ali akbar Meratan - Academia.edu (original) (raw)

Papers by ali akbar Meratan

PLOS ONE, Dec 23, 2020

There are many reports demonstrating that various derivatives of carbon nanoparticles are effecti... more There are many reports demonstrating that various derivatives of carbon nanoparticles are effective inhibitors of protein aggregation. As surface structural features of nanoparticles play a key role on modulating amyloid fibrillation process, in the present in vitro study, bovine insulin and hen egg white lysozyme (HEWL) were selected as two model proteins to investigate the reducing effect of graphene oxide quantum dots (GOQDs) on their assembly under amyloidogenic conditions. GOQDs were prepared through direct pyrolysis of citric acid, and the reduction step was carried out using ascorbic acid. The prepared nanoparticles were characterized by UV-Vis, X-ray photoelectron, and FT-IR spectroscopies, transmission electron and atomic force microscopies, zeta potential measurement, and Nile red fluorescence assay. They showed the tendencies to modulate the assembly of the proteins through different mechanisms. While GOQDs appeared to have the capacity to inhibit fibrillation, the presence of reduced GOQDs (rGOQDs) was found to promote protein assembly via shortening the nucleation phase, as suggested by ThT fluorescence data. Moreover, the structures produced in the presence of GOQDs or rGOQDs were totally nontoxic. We suggest that surface properties of these particles may be part of the differences in their mechanism (s) of action.

International Journal of Biological Macromolecules, Feb 1, 2018

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service... more This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

International Journal of Pharmaceutics, Dec 1, 2019

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Archives of Biochemistry and Biophysics, Dec 1, 2018

A growing body of evidence suggests that secretion and assembly of insulin to amyloid fibrils red... more A growing body of evidence suggests that secretion and assembly of insulin to amyloid fibrils reduce its efficacy in treating type II diabetes and may lead to dysfunctioning of several organs. The research presented here explores the effects of silibinin on the in vitro amyloid fibrillation and cytotoxicity of bovine insulin fibrils on SH-SY5Y human neuroblastoma cells. Interaction of the resulting structures with rat brain mitochondria was also investigated. Using a range of methods for amyloid detection we showed that insulin fibrillation was significantly inhibited by silibinin in a dose-dependent fashion. Moreover, we found that silibinin was very effective in attenuating insulin fibril-induced neuronal toxicity characterized by decrease of cell viability, the release of lactate dehydrogenase, intracellular reactive oxygen species enhancement, morphological alterations, and apoptotic cell death induction. While insulin fibrillation products showed the capacity to damage mitochondria, the resultant structures produced in the presence of silibinin were totally ineffective. Together, results demonstrate the capacity of insulin fibrils to cause SH-SY5Y cell death by inducing necrosis/apoptosis changes and suggest how silibinin may afford protection. It is concluded that elucidation of such protection may provide important insights into the development of preventive and therapeutic agents for amyloid-related diseases.

Biochimica Et Biophysica Acta - Biomembranes, Jun 1, 2020

Extensive research has shown that assembling of α-synuclein amyloid aggregates on mitochondria is... more Extensive research has shown that assembling of α-synuclein amyloid aggregates on mitochondria is an important mechanistic feature of Parkinson's disease (PD) and other Lewy body disorders. However, the molecular mechanism(s) of its neuronal toxicity remain unclear. Type 1 Hexokinase (HKI), a key enzyme in the control of brain glucose metabolism, plays an important role in protecting against mitochondrially-regulated apoptosis through reducing generation of reactive oxygen species (ROS). The release of mitochondrially-bound HKI causes a significant decrease in enzyme activity and triggers oxidative stress. Here, we have investigated the potency of amyloid fibrillation products arising from α-synuclein and hen egg white lysozyme (HEWL) for the release of HKI and ROS content enhancement in mitochondria isolated from rat brain. Results clearly indicate the capacity of the fibrillation products of α-synuclein, and not HEWL, to trigger release of HKI from the Type A binding site of mitochondria for the enzyme and to induce mitochondrial ROS enhancement in a dose-dependent manner. Moreover, we found that curcumin was very effective in preventing mitochondrial HKI release and ROS enhancement induced by α-synuclein fibrillation products. The pathophysiological significance of mitochondrial HKI activity and localization in pathogenesis of neurodegenerative disorders including PD are discussed. Taken together, these results may offer insight into a possible mechanism by which disease-related peptides and proteins may exert their neuronal toxicity.

