. We conclude that genesis of competent cholinergic secretory vesicles depends on multiple interactions of VAChT with endocytic proteins.

Acetylcholine↗

PubMed2001

Enhanced mitochondrial testicular antioxidant capacity in Goto-Kakizaki diabetic rats: role of coenzyme Q.

Because diabetes mellitus is associated with impairment of testicular function, ultimately leading to reduced fertility, this study was conducted to evaluate the existence of a cause-effect relationship between increased oxidative stress in diabetes and reduced mitochondrial antioxidant capacity. The susceptibility to oxidative stress and antioxidant capacity (in terms of glutathione, coenzyme Q, and vitamin E content) of testis mitochondrial preparations isolated from Goto-Kakizaki (GK) non-insulin-dependent diabetic rats and from Wistar control rats, 1 yr of age, was evaluated. It was found that GK mitochondrial preparations showed a lower susceptibility to lipid peroxidation induced by ADP/Fe(2+), as evaluated by oxygen consumption and reactive oxygen species generation. The decreased susceptibility to oxidative stress in diabetic rats was associated with an increase in mitochondrial glutathione and coenzyme Q9 contents, whereas vitamin E was not changed. These results demonstrate a higher antioxidant capacity in diabetic GK rats. We suggest this is an adaptive response of testis mitochondria to the increased oxidative damage in diabetes mellitus.

Animals↗

PubMed2001

Denitrification on the top of UASB reactors of rice wastewaters.

Parboiled rice industry is one of main food industries in the south of Brazil. The main parts of the processing are the humidification and gelatinization of the grain. This procedure increases the productivity and nutritive and cooking values of the product. Some of these industries in the region utilize upflow anaerobic sludge blanket (UASB) reactors as a biological treatment for carbon removal. For nitrogen removal, the proposed system aims to eliminate an extra denitrification reactor, making this step in the top of the UASB, an anoxic zone of the reactor. Nitrification was performed in aerated mixed reactor of 3.6 L.A fraction of the NR was recycled in the top of UASB reactor above the sludge blanket. Recycled ratio varied from 0; 1:0.5; 1:1.0; to 1:1.5. The maximum removal efficiency of NTK was 80%. The results confirm the viability of the proposed system for denitrification.

Bacteria, Anaerobic↗

PubMed2000

Synaptosomes isolated from Goto-Kakizaki diabetic rat brain exhibit increased resistance to oxidative stress: role of vitamin E.

Increased oxidative stress is believed to be an important factor in the development of diabetic complications. In this study, the effect of diabetes on the susceptibility of synaptosomes to oxidative stress, induced by the oxidizing system ascorbate/Fe2+, on the activity of antioxidant enzymes and on the levels of glutathione and vitamin E was investigated. Synaptosomes were isolated from brain of 29-weeks-old Goto-Kakizaki (GK) rats, a model of non-insulin dependent diabetes mellitus and from normal Wistar rats. Synaptosomes isolated from GK rats displayed a lower susceptibility to lipid peroxidation, as assessed by quantifying thiobarbituric acid reactive substances (TBARS), than normal rats (5.33 +/- 0.79 and 7.58 +/- 0.7 nmol TBARS/mg protein, respectively). In the absence of oxidants, no significant differences were found between the levels of peroxidation in synaptosomes of diabetic or control rats. Superoxide dismutase (SOD), glutathione peroxidase and glutathione reductase activities were unaltered in the brain of diabetic rats. There were no statistically significant differences in fatty acid composition of total lipids and reduced glutathione levels in synaptosomes of diabetic and control rats. The decreased susceptibility to membrane lipid peroxidation of diabetic rats synaptosomes correlated with a 1.3-fold increase in synaptosomal vitamin E levels. Vitamin E levels in plasma were also higher in diabetic rats (21.32 micromol/l) as compared to normal rats (15.13 micromol/l). We conclude that the increased resistance to lipid peroxidation in GK rat brain synaptosomes may be due to the increased vitamin E content, suggesting that diabetic animals might develop enhanced defense systems against brain oxidative stress.

Animals↗

PubMed2000

Susceptibility to beta-amyloid-induced toxicity is decreased in goto-kakizaki diabetic rats: involvement of oxidative stress.

The response of synaptosomes isolated from Wistar non-diabetic rats and Goto-Kakizaki (GK) diabetic rats to the beta-amyloid fragment Abeta25-35 was compared. The synaptosomal redox activity, evaluated by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, was shown to be decreased in GK rats (72.8 +/- 7.45% of MTT reduction). However, the reduction of MTT was decreased in synaptosomes of Wistar rats upon Abeta25-35 treatment (84.47 +/- 3.73%), while in GK rats it was not affected. Abeta25-35 induced lipid peroxidation in synaptosomes of Wistar rats, but not in that of GK rats, leading to an 1.5-fold increase in thiobarbituric acid reactive substances (TBARS) levels. In the absence of Abeta25-35, basal TBARS levels were 1.6-fold higher in GK rats. In the former preparations, the content in vitamin E was also higher (2-fold). A decrease in ATP levels, of about 2-fold, was observed in synaptosomes of Wistar rats treated with Abeta25-35, while no significant changes were observed in synaptosomes of GK rats. No significant differences between the two groups were detected in the basal ATP levels. The extrasynaptosomal accumulation of aspartate and glutamate increased upon Abeta25-35 treatment, only in synaptosomes of Wistar rats (aspartate and glutamate accumulation increased by 1.1-fold and 1.5-fold, respectively), while the accumulation of glycine increased in both Wistar (by 1.8-fold) and GK (by 2.2-fold) rats. No statistical differences in the basal accumulation of aminoacids were observed. These results show that synaptosomes of GK diabetic rats have a lower redox activity, but are less susceptible to the Abeta25-35-induced toxicity. Data also suggest that oxidative stress occurs in this hyperglycemia animal model and that an increase in the antioxidant defense systems may exert protection against toxic insults. This mechanism, occuring in the early phases of diabetes, may correspond to an adaptive response.

Adenine Nucleotides↗

PubMed2000

Glutamate-mediated inhibition of oxidative phosphorylation in cultured retinal cells.

Glutamate is an excitotoxin responsible for causing neuronal damage associated with mitochondria dysfunction. We have analyzed the relationship between the mitochondrial respiratory rate, the membrane potential (delta psi) and the activity of mitochondrial complexes in retinal cells in culture, used as neuronal models. Glutamate (10 microM-10 mM) dose-dependently decreased the O2 consumption and the membrane potential. A linear correlation was found between these parameters, suggesting that the mitochondrial respiratory function was affected. Exposure to glutamate (100 microM) for 10 min, in the absence of Mg2+, inhibited the activity of complex I (26.3%), complexes II/III (22.2%) and complex IV (26.7%). MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine hydrogen maleate), a non-competitive antagonist of the NMDA (N-methyl-D-aspartate) receptors, completely reversed the effect exerted by 100 microM glutamate at the level of complexes I, II/III and IV. These results suggest that NMDA receptor-mediated inhibition of mitochondrial respiratory chain complexes may be responsible for the alteration in the respiratory rate of chick retinal cells submitted to glutamate.

Animals↗