The regulatory role of the RANKL/RANK/OPG signaling pathway in the mechanisms of tooth eruption in patients with impacted teeth

Abstract Background Tooth impaction is a common problem in orthodontic practice and in some cases accompanied by pain and pathological changes of surrounding teeth. Understanding the cellular and molecular mechanisms underlying tooth impaction allows finding the most effective orthodontic treatment for patients with impacted teeth (IT). RANK (receptor activator of NF-κB) / RANKL (RANK ligand) / OPG (osteoprotegerin) signaling pathway controls bone resorption and may be involved in the regulation of tooth eruption. The study aimed to evaluate bone remodeling based on the assessment of the RANKL/RANK/OPG status in patients with IT. Methods Bone samples from 18 patients (mean age 25.27 ± 3.34) were divided into 3 groups: 1 – bone tissue of healthy persons (control group); 2 – bone tissue, that was taken near the healthy tooth in patients with tooth impaction; 3 – bone tissue, that was collected near the IT. Levels of RANKL, RANK, OPG, osteocalcin (OC), NF-κB p65 subunit, NFATc1, and caspase-3 were determined by western blotting. The difference between groups was assessed using ANOVA followed by Tukey’s post-hoc test. P-value ≤0.05 was considered statistically significant. Results We established a 1.73-fold elevation of RANK level in the IT area vs. control, indicating the recruitment of preosteoclasts. An increase in RANKL, OPG, and OC content was demonstrated (1.46-, 1.48-, and 1.42-fold respectively), reflecting the high activity of osteoblasts near the IT. Despite the activation of the RANKL/RANK/OPG system in the impaction area, NF-κB and NFATc1 levels did not change compared vs. control, indicating a blocked/delayed process of osteoclastogenesis. We found a decrease in the content of procaspase-3 (1.28-fold), while the level of its active form p17 increased by 2.26 folds near the healthy tooth in patients with IT compared with control. In the area of IT, we observed an increase in procaspase-3 and p17 levels (1.32 and 1.78 folds). This reflects impairments of caspase-3 activation and accumulation of its inactive form in the IT area that may contribute to the tooth eruption failure. Conclusions Tooth impaction may be associated with the disturbances in the caspase-3 cascade activation and the imbalance in the RANKL/RANK/OPG system, and as a result, blocked bone resorption.

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The regulatory role of the RANKL/RANK/OPG signaling pathway in the mechanisms of tooth eruption in patients with impacted teeth

10.21203/rs.2.19720/v5 ◽

2020 ◽

Author(s):

Ludmila Brodetska ◽

Larysa Natrus ◽

Olha Lisakovska ◽

Olexandr Kaniura ◽

Liudmyla Iakovenko ◽

...

Keyword(s):

Bone Resorption ◽

Bone Tissue ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Caspase 3 ◽

Active Form ◽

Tooth Eruption ◽

Control Group ◽

Impacted Teeth ◽

Tooth Impaction

Abstract Background: Tooth impaction is a common problem in orthodontic practice and in some cases accompanied by pain and pathological changes of surrounding teeth. Understanding the cellular and molecular mechanisms underlying tooth impaction allows finding the most effective orthodontic treatment for patients with impacted teeth (IT). RANK (receptor activator of NF-κB) / RANKL (RANK ligand) / OPG (osteoprotegerin) signaling pathway controls bone resorption and may be involved in the regulation of tooth eruption. The study aimed to evaluate bone remodeling based on the assessment of the RANKL/RANK/OPG status in patients with IT. Methods: Bone samples from 18 patients (mean age 25.27±3.34) were divided into 3 groups: 1 – bone tissue of healthy persons (control group); 2 – bone tissue, that was taken near the healthy tooth in patients with tooth impaction; 3 – bone tissue, that was collected near the IT. Levels of RANKL, RANK, OPG, osteocalcin (OC), NF-κB p65 subunit, NFATc1, and caspase-3 were determined by western blotting. The difference between groups was assessed using ANOVA followed by Tukey’s post-hoc test. P-value ≤ 0.05 was considered statistically significant.Results: We established a 1.73-fold elevation of RANK level in the IT area vs. control, indicating the recruitment of preosteoclasts. An increase in RANKL, OPG, and OC content was demonstrated (1.46-, 1.48-, and 1.42-fold respectively), reflecting the high activity of osteoblasts near the IT. Despite the activation of the RANKL/RANK/OPG system in the impaction area, NF-κB and NFATc1 levels did not change compared vs. control, indicating a blocked/delayed process of osteoclastogenesis. We found a decrease in the content of procaspase-3 (1.28-fold), while the level of its active form p17 increased by 2.26 folds near the healthy tooth in patients with IT compared with control. In the area of IT, we observed an increase in procaspase-3 and p17 levels (1.32 and 1.78 folds). This reflects impairments of caspase-3 activation and accumulation of its inactive form in the IT area that may contribute to the tooth eruption failure.Conclusions: Tooth impaction may be associated with the disturbances in the caspase-3 cascade activation and the imbalance in the RANKL/RANK/OPG system, and as a result, blocked bone resorption.

