14 results on '"Erustes, Adolfo Garcia"'
Search Results
2. Cannabidiol Recovers Dopaminergic Neuronal Damage Induced by Reserpine or α-synuclein in Caenorhabditis elegans
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da Cruz Guedes, Erika, Erustes, Adolfo Garcia, Leão, Anderson H. F. F., Carneiro, César Alves, Abílio, Vanessa C., Zuardi, Antonio W., Hallak, Jaime Eduardo C., Crippa, José Alexandre, Bincoletto, Claudia, Smaili, Soraya S., Reckziegel, Patrícia, and Pereira, Gustavo J. S.
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- 2023
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3. Artemisia vulgaris Induces Tumor-Selective Ferroptosis and Necroptosis via Lysosomal Ca2+ Signaling.
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Zamarioli, Lucas dos Santos, Santos, Michele Rosana Maia, Erustes, Adolfo Garcia, Meccatti, Vanessa Marques, Pereira, Thaís Cristine, Smaili, Soraya S., Marcucci, Maria Cristina, Oliveira, Carlos Rocha, Pereira, Gustavo J. S., and Bincoletto, Claudia
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CANCER chemotherapy ,ORGANIC compound analysis ,CHINESE medicine ,LYSOSOMES ,IN vitro studies ,LIQUID chromatography-mass spectrometry ,RESEARCH funding ,BREAST tumors ,WORMWOOD ,CALCIUM-binding proteins ,APOPTOSIS ,NECROSIS ,CHRONIC myeloid leukemia ,CELLULAR signal transduction ,PHYTOCHEMICALS ,DESCRIPTIVE statistics ,FIBROBLASTS ,PLANT extracts ,CELL lines ,CELL death ,ORGANIC compounds ,CELL survival ,DATA analysis software - Abstract
Objective: To evaluate the chemical composition and effects of Artemisia vulgaris (AV) hydroalcoholic extract (HEAV) on breast cancer cells (MCF-7 and SKBR-3), chronic myeloid leukemia (K562) and NIH/3T3 fibroblasts. Methods: Phytochemical analysis of HEAV was done by high-performance liquid chromatography-mass (HPLC) spectrometry. Viability and cell death studies were performed using trypan blue and Annexin/FITC-7AAD, respectively. Ferrostatin-1 (Fer-1) and necrostatin-1 (Nec-1) were used to assess the mode of HEAV-induced cell death and acetoxymethylester (BAPTA-AM) was used to verify the involvement of cytosolic calcium in this event. Cytosolic calcium measurements were made using Fura-2-AM. Results: HEAV decreased the viability of MCF-7, SKBR-3 and K562 cells (P<0.05). The viability of HEAV-treated K562 cells was reduced compared to HEAV-exposed fibroblasts (P<0.05). Treatment of K562 cells with HEAV induced cell death primarily by late apoptosis and necrosis in assays using annexin V-FITC/7-AAD (P<0.05). The use of Nec-1 and Fer-1 increased the viability of K562 cells treated with HEAV relative to cells exposed to HEAV alone (P<0.01). HEAV-induced Ca
2+ release mainly from lysosomes in K562 cells (P<0.01). Furthermore, BAPTA-AM, an intracellular Ca2+ chelator, decreased the number of non-viable cells treated with HEAV (P<0.05). Conclusions: HEAV is cytotoxic and activates several modalities of cell death, which are partially dependent on lysosomal release of Ca2+ . These effects may be related to artemisinin and caffeoylquinic acids, the main compounds identified in HEAV. [ABSTRACT FROM AUTHOR]- Published
- 2024
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4. Autophagy and intermittent fasting: the connection for cancer therapy?
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Antunes, Fernanda, Erustes, Adolfo Garcia, Costa, Angélica Jardim, Nascimento, Ana Carolina, Bincoletto, Claudia, Ureshino, Rodrigo Portes, Pereira, Gustavo José Silva, and Smaili, Soraya Soubhi
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- 2018
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5. NAADP-Evoked Ca 2+ Signaling Leads to Mutant Huntingtin Aggregation and Autophagy Impairment in Murine Astrocytes.
