Influência do desequilíbrio redox sobre o metabolismo energético de eritrócitos falcêmicos
Carregando...
Data
2019-02-22
Autores
Chaves, Nayara Alves
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Estadual Paulista (Unesp)
Resumo
Os eritrócitos humanos são células únicas, altamente abundantes e uma das mais especializadas no organismo humano. A principal função dessas células consiste no transporte de oxigênio (O2) dos pulmões aos tecidos e o transporte de gás carbônico (CO2) dos tecidos aos pulmões por meio da molécula de hemoglobina (Hb). Apesar de relativamente estável, essa proteína pode se auto oxidar em metahemoglobina (MetHb) e gerar o radical superóxido (O2•-), o qual é um importante gatilho do processo oxidativo. Além de fontes endógenas, os eritrócitos são expostos a uma série de estressores ao longo da circulação. Apesar disso, a fim de prevenir ou atenuar o estresse oxidativo gerado, essas células são equipadas com um sistema antioxidante eficaz e autossustentável, intimamente relacionado com as vias da glicólise, das pentoses fosfato, da metahemoglobina redutase (MetHb redutase) e dos nucleotídeos, as quais contribuem para a manutenção do balanço redox e energético nos eritrócitos. Entretanto, algumas condições podem sobrecarregar esse mecanismo de defesa citado, como a anemia falciforme (AF). Sendo assim, o presente estudo objetivou avaliar biomarcadores do metabolismo redox, glicolítico, via das pentoses fosfato, via da metHb redutase e metabolismo de nucleotídeos, a fim de melhor compreender como as células falciformes lidam com a ruptura da homeostase metabólica, buscando marcadores de lesão oxidativa mais específicos para AF e novos e promissores antioxidantes para futuras investigações como terapia alternativa. Para isso, rigorosos critérios de exclusão foram adotados para obtenção dos grupos estudados, os quais foram compostos por 10 indivíduos sem hemoglobinopatias e 10 pacientes com AF. Imediatamente após a coleta, as amostras de sangue foram processadas para separação do plasma e preparação dos hemolisados específicos. Posteriormente, foram avaliados biomarcadores bioquímicos por métodos espectrofotométricos, cromatográficos e por imunomarcação. Diante disso, foi confirmado que os eritrócitos falciformes sobrecarregam o sistema de defesa antioxidante, levando a uma capacidade antioxidante deficiente que contribuiu significativamente para a hemólise. Dentre os antioxidantes avaliados, destaca-se a ergotioneína que apresentou redução de 2 vezes na AF, e correlações com os marcadores do metabolismo dos eritrócitos, configurando uma promissora alternativa terapêutica antioxidante para o tratamento da AF. Foi avaliado um marcador específico de oxidação de colesterol (ChAld) e, que também é um importante mediador de respostas inflamatórias, o qual apresentou níveis pelo menos duas vezes maiores nos pacientes. Finalmente, foi observado que as células falciformes parecem escapar ou de alguma forma alterar o mecanismo de deslocamento entre a glicólise e a via das pentoses fosfato bem descrita para eritrócitos saudáveis, mantendo ambas as vias reguladas positivamente.
