WITHDRAWN: β4 ameliorates oxidative damage and apoptosis through ERK/MAPK and 5-HT1A signaling pathway in Aβ insulted SH-SY5Y cells

Abstract

Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder seriously endangering the physical and mental health of the elderly, while no effective treatments and drugs in clinical practice are available. Thymosin β4 (Tβ4) is a multifunctional polypeptide involved in many physiological and pathological processes including AD. This study aims to understand the function and molecular mechanism of Tβ4 in the development of AD. Neuroblastoma cell line SH-SY5Y was treated with β-amyloid (Aβ) to induce AD-like pathological changes, which serves as Alzheimer's disease model. Tβ4 was overexpressed in SH-SY5Y cells by lentivirus infection, and downregulated by siRNA transfection. Apoptosis of transfected SH-SY5Y cells after Aβ-treatment was examined by western blot and flow cytometry. Apoptotic proteins and Tβ4-related signaling pathways were also investigated by western blot. We found that Tβ4 overexpression increased viability and suppressed apoptosis of Aβ-treated SH-SY5Y cells. Tβ4 ameliorated oxidative damage and suppressed reactive oxygen species production in Aβ-treated SH-SY5Y cells. Consistently, Tβ4 overexpression down-regulated the expression levels of pro-apoptotic markers such as Caspase-3, Caspase-8, and Bax, while up-regulated the expression level of anti-apoptotic gene Bcl-2 in Aβ-stimulated SH-SY5Y cells. Mechanistically, we demonstrated that Tβ4 dampened ERK/p38 MAPK signaling and enhanced 5-HTR1A expression in Aβ-treated SH-SY5Y cells. Moreover, we revealed that Tβ4 inhibited the activation of ERK pathway through up-regulating 5-HTR1A in Aβ-treated SH-SY5Y cells. Taken together, our findings provide evidences to support the neuroprotective role of Tβ4 and might open up new therapeutic applications of Tβ4 in AD treatment.