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Pereira, Cássia Arruda de Souza, Medaglia, Natalia de Castro, Ureshino, Rodrigo Portes, Bincoletto, Claudia, Antonioli, Manuela, Fimia, Gian Maria, Piacentini, Mauro, Pereira, Gustavo José da Silva, Erustes, Adolfo Garcia, and Smaili, Soraya Soubhi
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CALCIUM ions ,HUNTINGTON disease ,AUTOPHAGY ,TRINUCLEOTIDE repeats ,NIACIN ,HOMEOSTASIS ,CHELATING agents - Abstract
Huntington's disease (HD) is a progressive neurodegenerative disease characterized by mutations in the huntingtin gene (mHtt), causing an unstable repeat of the CAG trinucleotide, leading to abnormal long repeats of polyglutamine (poly-Q) in the N-terminal region of the huntingtin, which form abnormal conformations and aggregates. Alterations in Ca
2+ signaling are involved in HD models and the accumulation of mutated huntingtin interferes with Ca2+ homeostasis. Lysosomes are intracellular Ca2+ storages that participate in endocytic and lysosomal degradation processes, including autophagy. Nicotinic acid adenine dinucleotide phosphate (NAADP) is an intracellular second messenger that promotes Ca2+ release from the endo-lysosomal system via Two-Pore Channels (TPCs) activation. Herein, we show the impact of lysosomal Ca2+ signals on mHtt aggregation and autophagy blockade in murine astrocytes overexpressing mHtt-Q74. We observed that mHtt-Q74 overexpression causes an increase in NAADP-evoked Ca2+ signals and mHtt aggregation, which was inhibited in the presence of Ned-19, a TPC antagonist, or BAPTA-AM, a Ca2+ chelator. Additionally, TPC2 silencing revert the mHtt aggregation. Furthermore, mHtt has been shown co-localized with TPC2 which may contribute to its effects on lysosomal homeostasis. Moreover, NAADP-mediated autophagy was also blocked since its function is dependent on lysosomal functionality. Taken together, our data show that increased levels of cytosolic Ca2+ mediated by NAADP causes mHtt aggregation. Additionally, mHtt co-localizes with the lysosomes, where it possibly affects organelle functions and impairs autophagy. [ABSTRACT FROM AUTHOR]- Published
- 2023
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6. α-Synuclein Interactions in Mitochondria-ER Contacts: A Possible Role in Parkinson's Disease.
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Erustes, Adolfo Garcia, Guarache, Gabriel Cicolin, Guedes, Erika da Cruz, Leão, Anderson Henrique França Figueredo, Pereira, Gustavo José da Silva, and Smaili, Soraya Soubhi
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PARKINSON'S disease , *ALPHA-synuclein , *ALZHEIMER'S disease , *AMYOTROPHIC lateral sclerosis , *PATHOLOGY - Abstract
Endoplasmic reticulum-mitochondria contact sites regulate various biological processes, such as mitochondrial dynamics, calcium homeostasis, autophagy and lipid metabolism. Notably, dysfunctions in these contact sites are closely related to neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. However, details about the role of endoplasmic reticulum-mitochondria contact sites in neurodegenerative diseases remain unknown. In Parkinson's disease, interactions between α-synuclein in the contact sites and components of tether complexes that connect organelles can lead to various dysfunctions, especially with regards to calcium homeostasis. This review will summarize the main tether complexes present in endoplasmic reticulum-mitochondria contact sites, and their roles in calcium homeostasis and trafficking. We will discuss the impact of α-synuclein accumulation, its interaction with tethering complex components and the implications in Parkinson's disease pathology. [ABSTRACT FROM AUTHOR]
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- 2022
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7. Overexpression of α‐synuclein inhibits mitochondrial Ca2+ trafficking between the endoplasmic reticulum and mitochondria through MAMs by altering the GRP75–IP3R interaction.
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Erustes, Adolfo Garcia, D'Eletto, Manuela, Guarache, Gabriel Cicolin, Ureshino, Rodrigo Portes, Bincoletto, Claudia, da Silva Pereira, Gustavo José, Piacentini, Mauro, and Smaili, Soraya Soubhi
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- 2021
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8. Effects of Aging in the Striatum and Substantia Nigra of a Parkinson's Disease Animal Model.
