Effect of high-frequency low-intensity pulsed electric field on protecting SH-SY5Y cells against hydrogen peroxide and β-amyloid-induced cell injury via ERK pathway

Abstract

As the most common type of neurodegenerative diseases (NDDs), Alzheimer’s disease (AD) is thought to be caused mainly by the excessive aggregation of β-amyloid protein (Aβ). However, a growing number of studies have found that reactive oxygen species (ROS) play a key role in the onset and progression of AD. The present study aimed to probe the neuroprotective effect of high-frequency low-intensity pulsed electric field (H-LIPEF) for SH-SY5Y cells against hydrogen peroxide (H2O2) and Aβ-induced cytotoxicity. By looking in a systematic way into the frequency- and amplitude-dependent neuroprotective effect of pulsed electric field (PEF), the study finds that H-LIPEF at 200 Hz produces the optimal protective effect for SH-SY5Y cells. The underlying mechanisms were confirmed to be due to the activation of extracellular signal-regulated kinase (ERK) pathway and the downstream prosurvival and antioxidant proteins. Because the electric field can be modified to focus on specific area in a non-contact manner, the study suggests that H-LIPEF holds great potential for treating NDDs, whose effect can be further augmented with the administering of drugs or natural compounds at the same time.

Protection of high-frequency low-intensity pulsed electric fields and BDNF for SH-SY5Y cells against hydrogen peroxide-induced cell damage

“…As shown in Fig 2B, we found a slight protective effect of these concentrations of BDNF against H 2 O 2 -induced cell oxidation. On the other hand, in the combination treatment, SH-SY5Y cells were pretreated with H-LIPEF and BDNF for 4 h, and then exposed to 500 μM H 2 O 2 in the continuous administration of H-LIPEF for another 24 h. In present work, we applied the most effective H-LIPEF parameters (200 Hz, 10 V/cm, and 2 ms pulse duration) previously used by our team for neuroprotection study [34] to human neural cells SH-SY5Y. As shown in Fig 2C, the cell viability decreased to about half of the control group after treating SH-SY5Y cells with 500 μM H 2 O 2 for 24 h. When cells were treated by combination treatment with H-LIPEF and BDNF, the cell viability was significantly rescued.…”

“…Furthermore, it is known that both phosphorylated CREB and Nrf2 proteins can regulate the expression of Bcl-2 family proteins [39, 40], and the Bcl-2/Bax ratio determines whether the neurons undergo survival or death after being stimulated [33, 34, 41]. Therefore, the expressions of Bcl-2 and Bax proteins were also measured in this study.…”

“…The applied electric signal was characterized by a pulse train waveform (Fig 1B) with various field strengths and frequencies for different applications. In this study, we used the electric field strength of 10 V/cm at 200 Hz, which was adopted in our previous study to be the optimal H-LIPEF condition for neuroprotection on SH-SY5Y cell line [34].…”

“…As a transcription factor that regulates the expression of pro-survival proteins, CREB plays an important role in neuronal survival [37]. Furthermore, it is known that both phosphorylated CREB and Nrf2 proteins can regulate the expression of Bcl-2 family proteins [39,40], and the Bcl-2/Bax ratio determines whether the neurons undergo survival or death after being stimulated [33,34,41]. Therefore, the expressions of Bcl-…”

“…Because oxidative stress plays a key role in the etiology of neurodegenerative diseases, reducing oxidative stress is often a top priority for neuroprotection. As for neuroprotection study [34] to human neural cells SH-SY5Y. As shown in Fig.…”