Isorhamnetin, 6-OHDA kaynaklı SH-SY5Y hücrelerinde AKT / mTOR'u aktive etmek için FOSL1'i hedefleyerek dopaminerjik nöronal hasarı iyileştirir.

Araştırma özeti

Aşağıdaki metin kaynak makalenin lisansı doğrulanmış orijinal özetidir. cc by

Parkinson's disease (PD) is a chronic neurodegenerative disorder caused by loss of dopaminergic neurons in the substantia nigra compacta, which may result from mitochondrial dysfunction and oxidative stress. Isorhamnetin (Iso) has important antioxidative stress and antiapoptotic effects, this study investigated the effects of Iso on PD in vitro and its underlying mechanisms using a model of 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y cell damage. The results showed that Iso significantly ameliorated 6-OHDA-induced SH-SY5Y cell injury, including decreased cell viability, increased apoptosis and senescence, and oxidative stress injury. Senescence-associated β-galactosidase (SA-β) staining, Western blot (WB), and immunofluorescence suggested that Iso significantly decreased the number of SA-β+ cells and the levels of senescence-associated proteins p21 and p16, and enhanced tyrosine hydroxylase level. Iso markedly reduced the number of apoptotic cells and the levels of cleaved caspase-3 and BAX, as detected by CCK-8, flow cytometry, and WB. The results of DCFH-DA, JC-1 staining, and the measurement of malondialdehyde (MDA) and superoxide dismutase (SOD) content indicated that Iso elevated reactive oxygen species (ROS) generation and mitochondrial membrane potential, lowered MDA content and raised SOD level in the 6-OHDA group. In-depth investigation revealed that Iso activated the AKT/mTOR signal via reducing the expression level of Fos-like antigen (FOSL1), which further exerted the protective effect in SH-SY5Y cells. Overexpression of FOSL1 attenuated the effect of Iso by inhibiting the AKT/mTOR signaling pathway. Taken together, Iso protects against senescence, apoptotic, and oxidative stress injury by targeting FOSL1 to activate the AKT/mTOR signaling pathway in 6-OHDA-induced SH-SY5Y cells, which may provide new insights for PD treatment.NEW & NOTEWORTHY Isorhamnetin (Iso) ameliorated neuronal activity damage, senescence, apoptosis, and oxidative stress injury in 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y cells. Iso activated AKT/mTOR signaling pathway via inhibiting Fos-like antigen (FOSL1) in 6-OHDA-induced SH-SY5Y cells. Overexpression of FOSL1 attenuated the protective effect of Iso against 6-OHDA-induced neuronal damage in SH-SY5Y cells.

İlgili konular