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Ureshino, Rodrigo Portes, Costa, Angelica Jardim, Erustes, Adolfo Garcia, Pereira, Gustavo Jose da Silva, Sinigaglia-Coimbra, Rita, and Smaili, Soraya Soubhi
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PARKINSON'S disease ,LIPOFUSCINS ,ROTENONE - Abstract
Aging is a multifactorial process associated with functional deficits, and the brain is more prone to developing chronic degenerative diseases such as Parkinson's disease. Several groups have tried to correlate the age-related ultrastructural alterations to the neurodegeneration process using in vivo pharmacological models, but due to the limitations of the animal models, particularly in aged animals, the results are difficult to interpret. In this work, we investigated neurodegeneration induced by rotenone, as a pharmacological model of Parkinson's disease, in both young and aged Wistar rats. We assessed animal mobility, tyrosine hydroxylase staining in the substantia nigra pars compacta (SNpc), and TdT-mediated dUTP-biotin nick end labeling-positive nuclei and reactive oxygen species production in the striatum. Interestingly, the mobility impairment, dopaminergic neuron loss, and elevated number of apoptotic nuclei in the striatum of aged control rats were similar to young rotenone-treated animals. Moreover, we observed many ultrastructural alterations, such as swollen mitochondria in the striatum, and massive lipofuscin deposits in the SNpc of the aged rotenone-treated animals. We conclude that the rotenone model can be employed to explore age-related alterations in the ontogeny that can increase vulnerability in the striatum and SNpc, which may contribute to Parkinson's disease pathogenesis. [ABSTRACT FROM AUTHOR]
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- 2018
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9. Overexpression of α-synuclein in an astrocyte cell line promotes autophagy inhibition and apoptosis.
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Erustes, Adolfo Garcia, Stefani, Fernanda Yakel, Terashima, Juliana Yoshie, Stilhano, Roberta Sessa, Monteforte, Priscila Totarelli, da Silva Pereira, Gustavo José, Han, Sang Won, Calgarotto, Andrana Karla, Hsu, Yi‐Te, Ureshino, Rodrigo Portes, Bincoletto, Cláudia, and Smaili, Soraya Soubhi
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- 2018
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10. Reduction in skeletal muscle fibrosis of spontaneously hypertensive rats after laceration by microRNA targeting angiotensin II receptor.
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Stilhano, Roberta Sessa, Samoto, Vivian Yochiko, Silva, Leonardo Martins, Pereira, Gustavo José, Erustes, Adolfo Garcia, Smaili, Soraya Soubhi, and Won Han, Sang
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SKELETAL muscle ,ANGIOTENSIN receptors ,MICRORNA ,LABORATORY rats ,GENE expression ,POLYMERASE chain reaction - Abstract
Regeneration of injured skeletal muscles is affected by fibrosis, which can be improved by the administration of angiotensin II (AngII) receptor (ATR) blockers in normotensive animals. However, the role of ATR in skeletal muscle fibrosis in hypertensive organisms has not been investigated yet. The tibialis anterior (TA) muscle of spontaneously hypertensive (SHR) and Wistar rats (WR) were lacerated and a lentivector encoding a microRNA targeting AngII receptor type 1 (At1) (Lv-mirAT1a) or control (Lv-mirCTL) was injected. The TA muscles were collected after 30 days to evaluate fibrosis by histology and gene expression by real-time quantitative PCR (RT-qPCR) and Western blot. SHR’s myoblasts were analyzed by RT-qPCR, 48 h after transduction. In the SHR’s TA, AT1 protein expression was 23.5-fold higher than in WR without injury, but no difference was observed in the angiotensin II receptor type 2 (AT2) protein expression. TA laceration followed by suture (LS) produced fibrosis in the SHR (23.3±8.5%) and WR (7.9±1.5%). Lv-mirAT1 treatment decreased At1 gene expression in 50% and reduced fibrosis to 7% 30 days after. RT-qPCR showed that reduction in At1 expression is due to downregulation of the At1a but not of the At1b. RT-qPCR of myoblasts from SHR transduced with Lv-mirAT1a showed downregulation of the Tgf-b1, Tgf-b2, Smad3, Col1a1, and Col3a1 genes by mirAT1a. In vivo and in vitro studies indicate that hypertension overproduces skeletal muscle fibrosis, and AngII-AT1a signaling is the main pathway of fibrosis in SHR. Moreover, muscle fibrosis can be treated specifically by in loco injection of Lv-mirAT1a without affecting other organs. [ABSTRACT FROM AUTHOR]
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- 2017
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11. Pharmacological Modulators of Autophagy as a Potential Strategy for the Treatment of COVID-19.
