Sesamin protects SH-SY5Y cells against mechanical stretch injury and promoting cell survival

Abstract

BackgroundSesamin is a well-known antioxidant extracted from sesame seeds that exhibits various curative effects. The present study investigated whether sesamin would protect neuroblastoma SH-SY5Y cells against mechanical stretch injury-induced increases in reactive oxygen species (ROS) and apoptosis. Additionally, the mechanisms underlying these actives were investigated. Following exposure to mechanical stretch injury, cells were incubated for further investigations. Lactate dehydrogenase and Cell Counting Kit-8 assays were used to assess cell viability, and a terminal deoxynucleotidyl transferase dUTP nick end labeling assay and flow cytometric analysis were performed to evaluate changes in mitochondrial membrane potential (ΔΨm). Furthermore, intracellular levels of ROS production were measured by 20, 70-dichlorofluorescein diacetate staining, the mRNA levels of matrix metallopeptidase 9 (MMP-9) were evaluated using real-time polymerase chain reaction analysis, and the determinations had also been made on related proteins by Western blot analysis.ResultsExposure to mechanical stretch injury significantly decreased cell viability but this decrease was attenuated by pretreatment with sesamin (50 μM). Sesamin also significantly inhibited mechanical stretch injury-induced increases in intracellular ROS production, attenuated declines in ΔΨm, diminished the expressions of pro-apoptotic proteins, and decreased cell apoptosis. Stretch injury increased Bax and cleaved caspase 3 levels, enhanced the gene expression of MMP-9, increased the phosphorylation levels of Akt, p38, and JNK and decreased Bcl-2 levels in the cells. However, pretreatment with sesamin reduced the mechanical stretch injury-induced overexpression of MMP-9.ConclusionsSesamin protected SH-SY5Y cells against stretch injury by attenuating increases in ROS levels and suppressing apoptosis. Accordingly, sesamin seems to be a potentially therapeutic agent in the treatment of traumatic brain injury.Electronic supplementary materialThe online version of this article (doi:10.1186/s12868-017-0378-8) contains supplementary material, which is available to authorized users.

Effects of Sesamin, the Major Furofuran Lignan of Sesame Oil, on the Amplitude and Gating of Voltage-Gated Na+ and K+ Currents

“…It should be noticed that the neurological or cardioprotective actions caused by SSM, SesA, or other structurally similar compounds, as described previously [42,[46][47][48][49][50][51][52][53], can be intimately linked to their direct actions on the amplitude and gating of ion currents (e.g., I Na ). Similar to the ranolazine or perampanel action on I Na described previously [23,25], the inhibitory effect of SSM on ion currents seen herein may be responsible for its wide spectrum of effects observed in vivo [3,54].…”

“…For example, as the modeled cell was exposed to 1 µM SSM, the occupancy probability in the O state mildly decreased from 0.57 to 0.52, while that in the OB state resulted in a reduction from 0.079 to 0.046. to 1 μM SSM, the occupancy probability in the O state mildly decreased from 0.57 to 0.52, while that in the OB state resulted in a reduction from 0.079 to 0.046. The state diagram of a Markovian model for the NaV channel (i.e., SCN8A channel) depicted in (A) was adopted from a recent study [42]. The solutions to the ordinary differential equations in the current study were implemented in the XPP software package, and the default values for detailed numerical parameters are identical to those demonstrated previously [42], except that the values of ε (i.e., voltage-independent transition rate from the open to blocked state) and maximal conductance of INa in the control (i.e., SSM was not present) were arbitrarily assigned to be 0.3 msec −1 and 3.6 nS, respectively.…”

“… Numerical simulations of the SSM-mediated inhibition of voltage-gated Na + currents ( I Na ). The state diagram of a Markovian model for the Na V channel (i.e., SCN8A channel) depicted in ( A ) was adopted from a recent study [ 42 ]. The solutions to the ordinary differential equations in the current study were implemented in the XPP software package, and the default values for detailed numerical parameters are identical to those demonstrated previously [ 42 ], except that the values of ε (i.e., voltage-independent transition rate from the open to blocked state) and maximal conductance of I Na in the control (i.e., SSM was not present) were arbitrarily assigned to be 0.3 msec −1 and 3.6 nS, respectively.…”

Stretching magnitude–dependent inactivation of AKT by ROS led to enhanced p53 mitochondrial translocation and myoblast apoptosis

“…Our previous study subjected C2C12 myoblasts to different stretches (magnitudes of 5, 10, 15, and 20%), and demonstrated that 15 and 20% stretches reduced cell viability because of elevated apoptosis, whereas 5 and 10% stretches did not (Tan et al ., 2009). The present study further confirmed the contribution of ROS overproduction to HMS-induced C1C12 myoblast apoptosis by using ROS scavenger NAC, consistent with some other murine cell types such as SH-SY5Y cell and ATII cell that were rescued from stretch-induced apoptosis by inhibition of ROS (Kuhn et al ., 2017; Xu et al ., 2017).…”

Neuroprotective Effects of Serpina3k in Traumatic Brain Injury

“…The cells were seeded into BioFlex® Six-well Culture Plates (Flexcell International, Burlington, NC, USA) with collagen-coated silastic membranes at a density of 0.5 × 10 5 /cm 2 . Cells were subjected to biaxial SI with the Cell Injury Controller II instrument (Virginia Commonwealth University, Richmond, VA, USA), which released a 50-ms burst of nitrogen gas that caused a 7.5-mm downward deformation of the silastic membrane and adherent cells; this is analogous to the mechanical stress experienced by brain tissue during rotational acceleration and deceleration injury (3, 21).…”