Alarcón-Aguilar Adriana, Luna-López Armando, Ventura-Gallegos José L, Lazzarini Roberto, Galván-Arzate Sonia, González-Puertos Viridiana Y, Morán Julio, Santamaría Abel, Königsberg Mina
Departamento de Ciencias de la Salud, DCBS, Universidad Autónoma Metropolitana Iztapalapa, ciudad de México, México.
Area de Ciencia Básica, Instituto Nacional de Geriatría, SSA, ciudad de México, Mexico.
Neurobiol Aging. 2014 Aug;35(8):1901-12. doi: 10.1016/j.neurobiolaging.2014.01.143. Epub 2014 Feb 7.
Astrocytes are key players for brain physiology, protecting neurons by releasing antioxidant enzymes; however, they are also susceptible to damage by neurotoxins. Nuclear factor erythroid-derived 2-like 2 (Nrf2) is a central regulator of the antioxidant response, and therefore, pharmacologic inducers are often used to activate this transcription factor to induce cellular protection. To date, it still remains unknown if cells from aged animals are capable of developing this response. Therefore, the purpose of this work was to determine if cortical astrocytes derived from old rats are able to respond to tertbuthyl-hydroquinene (tBHQ) pretreatment and stimulate the Nrf2-antioxidant response pathway to induce an antioxidant strategy against MPP+ toxicity, one of the most used molecules to model Parkinson's disease. Our results show that, although astrocytes from adult and old rats were more susceptible to MPP+ toxicity than astrocytes from newborn rats, when pretreated with tertbuthyl-hydroquinene, they were able to transactivate Nrf2, increasing antioxidant enzymes and developing cellular protection. These results are discussed in terms of the doses used to create protective responses.
星形胶质细胞是脑生理学的关键参与者,通过释放抗氧化酶来保护神经元;然而,它们也容易受到神经毒素的损害。核因子红细胞衍生2样2(Nrf2)是抗氧化反应的核心调节因子,因此,药物诱导剂常被用于激活该转录因子以诱导细胞保护。迄今为止,老龄动物的细胞是否能够产生这种反应仍不清楚。因此,本研究的目的是确定源自老年大鼠的皮质星形胶质细胞是否能够对叔丁基对苯二酚(tBHQ)预处理作出反应,并刺激Nrf2-抗氧化反应途径,以诱导针对MPP +毒性的抗氧化策略,MPP +是用于模拟帕金森病的最常用分子之一。我们的结果表明,尽管成年和老年大鼠的星形胶质细胞比新生大鼠的星形胶质细胞对MPP +毒性更敏感,但在用叔丁基对苯二酚预处理后,它们能够反式激活Nrf2,增加抗氧化酶并产生细胞保护作用。根据用于产生保护反应的剂量对这些结果进行了讨论。