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Pereira, Gustavo José da Silva, Leão, Anderson Henrique França Figueredo, Erustes, Adolfo Garcia, Morais, Ingrid Beatriz de Melo, Vrechi, Talita Aparecida de Moraes, Zamarioli, Lucas dos Santos, Pereira, Cássia Arruda Souza, Marchioro, Laís de Oliveira, Sperandio, Letícia Paulino, Lins, Ísis Valeska Freire, Piacentini, Mauro, Fimia, Gian Maria, Reckziegel, Patrícia, Smaili, Soraya Soubhi, and Bincoletto, Claudia
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COVID-19 treatment ,HEPARIN ,GLUCOCORTICOIDS ,AUTOPHAGY ,TEICOPLANIN ,ACE inhibitors ,COVID-19 ,VIRUS diseases - Abstract
The family of coronaviruses (CoVs) uses the autophagy machinery of host cells to promote their growth and replication; thus, this process stands out as a potential target to combat COVID-19. Considering the different roles of autophagy during viral infection, including SARS-CoV-2 infection, in this review, we discuss several clinically used drugs that have effects at different stages of autophagy. Among them, we mention (1) lysosomotropic agents, which can prevent CoVs infection by alkalinizing the acid pH in the endolysosomal system, such as chloroquine and hydroxychloroquine, azithromycin, artemisinins, two-pore channel modulators and imatinib; (2) protease inhibitors that can inhibit the proteolytic cleavage of the spike CoVs protein, which is necessary for viral entry into host cells, such as camostat mesylate, lopinavir, umifenovir and teicoplanin and (3) modulators of PI3K/AKT/mTOR signaling pathways, such as rapamycin, heparin, glucocorticoids, angiotensin-converting enzyme inhibitors (IECAs) and cannabidiol. Thus, this review aims to highlight and discuss autophagy-related drugs for COVID-19, from in vitro to in vivo studies. We identified specific compounds that may modulate autophagy and exhibit antiviral properties. We hope that research initiatives and efforts will identify novel or "off-label" drugs that can be used to effectively treat patients infected with SARS-CoV-2, reducing the risk of mortality. [ABSTRACT FROM AUTHOR]
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- 2021
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12. Lack of Autophagy Induction by Lithium Decreases Neuroprotective Effects in the Striatum of Aged Rats.
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Costa, Angelica Jardim, Erustes, Adolfo Garcia, Sinigaglia, Rita, Girardi, Carlos Eduardo Neves, Pereira, Gustavo José da Silva, Ureshino, Rodrigo Portes, Smaili, Soraya Soubhi, and Sidorova, Yulia
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NEUROPROTECTIVE agents , *AUTOPHAGY , *CELL survival , *REACTIVE oxygen species , *LYSOSOMES , *OXYGEN consumption - Abstract
The pharmacological modulation of autophagy is considered a promising neuroprotective strategy. While it has been postulated that lithium regulates this cellular process, the age-related effects have not been fully elucidated. Here, we evaluated lithium-mediated neuroprotective effects in young and aged striatum. After determining the optimal experimental conditions for inducing autophagy in loco with lithium carbonate (Li2CO3), we measured cell viability, reactive oxygen species (ROS) generation and oxygen consumption with rat brain striatal slices from young and aged animals. In the young striatum, Li2CO3 increased tissue viability and decreased ROS generation. These positive effects were accompanied by enhanced levels of LC3-II, LAMP 1, Ambra 1 and Beclin-1 expression. In the aged striatum, Li2CO3 reduced the autophagic flux and increased the basal oxygen consumption rate. Ultrastructural changes in the striatum of aged rats that consumed Li2CO3 for 30 days included electrondense mitochondria with disarranged cristae and reduced normal mitochondria and lysosomes area. Our data show that the striatum from younger animals benefits from lithium-mediated neuroprotection, while the striatum of older rats does not. These findings should be considered when developing neuroprotective strategies involving the induction of autophagy in aging. [ABSTRACT FROM AUTHOR]
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- 2021
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13. The Interplay between Ca2+ Signaling Pathways and Neurodegeneration.
