Navegando por Autor "Silva, Alessandra Oliveira"

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Epigenetic regulation of the N-terminal truncated isoform of matrix metalloproteinase-2 (NTT-MMP-2) and Its presence in renal and cardiac diseases.
(2021) Cruz, Juliana de Oliveira; Silva, Alessandra Oliveira; Ribeiro, Jessyca Milene; Luizon, Marcelo Rizzatti; Ceron, Carla Speroni
Several clinical and experimental studies have documented a compelling and critical role for the full-length matrix metalloproteinase-2 (FL-MMP-2) in ischemic renal injury, progressive renal fibrosis, and diabetic nephropathy. A novel N-terminal truncated isoform of MMP-2 (NTT-MMP-2) was recently discovered, which is induced by hypoxia and oxidative stress by the activation of a latent promoter located in the first intron of the MMP2 gene. This NTT-MMP-2 isoform is enzymatically active but remains intracellular in or near the mitochondria. In this perspective article, we first present the findings about the discovery of the NTT-MMP-2 isoform, and its functional and structural differences as compared with the FL-MMP-2 isoform. Based on publicly available epigenomics data from the Encyclopedia of DNA Elements (ENCODE) project, we provide insights into the epigenetic regulation of the latent promoter located in the first intron of the MMP2 gene, which support the activation of the NTT-MMP-2 isoform. We then focus on its functional assessment by covering the alterations found in the kidney of transgenic mice expressing the NTT-MMP-2 isoform. Next, we highlight recent findings regarding the presence of the NTT-MMP-2 isoform in renal dysfunction, in kidney and cardiac diseases, including damage observed in aging, acute ischemia-reperfusion injury (IRI), chronic kidney disease, diabetic nephropathy, and human renal transplants with delayed graft function. Finally, we briefly discuss how our insights may guide further experimental and clinical studies that are needed to elucidate the underlying mechanisms and the role of the NTT-MMP-2 isoform in renal dysfunction, which may help to establish it as a potential therapeutic target in kidney diseases.
Ethanol consumption and sepsis : mechanisms of organ damage.
(2021) Silva, Alessandra Oliveira; Prohaska, Clare C.; Ceron, Carla Speroni
Sepsis is highly prevalent, and is one of the main causes of mortality among hospitalized patients. Ethanol consumption in large quantities compromises the normal functioning of the body, leading to dysfunction of multiple different organ systems. The association between sepsis and ethanol is not fully understood, but it is well accepted that ethanol consumption plays a role in the development of sepsis. Both sepsis and ethanol cause inflammatory dysfunction and promote oxidative stress. Antioxidant agents may be highly relevant targets to abrogate the effects of sepsis in patients who also consume large amounts of ethanol. This review focuses on presenting the main mechanisms involved between sepsis and ethanol consumption, and to describe the main antioxidants that have been used as therapeutic agents.
Nicotine exposure through breastfeeding affects brainderived neurotrophic factor and synaptic proteins levels in the brain of stressed adult female mice.
(2022) Pereira Júnior, Antonio Alves; Amorim, Gabriel Estevam Santos de; Garcia, Raphael Caio Tamborelli; Ribeiro, Jessyca Milene; Silva, Alessandra Oliveira; Almeida, Carolina Aparecida de Faria; Ceron, Carla Speroni; Ruginsk, Silvia Graciela; Rodrigues, José Antunes; Elias, Lucila Leico Kagohara; Dias, Marcos Vinícios Salles; Marcourakis, Tania; Torres, Larissa Helena
Nicotine has been used during pregnancy and lactation as a tobacco harm reduction strategy. However, it is unclear whether nicotine exposure during a critical development period negatively impacts stress responses in adulthood. This study investigated how nicotine, administered via breastfeeding, affects the brain-derived neurotrophic factor (BDNF), synaptic proteins levels, and anxiety-like behavior in adult female mice subjected to stress. Female Swiss mice were exposed to saline or nicotine (8 mg/kg/day) through breastfeeding between their fourth and 17th postnatal days (P) via implanted osmotic mini pumps. The unpredictable chronic mild stress (UCMS) protocol was performed during their adulthood (P65) for 10 consecutive days, followed by the elevated plus maze (EPM) test 1 day after the protocol. Animals were euthanized and their blood, collected for plasma corticosterone measurements and their brain structures, dissected for BDNF and synaptic proteins analyses. We found no significant differences in corticosterone levels between groups (Saline/Nonstress, Nicotine/Non-stress, Saline/Stress, and Nicotine/Stress). The UCMS protocol hindered weight gain. Mice exposed to nicotine through breastfeeding with or without the UCMS protocol in adulthood showed higher grooming and head dipping frequency; decreased BDNF levels in cerebellum and striatum; increased postsynaptic density protein 95 (PSD-95), synapsin I, and synaptophysin levels in cerebellum; and decreased PSD-95 and synapsin I levels in brainstem. Our results indicate that nicotine exposure through breastfeeding leads to long-lasting behavioral effects and synaptic protein changes, most of which were independent of the UCMS protocol, even after a long nicotine-free period, highlighting the importance of further studies on nicotine exposure during development.
Protective effects of kefir against unpredictable chronic stress alterations in mice central nervous system, heart, and kidney.
(2022) Silva, Alessandra Oliveira; Ribeiro, Jessyca Milene; Patrocínio, Talita Bárbara; Amorim, Gabriel Estevam Santos de; Pereira Júnior, Antônio Alves; Angelo, Marilene Lopes; Paula, Fernanda Borges de Araújo; Oliveira, Nelma de Mello Silva; Ruginsk, Silvia Graciela; Rodrigues, José Antunes; Elias, Lucila Leico Kagohara; Dias, Marcos Vinícios Salles; Torres, Larissa Helena; Ceron, Carla Speroni
Kefir is a probiotic mixture with anxiolytic and antioxidant properties. Chronic stress can lead to anxiety disorders and increase oxidative damage in organs such as the heart and kidney. In this study, we examined whether kefir ameliorates the anxiety-like behavior of mice submitted to chronic unpredictable stress (CUS) by modulating brain-derived neurotrophic factor (BDNF) and corticosterone levels and whether kefir modifies the oxidative parameters in the heart and kidney of mice. Male Swiss mice received kefir (0.3 mL/100 g/day) or milk for 30 days (gavage). On the 10th day, the mice were submitted to CUS. Behavioral analysis was performed using the elevated plus maze and forced swimming tests. BDNF levels were analyzed in brain tissues. Heart and kidney superoxide dismutase (SOD), catalase, glutathione (GSH), thiobarbituric acid reactive substances (TBARS), 3-nitrotyrosine, metalloproteinase-2 (MMP-2), and plasma corticosterone were evaluated. Kefir reverted the CUS-induced decrease in the time spent in the open arms, the increase in grooming frequency, and decrease in the head dipping frequency, but not the reduced immobility time. CUS decreased the cerebellum BDNF levels and increased corticosterone levels, which were restored by Kefir. Neither catalase and SOD activities nor GSH, TBARS, 3-nitrotyrosine, and MMP-2 were modified by CUS in the heart. In the kidney, CUS increased 3-nitrotyrosine and MMP-2. Kefir increased the antioxidant defense in the heart and kidney of control and CUS mice. These results suggest that kefir ameliorated CUS-induced anxiety-like behavior by modulating brain BDNF and corticosterone levels. Kefir also increased the antioxidant defense of mice heart and kidney.