Red blood cells (RBCs) are unique, highly specialized and the most abundant cells in the human organism. Their primary function is transportation of the respiratory gases, oxygen (O2) and carbon dioxide (CO2) between lungs and tissues through the hemoglobin (Hb). Although relatively stable, this protein can auto oxidize in methahemoglobin (MetHb) and generate the superoxide radical (O2 • -), which is an important trigger of the oxidative process. In addition to endogenous sources, erythrocytes are exposed to a number of stressors along the circulation. Despite this, in order to prevent or attenuate the oxidative stress generated, these cells are equipped with an effective and self-sustaining antioxidant system, closely related to the glycolysis, pentose phosphate pathway (PPP), metHb reductase pathway and nucleotide metabolism, which contribute to the maintenance of redox and energetic balance in erythrocytes. However, some conditions may overload this defense mechanism, such as sickle cell anemia (SCA). Thus, this study aimed to evaluate biomarkers of redox metabolism, glycolysis, PPP, metHb reductase pathway and nucleotide metabolism, in order to better understand how sickle cells deal with the rupture of metabolic homeostasis, seeking lesion markers more specific for SCA and promising antioxidants, for investigations as alternative therapy. For this, were adopted strict exclusion criteria to obtain the studied groups, which were composed of 10 individuals without hemoglobinopathies and 10 patients with SCA. Immediately after collection, the blood samples were processed for plasma separation and preparation of the specific hemolysates. Subsequently, biochemical biomarkers were evaluated by spectrophotometric, chromatographic and immunolabeling methods. In view of this, it was confirmed that sickle cells overloads the antioxidant defense system, leading to a deficient antioxidant capacity that contributed significantly to the hemolysis. Among the antioxidants evaluated, ergotionein showed a reduction of 2-fold in SCA, and correlations with markers of erythrocyte metabolism, forming a promising alternative antioxidant therapy for the treatment of SCA. A specific cholesterol oxidation marker (ChAld) was evaluated, which is also an important mediator of inflammatory responses, which presented at least two-fold higher levels in the patients. Finally, it has been observed that sickle cells appear to escape or otherwise alter the mechanism of displacement between glycolysis and the well described phosphate pentoses pathway for healthy erythrocytes, keeping both pathways up-regulated.
Red blood cells (RBCs) are unique, highly specialized and the most abundant cells in the human organism. Their primary function is transportation of the respiratory gases, oxygen (O2) and carbon dioxide (CO2) between lungs and tissues through the hemoglobin (Hb). Although relatively stable, this protein can auto oxidize in methahemoglobin (MetHb) and generate the superoxide radical (O2 • -), which is an important trigger of the oxidative process. In addition to endogenous sources, erythrocytes are exposed to a number of stressors along the circulation. Despite this, in order to prevent or attenuate the oxidative stress generated, these cells are equipped with an effective and self-sustaining antioxidant system, closely related to the glycolysis, pentose phosphate pathway (PPP), metHb reductase pathway and nucleotide metabolism, which contribute to the maintenance of redox and energetic balance in erythrocytes. However, some conditions may overload this defense mechanism, such as sickle cell anemia (SCA). Thus, this study aimed to evaluate biomarkers of redox metabolism, glycolysis, PPP, metHb reductase pathway and nucleotide metabolism, in order to better understand how sickle cells deal with the rupture of metabolic homeostasis, seeking lesion markers more specific for SCA and promising antioxidants, for investigations as alternative therapy. For this, were adopted strict exclusion criteria to obtain the studied groups, which were composed of 10 individuals without hemoglobinopathies and 10 patients with SCA. Immediately after collection, the blood samples were processed for plasma separation and preparation of the specific hemolysates. Subsequently, biochemical biomarkers were evaluated by spectrophotometric, chromatographic and immunolabeling methods. In view of this, it was confirmed that sickle cells overloads the antioxidant defense system, leading to a deficient antioxidant capacity that contributed significantly to the hemolysis. Among the antioxidants evaluated, ergotionein showed a reduction of 2-fold in SCA, and correlations with markers of erythrocyte metabolism, forming a promising alternative antioxidant therapy for the treatment of SCA. A specific cholesterol oxidation marker (ChAld) was evaluated, which is also an important mediator of inflammatory responses, which presented at least two-fold higher levels in the patients. Finally, it has been observed that sickle cells appear to escape or otherwise alter the mechanism of displacement between glycolysis and the well described phosphate pentoses pathway for healthy erythrocytes, keeping both pathways up-regulated.
Descrição
Palavras-chave
Metabolismo eritrocitário, Hemoglobina S, Capacidade antioxidante, Erythrocyte metabolism, Hemoglobin S, Antioxidant capacity