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Ureshino, Rodrigo Portes, Erustes, Adolfo Garcia, Bassani, Taysa Bervian, Wachilewski, Patrícia, Guarache, Gabriel Cicolin, Nascimento, Ana Carolina, Costa, Angelica Jardim, Smaili, Soraya Soubhi, and da Silva Pereira, Gustavo José
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LYSOSOMES , *CENTRAL nervous system , *ENDOPLASMIC reticulum , *NEURODEGENERATION , *LIPASES , *BLOOD flow , *DISEASE progression , *HUNTINGTIN protein - Abstract
Calcium (Ca2+) homeostasis is essential for cell maintenance since this ion participates in many physiological processes. For example, the spatial and temporal organization of Ca2+ signaling in the central nervous system is fundamental for neurotransmission, where local changes in cytosolic Ca2+ concentration are needed to transmit information from neuron to neuron, between neurons and glia, and even regulating local blood flow according to the required activity. However, under pathological conditions, Ca2+ homeostasis is altered, with increased cytoplasmic Ca2+ concentrations leading to the activation of proteases, lipases, and nucleases. This review aimed to highlight the role of Ca2+ signaling in neurodegenerative disease-related apoptosis, where the regulation of intracellular Ca2+ homeostasis depends on coordinated interactions between the endoplasmic reticulum, mitochondria, and lysosomes, as well as specific transport mechanisms. In neurodegenerative diseases, alterations-increased oxidative stress, energy metabolism alterations, and protein aggregation have been identified. The aggregation of α-synuclein, β-amyloid peptide (Aβ), and huntingtin all adversely affect Ca2+ homeostasis. Due to the mounting evidence for the relevance of Ca2+ signaling in neuroprotection, we would focus on the expression and function of Ca2+ signaling-related proteins, in terms of the effects on autophagy regulation and the onset and progression of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]
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- 2019
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14. Overexpression of α-synuclein inhibits mitochondrial Ca 2+ trafficking between the endoplasmic reticulum and mitochondria through MAMs by altering the GRP75-IP3R interaction.
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Erustes AG, D'Eletto M, Guarache GC, Ureshino RP, Bincoletto C, da Silva Pereira GJ, Piacentini M, and Smaili SS
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- Endoplasmic Reticulum metabolism, HEK293 Cells, HSP70 Heat-Shock Proteins, Humans, Membrane Proteins, Mitochondria metabolism, Calcium metabolism, alpha-Synuclein metabolism
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Mitochondria-associated ER membranes (MAMs) are formed by close and specific components in the contact sites between the endoplasmic reticulum (ER) and mitochondria, which participate in several cell functions, including lipid metabolism, autophagy, and Ca
2+ signaling. Particularly, the presence of α-synuclein (α-syn) in MAMs was previously demonstrated, indicating a physical interaction among some proteins in this region and a potential involvement in cell dysfunctions. MAMs alterations are associated with neurodegenerative diseases such as Parkinson's disease (PD) and contribute to the pathogenesis features. Here, we investigated the effects of α-syn on MAMs and Ca2+ transfer from the ER to mitochondria in WT- and A30P α-syn-overexpressing SH-SY5Y or HEK293 cells. We observed that α-syn potentiates the mitochondrial membrane potential (Δψm ) loss induced by rotenone, increases mitophagy and mitochondrial Ca2+ overload. Additionally, in α-syn-overexpressing cells, we found a reduction in ER-mitochondria contact sites through the impairment of the GRP75-IP3R interaction, however, with no alteration in VDAC1-GRP75 interaction. Consequently, after Ca2+ release from the ER, α-syn-overexpressing cells demonstrated a reduction in Ca2+ buffering by mitochondria, suggesting a deregulation in MAM activity. Taken together, our data highlight the importance of the α-syn/MAMs/Ca2+ axis that potentially affects cell functions in PD., (© 2021 Wiley Periodicals LLC.)- Published
- 2021
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