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.
Highlights
Reactive oxygen species (ROS) is a critical factor in enhancing bone resorption and reducing bone formation [1,2]
We suggested that the FSTinduced nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway directly involves the elimination of active oxygen, resulting in antioxidant activity
Our finding showed that FST significantly suppressed DNA damage and apoptosis by reducing reactive oxygen species (ROS) generation in MC3T3-E1 osteoblasts exposed to H2 O2
Summary
Reactive oxygen species (ROS) is a critical factor in enhancing bone resorption and reducing bone formation [1,2]. Excessive levels of ROS cause oxidative damage to various organs and contribute to the pathogenesis and progression of several oxidative stressmediated diseases, including osteoporosis [2,3]. Overproduction of ROS induces oxidative stress, leading to cell death following damage to macromolecules [4,5]. ROS accumulation can contribute to mitochondrial dysfunction, and cytochrome c, which exists between the inner and outer membranes of mitochondria, is released and caspases are activated to induce apoptosis [5,6]. Accumulated results have revealed that excessive production of ROS can lead to bone loss by promoting apoptosis while inhibiting the differentiation of osteoblasts [1,2]. Research on the discovery and mechanism of antioxidants to protect osteoblasts from the accumulation of ROS is being actively conducted
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