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The regulatory role of the RANKL/RANK/OPG signaling pathway in the mechanisms of tooth eruption in patients with impacted teeth

10.21203/rs.2.19720/v1 ◽

2019 ◽

Author(s):

Petro Flis ◽

Ludmila Brodetska ◽

Olexandr Kaniura ◽

Olha Lisakovska ◽

Larysa Natrus ◽

...

Keyword(s):

Bone Resorption ◽

Bone Tissue ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Caspase 3 ◽

Active Form ◽

Tooth Eruption ◽

Control Group ◽

Impacted Teeth ◽

Tooth Impaction

Abstract Background Tooth impaction is a common problem in orthodontic practice and usually accompanied by pain and pathological changes of surrounding teeth. Understanding the cellular and molecular mechanisms underlying tooth impaction allows finding the most effective way of orthodontic treatment for patients with impacted teeth (IT). The RANK (receptor activator of NF-κB) / RANKL (RANK ligand) / OPG (osteoprotegerin) signaling pathway controls bone resorption and may be involved in the regulation of tooth eruption. The aim of the study was to evaluate the bone remodeling based on the assessment of the RANKL/RANK/OPG status in patients with IT.Methods Bone samples from 20 patients (mean age 15.27, SD = 3.83) were divided into 3 groups: 1 – bone tissue of healthy persons (control group); 2 – bone tissue taken near the healthy tooth in patients with tooth impaction; 3 – bone tissue taken near the IT. Levels of RANKL, RANK, OPG, osteocalcin (OC), NF-κB p65subunit, NFATc1 and caspase-3 were determined by Western blotting. The difference between groups was assessed by one-way ANOVA. P-values less than 0.05 were considered statistically significant.Results We established a 1.73-fold elevation of RANK level in the IT area vs. control, indicating the recruitment of preosteoclasts. An increase in RANKL, OPG and OC content was demonstrated (by 1.46, 1.48, and 1.42 fold respectively), reflecting high activity of osteoblasts near the IT. Despite the activation of the RANKL/RANK/OPG system in the impaction area, NF-κB and NFATc1 levels did not change compared vs. control, indicating a blocked/delayed process of osteoclastogenesis. We found a decrease in the content of procaspase-3 (1.28-fold), while the level of its active form p17 increased by 2.26 fold near the healthy tooth in patients with IT compared with control. In the area of IT we observed an increase in procaspase-3 and p17 levels (1.32 and 1.78 fold). This reflects impairments of caspase-3 activation and accumulation of its inactive form in the IT area that may contribute to the tooth eruption failure.Conclusions Tooth impaction may be associated with the disturbances in the caspase-3 cascade activation and the imbalance in the RANKL/RANK/OPG system, and as a result, blocked bone resorption.

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The regulatory role of the RANKL/RANK/OPG signaling pathway in the mechanisms of tooth eruption in patients with impacted teeth

10.21203/rs.2.19720/v3 ◽

2020 ◽

Author(s):

Ludmila Brodetska ◽

Larysa Natrus ◽

Olha Lisakovska ◽

Olexandr Kaniura ◽

Liudmyla Iakovenko ◽

...

Keyword(s):

