Protection against Oxidative Stress-Induced Apoptosis by Fermented Sea Tangle (Laminaria japonica Aresch) in Osteoblastic MC3T3-E1 Cells through Activation of Nrf2 Signaling Pathway

Abstract

The purpose of the present study was to explore the efficacy of fermented extract of sea tangle (Laminaria japonica Aresch, FST) with Lactobacillus brevis on DNA damage and apoptosis in hydrogen peroxide (H2O2)-stimulated osteoblastic MC3T3-E1 cells and clarify related signaling pathways. Our results showed that exposure to FST significantly improved cell viability, inhibited apoptosis, and suppressed the generation of reactive oxygen species (ROS) in H2O2-stimulated cells. In addition, H2O2 triggered DNA damage in MC3T3-E1 cells was markedly attenuated by FST pretreatment. Moreover, H2O2-induced mitochondrial dysfunctions associated with apoptotic events, including loss of mitochondrial membrane potential (MMP), decreased Bcl-2/Bcl-2 associated x-protein (Bax) ratio, and cytosolic release of cytochrome c, were reduced in the presence of FST. FST also diminished H2O2-induced activation of caspase-3, which was associated with the ability of FST to protect the degradation of poly (ADP-ribose) polymerase. Furthermore, FST notably enhanced nuclear translocation and phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2) in the presence of H2O2 with concomitant upregulation of heme oxygenase-1 (HO-1) expression. However, artificial blockade of this pathway by the HO-1 inhibitor, zinc protoporphyrin IX, greatly abolished the protective effect of FST against H2O2-induced MC3T3-E1 cell injury. Taken together, these results demonstrate that FST could protect MC3T3-E1 cells from H2O2-induced damage by maintaining mitochondrial function while eliminating ROS along with activation of the Nrf2/HO-1 antioxidant pathway.

Oxidative Stress and Inflammation in Osteoporosis: Molecular Mechanisms Involved and the Relationship with microRNAs

“…GC-induced apoptosis due to oxidative stress is mediated by ERK1/2 activation in MC3T3-E1 cells [ 85 ] and involves the downregulation of Nrf2 in BMSCs [ 86 ]. It is possible that, in osteoblasts, there is a correlation between the reduced activation of Nrf2 due to oxidative stress [ 49 ] and ROS-induced apoptosis, considering that the activation of the γNrf2 signaling cascade inhibits oxidative injury and apoptosis in these cells [ 87 , 88 ].…”

Advances in the study of traditional Chinese medicine affecting bone metabolism through modulation of oxidative stress

“…Data shows that in the presence of H 2 O 2 , the important metabolites Fermented Sea T angle (FST) of the traditional Chinese medicine Saccharina japonica [Phaeophyceae] significantly promotes nuclear translocation and phosphorylation of Nrf2, accompanied by upregulation of HO-1 expression. Kim et al (Kim et al, 2021) further confirmed that FST inhibits oxidative stress through the Nrf2/HO-1 pathway by pretreating MC3T3-E1 cells with the HO-1 inhibitor zinc protoporphyrin (ZnPP) to block the Nrf2/HO-1 signaling pathway. Studies have shown that pre-treatment with ZnPP significantly abolishes the protective effect of FST on H 2 O 2induced damage in MC3T3-E1 cells.…”

Protective Effect of Fermented Sea Tangle Extract on Skin Cell Damage Caused by Particulate Matter

“…Moreover, most glutamic acid in L. japonica is converted to gamma-aminobutyric acid (GABA) [18]. GABA-enriched FST extract not only has antioxidant effects but also prevents or treats diseases, such as cognitive disorders and liver damage [19][20][21][22]. GABA improves skin moisture, skin wrinkles, and epidermal thickness on human skin cells and hairless mice [23].…”