Department of Agricultural Biotechnology, Faculty of Agriculture and Natural Sciences, Duzce University, 81620, Duzce, Turkey.
Department of Molecular Biology and Genetics, Faculty of Arts and Sciences, Bingol University, 12000, Bingöl, Turkey.
Neurochem Res. 2020 Oct;45(10):2385-2397. doi: 10.1007/s11064-020-03097-w. Epub 2020 Jul 25.
Diabetes mellitus is a prevalent metabolic disorder associated with multiple complications including neuropathy, memory loss and cognitive decline. Despite a long history of studies on diabetic complications, there are no effective therapeutic strategies for neuroprotection in diabetes. Hyperglycemia-induced imbalance in programmed cell death could initiate a decline in neural tissue cells viability. Various nanomaterials can induce either cell death or cell survival dependent on the type and surface features. Pristine C fullerene is a nontoxic nanomaterial, which exhibits antioxidant and cytoprotective properties. However, the precise molecular mechanism with which the C nanoparticle exerts cytoprotective effect in diabetic subjects has not yet been fully addressed. Thus, this study aimed to determine whether C fullerene prevents oxidative stress impairment and to explore the effects of C fullerene on apoptosis and autophagy in diabetes mellitus to clarify its potential mechanisms. These effects have been examined for olive oil extracted C fullerene on the hippocampus of STZ diabetic rats. Up-regulation of Caspase-3, Beclin-1 and oxidative stress indexes and down-regulation of Bcl-2 were observed in the brain of STZ-diabetic rats. The exposure to C fullerene for a period of 12 weeks ameliorate redox imbalance, hyperglycemia-induced disturbances in apoptosis and autophagy flux via modulation of Caspase-3, Bcl-2, Beclin-1 and LC3I/II contents. Furthermore, C fullerene ameliorated the LC3I/II ratio and prevented extremely increased autophagy flux. Contrarily, pristine C fullerene had no modulatory effect on all studied apoptotic and autophagy markers in non-diabetic groups. Therefore, oil extracted C fullerene exhibits cytoprotective effect in hyperglycemia-stressed hippocampal cells. The presented results confirm that pristine C fullerene nanoparticles can protect hippocampal cells against hyperglycemic stress via anti-oxidant, anti-apoptotic effects and amelioration of autophagy flux. Moreover, C fullerene regulates a balance of autophagy via BCL-2/Beclin-1 reciprocal expression that could prevent functional disturbances in hippocampus.
糖尿病是一种常见的代谢紊乱疾病，与多种并发症有关，包括神经病变、记忆丧失和认知能力下降。尽管对糖尿病并发症进行了长期的研究，但目前仍没有有效的神经保护治疗策略。高血糖诱导的程序性细胞死亡失衡可能导致神经组织细胞活力下降。各种纳米材料可以根据类型和表面特征诱导细胞死亡或细胞存活。纯净的 C 富勒烯是一种无毒的纳米材料，具有抗氧化和细胞保护特性。然而，C 纳米颗粒在糖尿病患者中发挥细胞保护作用的确切分子机制尚未完全阐明。因此，本研究旨在确定 C 富勒烯是否能预防氧化应激损伤，并探讨 C 富勒烯对糖尿病中细胞凋亡和自噬的影响，以阐明其潜在机制。研究了橄榄油提取的 C 富勒烯对 STZ 糖尿病大鼠海马的影响。在 STZ 糖尿病大鼠的大脑中观察到 Caspase-3、Beclin-1 和氧化应激指标上调，Bcl-2 下调。C 富勒烯暴露 12 周可改善氧化还原失衡，通过调节 Caspase-3、Bcl-2、Beclin-1 和 LC3I/II 含量，改善高血糖诱导的细胞凋亡和自噬流紊乱。此外，C 富勒烯改善了 LC3I/II 比值，防止了自噬流的极度增加。相反，纯净的 C 富勒烯对非糖尿病组的所有研究的凋亡和自噬标志物均无调节作用。因此，油提取的 C 富勒烯在高血糖应激的海马细胞中表现出细胞保护作用。结果证实，纯净的 C 富勒烯纳米颗粒可通过抗氧化、抗凋亡作用和改善自噬流来保护海马细胞免受高血糖应激。此外，C 富勒烯通过 BCL-2/Beclin-1 相互表达调节自噬平衡，可防止海马功能障碍。