Clinical Biochemistry, Sep 1, 2011

Introduction: Benzyl alcohol dehydrogenase able to convert benzyl alcohol to benzaldehyde has a r... more Introduction: Benzyl alcohol dehydrogenase able to convert benzyl alcohol to benzaldehyde has a role in toluene degradation pathway. In this research a recombinant benzyl alcohol dehydrogenase from R. ruber UKMP-5M was studied. R. ruber UKMP-5M was isolated from oil contaminated soils in Malaysia. Materials and methods: The toluene oxygenase activity from upper pathway was identified via Horseradish peroxidase (HRP) and indole. The catechol production from lower pathway was monitored with two enzyme catechol 1, 2 dioxygenase and catechol 2, 3 dioxygenase. The selected gene xylB was amplified with PCR at 64°C and cloned into E. coli expression system .The plasmid was digested with restriction enzymes NdeI and HindIII. The protein was expressed and it was purified by AKTA prime system. The results were analyzed with SDS-PAGE and Western blot. Results: R. ruber UKMP-5M was able to growth in 0.5 and 1 mM toluene. The toluene oxygenase activity was 0.173 U/ml and 0.054 U/ml for HRP and indole method was detected at 420 nm and 600 nm respectively. For catechol oxygenase was 0.020 U/ml and 0.028 U/ml at 260 and 375 nm. Benzyl alcohol dehydrogenase (xylB) was expressed at 25°C with 0.3 mM IPTG after 16 h. The recombinant protein was 38 kDa which was purified by Ni-NTA column with 400 mM imidazole. Conclusion: The presence of benzyl alcohol dehydrogenase which was encoded by xylB is required for toluene degradation pathway in R. ruber UKMP-5M.

Journal of Molecular Biology, Jun 1, 2011

Recent findings implicate that fibrillation products, the protein aggregates formed during the va... more Recent findings implicate that fibrillation products, the protein aggregates formed during the various steps leading to formation of mature fibrils, induce neurotoxicity predominantly in their intermediate oligomeric state. This has been shown to occur by increasing membrane permeability, eventually leading to cell death. Despite accumulating reports describing mechanisms of membrane permeabilization by oligomers in model membranes, studies directly targeted at characterizing the events occurring in biological membranes are rare. In the present report, we describe interaction of the original native structure, prefibrils and fibrils of hen egg white lysozyme (HEWL) with mitochondrial membranes, as an in vitro biological model, with the aim of gaining insight into possible mechanism of cytotoxicity at the membrane level. These structures were first characterized using a range of techniques, including fluorescence, size-exclusion chromatography, dynamic light scattering, transmission electron microscopy, dot blot analysis and circular dichroism. HEWL oligomers were found to be flexible/hydrophobic structures with the capacity to interact with mitochondrial membranes. Possible permeabilization of mitochondria was explored utilizing sensitive fluorometric and luminometric assays. Results presented demonstrate release of mitochondrial enzymes upon exposure to HEWL oligomers, but not native enzyme monomer or mature fibrils, in a concentration-dependent manner. Release of cytochrome c was also observed, as reported earlier, and membrane stabilization promoted by addition of calcium prevented release. Moreover, the oligomer-membrane interaction was influenced by high concentrations of NaCl and spermine. The observed release of proteins from mitochondria is suggested to occur by a nonspecific perturbation mechanism.

International Journal of Biological Macromolecules, Oct 1, 2013

Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disorder selectively... more Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disorder selectively affecting motor neurons; 90% of the total cases are sporadic, but 2% are associated with mutations in the gene coding for copper-zinc superoxide dismutase (SOD1). The causes of motor neuron death in ALS are poorly understood in general, but for SOD1-linked familial ALS (fALS), aberrant oligomerization of SOD1 mutant proteins has been strongly implicated. A growing body of evidence suggests that fALS-causing mutations destabilize the native structure of SOD1, leading to aberrant protein interactions for aggregation. In this work, we show that wild-type human SOD1 and two of its mutants (D101N, G72S) form amyloid like fibrils under destabilizing condition (in the presence of KSCN 0.2 M and DTT 50 mM) at 37 • C, pH 7.4. The formation of the aggregates was monitored by their ability to enhance the fluorescence of Thioflavin T (ThT) and their morphology was assessed by transmission electron microscopy (TEM). Furthermore, interaction of SOD1 aggregates with mitochondrial membrane of rat brain, as an in vitro biological model, with the aim of gaining an insight into possible mechanism of cytotoxicity at the membrane level was verified. Release of mitochondrial enzyme, malate dehydrogenase (MDH), upon exposure to SOD1 aggregates demonstrates that these aggregates could affect membrane permeability.