Bone Resorption ◽

Bone Tissue ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Caspase 3 ◽

Active Form ◽

Tooth Eruption ◽

Control Group ◽

Impacted Teeth ◽

Tooth Impaction

Abstract Background: Tooth impaction is a common problem in orthodontic practice and in some cases accompanied by pain and pathological changes of surrounding teeth. Understanding the cellular and molecular mechanisms underlying tooth impaction allows finding the most effective orthodontic treatment for patients with impacted teeth (IT). RANK (receptor activator of NF-κB) / RANKL (RANK ligand) / OPG (osteoprotegerin) signaling pathway controls bone resorption and may be involved in the regulation of tooth eruption. The study aimed to evaluate bone remodeling based on the assessment of the RANKL/RANK/OPG status in patients with IT. Methods: Bone samples from 18 patients (mean age 25.27±3.34) were divided into 3 groups: 1 – bone tissue of healthy persons (control group); 2 – bone tissue, that was taken near the healthy tooth in patients with tooth impaction; 3 – bone tissue, that was collected near the IT. Levels of RANKL, RANK, OPG, osteocalcin (OC), NF-κB p65, NFATc1, and caspase-3 were determined by western blotting. The difference between groups was assessed using ANOVA followed by Tukey’s post-hoc test. P-value ≤ 0.05 was considered statistically significant. Results: We established a 1.73-fold elevation of RANK level in the IT area vs. control, indicating the recruitment of preosteoclasts. An increase in RANKL, OPG, and OC content was demonstrated (1.46-, 1.48-, and 1.42-fold respectively), reflecting the high activity of osteoblasts near the IT. Despite the activation of the RANKL/RANK/OPG system in the impaction area, NF-κB and NFATc1 levels did not change compared vs. control, indicating a blocked/delayed process of osteoclastogenesis. We found a decrease in the content of procaspase-3 (1.28-fold), while the level of its active form p17 increased by 2.26 folds near the healthy tooth in patients with IT compared with control. In the area of IT, we observed an increase in procaspase-3 and p17 levels (1.32- and 1.78-fold). This reflects impairments of caspase-3 activation and accumulation of its inactive form in the IT area that may contribute to the tooth eruption failure. Conclusions: Tooth impaction may be associated with the disturbances in the caspase-3 cascade activation and the imbalance in the RANKL/RANK/OPG system, and as a result, blocked bone resorption.

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The regulatory role of the RANKL/RANK/OPG signaling pathway in the mechanisms of tooth eruption in patients with impacted teeth

10.21203/rs.2.19720/v2 ◽

2020 ◽

Author(s):

Ludmila Brodetska ◽

Larysa Natrus ◽

Olha Lisakovska ◽

Olexandr Kaniura ◽

Liudmyla Iakovenko ◽

...

Keyword(s):

Bone Resorption ◽

Bone Tissue ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Caspase 3 ◽

Active Form ◽

Tooth Eruption ◽

Control Group ◽

Impacted Teeth ◽

Tooth Impaction

Abstract Background: Tooth impaction is a common problem in orthodontic practice and in some cases accompanied by pain and pathological changes of surrounding teeth. Understanding the cellular and molecular mechanisms underlying tooth impaction allows finding the most effective orthodontic treatment for patients with impacted teeth (IT). RANK (receptor activator of NF-κB) / RANKL (RANK ligand) / OPG (osteoprotegerin) signaling pathway controls bone resorption and may be involved in the regulation of tooth eruption. The aim of the study was to evaluate the bone remodeling based on the assessment of the RANKL/RANK/OPG status in patients with IT. Methods: Bone samples from 18 patients (mean age 25.27±3.34) were divided into 3 groups: 1 – bone tissue of healthy persons (control group); 2 – bone tissue taken near the healthy tooth in patients with tooth impaction; 3 – bone tissue taken near the IT. Levels of RANKL, RANK, OPG, osteocalcin (OC), NF-κB p65 subunit, NFATc1 and caspase-3 were determined by Western blotting. The difference between groups was assessed by one-way ANOVA. P-values less than 0.05 were considered statistically significant.Results: We established a 1.73-fold elevation of RANK level in the IT area vs. control, indicating the recruitment of preosteoclasts. An increase in RANKL, OPG and OC content was demonstrated (by 1.46, 1.48, and 1.42 fold respectively), reflecting high activity of osteoblasts near the IT. Despite the activation of the RANKL/RANK/OPG system in the impaction area, NF-κB and NFATc1 levels did not change compared vs. control, indicating a blocked/delayed process of osteoclastogenesis. We found a decrease in the content of procaspase-3 (1.28-fold), while the level of its active form p17 increased by 2.26 fold near the healthy tooth in patients with IT compared with control. In the area of IT we observed an increase in procaspase-3 and p17 levels (1.32 and 1.78 fold). This reflects impairments of caspase-3 activation and accumulation of its inactive form in the IT area that may contribute to the tooth eruption failure.Conclusions: Tooth impaction may be associated with the disturbances in the caspase-3 cascade activation and the imbalance in the RANKL/RANK/OPG system, and as a result, blocked bone resorption.

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The regulatory role of the RANKL/RANK/OPG signaling pathway in the mechanisms of tooth eruption in patients with impacted teeth

10.21203/rs.2.19720/v4 ◽

2020 ◽

Author(s):

Ludmila Brodetska ◽

Larysa Natrus ◽

Olha Lisakovska ◽

Olexandr Kaniura ◽

Liudmyla Iakovenko ◽

...