Journal of Applied Biotechnology Reports, Sep 1, 2017

International Journal of Biological Macromolecules, Oct 1, 2018

Effect of fibrillation conditions on the anti-amyloidogenic properties of polyphenols and their i... more Effect of fibrillation conditions on the anti-amyloidogenic properties of polyphenols and their involved mechanisms. Biomac (2018),

International Journal of Biological Macromolecules, Sep 1, 2015

An increasing number of studies conducted under in vitro and in vivo conditions, have concluded t... more An increasing number of studies conducted under in vitro and in vivo conditions, have concluded that polyphenols, compounds frequently occurring in many herbs with antioxidant properties, prevent and reverse amyloid fibril formation. However, the mechanisms by which these natural products modulate the protein aggregation process are poorly understood. Herein, a range of techniques including thioflavin T (ThT) and ANS fluorescence assays, electron microscopy and circular dichroism have been employed to determine the efficacy of rosmarinic acid (RA) and resveratrol (Res) on the inhibition/reversion of fibrillogenesis and hindering cytotoxicity induced by protofibrils and amyloid fibrils of hen egg white lysozyme (HEWL). Results demonstrated that both polyphenols effectively inhibit fibrillogenesis and destabilize preformed fibrils of HEWL in a concentration-dependent manner. Cytotoxicity protection on PC12 cells was also observed using the MTT assay, ROS production assay, and phase-contrast microscopy. It is suggested that the mechanism underlying the inhibitory effects of RA and Res is to prevent hydrophobic interactions between HEWL amyloidogenic prefibrillar species, although additional studies is needed to elucidate the detailed mechanisms involved. A combination of antioxidative and anti-amyloidogenic properties of these molecules may provide them with the described neuroprotective capacities.

Biomacromolecular Journal, Dec 1, 2016

The 25-35 fragment of the amyloid β(Aβ) peptide is a naturally occurring proteolytic by-product o... more The 25-35 fragment of the amyloid β(Aβ) peptide is a naturally occurring proteolytic by-product of its larger parent molecule that retains the amyloid characteristics and toxicity of the full length parent molecule. Aggregation of this peptide occurs rapidly in aqueous solutions and thus characterization of its folding process is very difficult. In the present study, early stages of Aβ(25-35) folding were observed in the presence of two mutations (N27A and M35A) in pure water, before and after exposure to pure dimethyl sulfoxide (DMSO) by conducting molecular dynamics simulations. Hydrophobic mutations decreased flexibility in the peptides structures, and peptide terminal mutation resulted in more compactness and beta secondary structure formation. Meanwhile, pure DMSO dramatically reduced the peptides dynamics, and pre-treatment with pure DMSO caused reduction and delay in beta structure formation in all studied peptides. It is concluded that the introduction of dimethyl sulfoxide and hydrophobic terminal M35A mutation could notably affect the folding of Aβ(25-35).

Plant Cell Tissue and Organ Culture, Jul 29, 2021

The changes in lipid peroxidation, H 2 O 2 , proline, protein and the involvement of the differen... more The changes in lipid peroxidation, H 2 O 2 , proline, protein and the involvement of the different antioxidant system (catalase, gayacoule peroxidase, ascorbate peroxidase) and callus-related traits were investigated in relation to salt stress in the callus of two different ploidy levels of Brassica including B. juncea and B. oleracea. The calluses of B. juncea genotypes were less sensitive to NaCl stress than that of B. oleraceae by increasing concentrations of NaCl from 0 to 200 mM.Tetraploid genotype (B. juncea cr3356) showed signi cant increase in the contents of protein and proline, and also activity of giacle peroxidase and catalase enzymes at higher salinity levels. Also, a signi cant decrease in the amount of H 2 O 2 and malondialdehyde occurred with increasing the salinity intensity. Diploid cultivar (B. oleracea bra 2828) had the lowest enzymatic activities and the highest content of H 2 O 2 and malondialdehyde with an increase in the salinity level. Therefore, this genotype was identi ed as the most sensitive cultivar to the salinity stress. The difference in the salinity resistance between diploid and amphidiploid species may be due to differences in the ploidy level of these species. This result suggests that tetraploid genome of B. oleraceae could be considered as a suitable candidate for production under salinity conditions by maintaining higher activities of antioxidant enzymes.

Biochimica Et Biophysica Acta - Biomembranes, Sep 1, 2012

Mitochondrial dysfunction is a common feature of many neurodegenerative disorders, although the r... more Mitochondrial dysfunction is a common feature of many neurodegenerative disorders, although the relative degree of this functional impairment and the mechanism of selective vulnerability in different regions of the brain related to various neurological diseases are not completely understood. In a recent study, we reported on brain mitochondrial membrane permeabilization upon interaction with hen egg white lysozyme (HEWL) protofibrils, and came to the conclusion that mitochondrial heterogeneity could offer an explanation for some of our observations. Accordingly, the first part of the present investigation was devoted on studies involving interaction of HEWL fibrillation products with mitochondria isolated from various areas of the brain, known to be affected in a number of well-characterized neurodegenerative conditions. This was followed by looking at heart and liver mitochondria. Membrane permeabilization was investigated by monitoring release of mitochondrial enzymes. Mitochondria isolated from cortex and hippocampus showed greater sensitivities than those prepared from substantia nigra. Results clearly demonstrate heterogeneity in brain mitochondria together with a higher resistance to permeabilization in these organelles in comparison with those isolated from liver and heart. Calcium and spermine were found to be more effective in preventing permeabilization in brain mitochondria, as compared to liver and heart. The structure-function aspects and physiological significance of the observations in relation to differences in composition, biophysical nature and morphological properties of mitochondria are discussed. It is argued that studies on heterogeneity in cellular membranes, the primary targets of toxic protofibrils, may provide important insights into mechanism of toxicity, with clinical and pathological manifestations.

ACS Chemical Neuroscience

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

Scientific Reports

The interplay between α-synuclein (α-syn) and catechols plays a central role in Parkinson’s disea... more The interplay between α-synuclein (α-syn) and catechols plays a central role in Parkinson’s disease. This may be related to the modulating effects of catechols on the various aspects of α-syn fibrillization. Some of these effects may be attributed to the membrane-binding properties of the protein. In this work, we compare the effect of some catechols, including dopamine, epinephrine, DOPAL, and levodopa in micromolar concentrations, on the in vitro cytotoxicity of α-syn fibrils on human neuroblastoma SH-SY5Y cells. The study was followed by comparing the interactions of resulting structures with rat brain mitochondria used as an in vitro biological model. The obtained results demonstrate that catechols-induced structures have lost their cytotoxicity mimicking apoptotic cell death mediated by α-syn aggregates in different proportions. Moreover, α-syn fibrils-induced mitochondrial dysfunction, evaluated by a range of biochemical assays, was modulated by catechols-modified α-syn oligom...

Journal of Molecular Biology

Parkinson's disease (PD) is the most common neurological movement disorder characterized by the s... more Parkinson's disease (PD) is the most common neurological movement disorder characterized by the selective and irreversible loss of dopaminergic neurons in substantia nigra pars compacta resulting in dopamine deficiency in the striatum. While most cases are sporadic or environmental, about 10% of patients have a positive family history with a genetic cause. The misfolding and aggregation of asynuclein (a-syn) as a casual factor in the pathogenesis of PD has been supported by a great deal of literature. Extensive studies of mechanisms underpinning degeneration of the dopaminergic neurons induced by a-syn dysfunction suggest a complex process that involves multiple pathways, including mitochondrial dysfunction and increased oxidative stress, impaired calcium homeostasis through membrane permeabilization, synaptic dysfunction, impairment of quality control systems, disruption of microtubule dynamics and axonal transport, endoplasmic reticulum/Golgi dysfunction, nucleus malfunction, and microglia activation leading to neuroinflammation. Among them mitochondrial dysfunction has been considered as the most primary target of a-syn-induced toxicity, leading to neuronal cell death in both sporadic and familial forms of PD. Despite reviewing many aspects of PD pathogenesis related to mitochondrial dysfunction, a systemic study on how a-syn malfunction/aggregation damages mitochondrial functionality and leads to neurodegeneration is missing in the literature. In this review, we give a detailed molecular overview of the proposed mechanisms by which a-syn, directly or indirectly, contributes to mitochondrial dysfunction. This may provide valuable insights for development of new therapeutic approaches in relation to PD. Antioxidant-based therapy as a potential strategy to protect mitochondria against oxidative damage, its challenges, and recent developments in the field are discussed.

Journal of Applied Biotechnology Reports, 2017

Background: Valerenic acid (VA) as a sesquiterpene constituent responsible for medicinal properti... more Background: Valerenic acid (VA) as a sesquiterpene constituent responsible for medicinal properties is derived from valeriana (Valeriana officinalis). It is well documented that the mutualistic basidiomycete Piriformospora indica substantially promotes secondary metabolites production. Nevertheless, our knowledge about molecular mechanism involved is rudimentary. Objective: In this study, we aimed to find the effect of P. indica cell wall extract (CWE) in modulation of transcriptional rate of sesquiterpene synthese (Sesqui-TPS). genes involved in VA biosynthesis in the host plant, V. officinalis. Material and Methods: Relative expression of putative terpene syntheses (VoTPS1, VoTPS3 and VoTPS7) genes was quantified by quantitative real time PCR (qRT-PCR) in the roots of valerian plants inoculated by two concentrations of the extract (2 and 4 % v/v) prepared from the cell wall of P. indica for various time intervals. As well as, VA content of roots of V. officinalis was measured. Res...