Keyword(s):

Bone Resorption ◽

Bone Tissue ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Caspase 3 ◽

Active Form ◽

Tooth Eruption ◽

Control Group ◽

Impacted Teeth ◽

Tooth Impaction

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Evaluation of MACF1-regulatory non-coding RNA as a potential therapeutic target in Colorectal Cancer

QJM ◽

10.1093/qjmed/hcab088.011 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Rowaida Mohammed Reda M. M Aboushahba ◽

Fayda Ibrahim Abdel Motaleb ◽

Ahmed Abdel Aziz Abou-Zeid ◽

Enas Samir Nabil ◽

Dalia Abdel-Wahab Mohamed ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Wnt Signaling ◽

Cell Line ◽

Signaling Pathway ◽

Therapeutic Target ◽

Molecular Mechanisms ◽

Wnt Signaling Pathway ◽

Control Group ◽

Potential Therapeutic Target

ABSTRACT Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths world-wide. There is an increasing need for the identification of novel biomarkers/targets for early diagnosis and for the development of novel chemopreventive and therapeutic agents for CRC. Recently, MACF1 gene has emerged as a potential therapeutic target in cancer as it involved in processes critical for tumor cell proliferation, invasion and metastasis. It is suggested that MACF1 may function in cancers through Wnt signaling. MiR-34a is a well-known tumor suppressor miRNA.miR-34a targets MACF1 gene as a part of the wnt signaling pathway. In this study, 40 colonic tissues were collected from CRC patients (20) and control subjects (20). miR-34a-5p was assessed by real time PCR in all study groups. The results showed highly significant decrease (P < 0.01) in miR-34a relative expression in the CRC group (median RQ 0.13) when compared to the benign group (median RQ 5.3) and the healthy control group (median RQ 19.63). miR-34a mimic and inhibitor were transfected in CaCo-2 cell line and proliferation was assessed. The transfection of the cell line with miR-34a mimic decreased cell proliferation. Our study suggests that miR-34a-5p targets MACF1 gene as a part of the wnt signaling pathway leading to the involvement in the molecular mechanisms of CRC development and progression.

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Nox4 Mediates RANKL-induced ER-Phagy and Osteoclastogenesis via Activating ROS/PERK/eIF-2α/ATF4 Pathway

10.21203/rs.3.rs-34288/v1 ◽

2020 ◽

Author(s):

Jing Sun ◽

wugui chen ◽

Songtao Li ◽

Sizhen Yang ◽

Ying Zhang ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Bone Resorption ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Nuclear Factor Κb ◽

Protein Levels ◽

Unfolded Protein ◽

Regulatory Effects ◽

Protein Response

Abstract Background: Receptor activator of nuclear factor-κB ligand (RANKL) has been found to induce osteoclastogenesis and bone resorption. However, the underlying molecular mechanisms remain unclear. Methods: Osteoclastogenesis was evaluated by number of TRAP-positive multinuclear (≥3) osteoclasts, bone resorption pits and expression levels of related genes. Autophagy activity were evaluated by LC3-II/LC3-I ratio, number of autophagic vacuoles and adenovirus-mRFP-GFP-tagged LC3 reporting system; Inhibitor chloroquine (CQ) was used to verified the role of autophagy in RANKL-induced osteoclastogenesis; Via downregulating Nox4 with inhibitor (DPI) and retrovirus-conveyed shRNA, we further explored the importance of Nox4 in RANKL-induced autophagy and osteoclastogenesis, as well as the regulatory effects of Nox4 on nonmitochondrial reactive oxygen species (ROS) and PERK/eIF-2α/ATF4 pathway. Intracellular ROS scavenger (NAC), mitochondrial-targeted antioxidant (MitoTEMPO) and inhibitor of PERK (GSK2606414) were also employed to investigate the role of ROS and PERK/eIF-2α/ATF4 pathway in RANKL-induced autophagy and osteoclastogenesis. Results: RANKL markedly increased autophagy, while CQ treatment caused reduction of RANKL-induced autophagy and osteoclastogenesis. Consistent with the increased autophagy, the protein levels of Nox4 were significantly increased, and Nox4 was selectively localized within the endoplasmic reticulum (ER) after RANKL stimulation. DPI and shRNA efficiently decreased the protein level and (or) activity of Nox4 in the ER and inhibited RANKL-induced autophagy and osteoclastogenesis. Mechanistically, we found that Nox4 regulates RANKL-induced autophagy activation and osteoclastogenesis by stimulating the production of nonmitochondrial ROS. Additionally, Nox4-derived nonmitochondrial ROS dramatically activate PERK/eIF-2α/ATF4, which is a critical unfolded protein response (UPR)-related signaling pathway during ER stress. Blocking the activation of the PERK/eIF-2α/ATF4 signaling pathway either by Nox4 shRNA, ROS antioxidant or PERK inhibitor (GSK2606414) treatment significantly inhibited endoplasmic reticulum autophagy (ER-phagy) during RANKL-induced osteoclastogenesis. Conclusions: Our findings provide new insights into the processes of RANKL-induced osteoclastogenesis and will help the development of new therapeutic strategies for osteoclastogenesis-related diseases.

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Beneficial Impact and Molecular Mechanism of Bacillus Coagulans on Piglets Intestine

10.20944/preprints201805.0084.v1 ◽

2018 ◽

Author(s):

Tao Wu ◽

Yang Lv ◽

Xueni Li ◽

Lin Zhang ◽

Yutao Shi ◽

...

Keyword(s):

Molecular Mechanism ◽

Molecular Mechanisms ◽

Caspase 3 ◽

Bacillus Coagulans ◽

Basal Diet ◽

Control Group ◽

Villus Height ◽

Intestinal Integrity ◽

Beneficial Impact ◽

Related Proteins

This research was to investigate beneficial impact and molecular mechanism of B. coagulans on piglets intestine. Twenty-four 21 days old weaned piglets were allotted to three treatments: control group (basal diet), B6 group (basal diet + 2×106 CFU/g B. coagulans), B7 group (basal diet + 2×107 CFU/g B. coagulans). The results showed that compared with control group, B6 and B7 group significantly decreased diarrhea rate and the concent of CHOL, GGT and DAO in plasma; decreased villus height and increase crypt depth in jejunum and ileum; increased the activities of SOD and CAT and decreased the concent of MDA and H2O2 in intestine. These data suggested that supplementing B. coagulans had beneficial impacts on promoting nutrients metabolism, maintaining intestinal integrity and alleviating oxidative stress and diarrhea. Futher research of molecular mechanisms showed that, these beneficial impacts were regulated by changing expression levels of related proteins (including HSP70, Caspase-3, Bax, Villin and Occludin), and genes (including RPL4, IFN-α, IFN-β, IFN-γ, MX1, MX2, OAS1, IL-1β, IL-4, CXCL-9, CCL-2, AQP3, SGLT-1, LPL, INSR and b0,+AT), and altering community composition of gut microbiota (particularly family Clostridiaceae, Enterobacteriaceae, and Veillonellaceae and genus Prevotella, Turicibacter, and Lactobacillus).

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Effect of SRY-Related High Mobility Group Box 9 on Extracellular Signal-Regulated Kinase/p38 Signaling Pathway in Glioma

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2531 ◽

2021 ◽

Vol 11 (1) ◽

pp. 171-175

Author(s):

Tianlong Quan ◽

Chunhua Zhang ◽

Xin Song ◽

Lu Wang

Keyword(s):

Cell Proliferation ◽

Signaling Pathway ◽

Cell Invasion ◽

Cell Apoptosis ◽

Caspase 3 ◽

High Mobility ◽

Negative Control ◽

Glioma Cell Line ◽

High Mobility Group ◽

Control Group

As a common malignant tumor in neurosurgery, glioma is characterized as high incidence rate, easy to invade, metastasize and recurrent. It is difficult to treat and has a poor prognosis. The gliomas pathogenesis is complex and has not been fully resolved. Therefore, finding effective molecular targets for glioma is beneficial to improve therapeutic effect. The SRY-related high mobility group box 9 (SOX9) gene involves in mammalian development and is significantly increased in glioma. However, SOX9’s role in gliomas is unclear. The glioma cell line U87 was assigned into control group, scramble group that was transfected with siRNA negative control, and SOX9 siRNA group that was transfected with SOX9 siRNA followed by analysis of SOX9 mRNA and protein level by qPCR and Western blot, cell proliferation by MTT assay, cell apoptosis by Caspase 3 activity assay, cell invasion by Transwell assay, and MMP-9 level by ELISA. SOX9 siRNA transfection significantly downregulated SOX9 mRNA and protein expressions, inhibited U87 cell proliferation, enhanced Caspase 3 activity, suppressed cell invasion of U87, decreased the secretion of MMP-9 in the supernatant, and reduced ERK1/2 and P38 phosphorylation levels (P < 0.05). SOX9 can regulate the progression of glioma by regulating ERK/P38 signaling pathway, promoting cell apoptosis, inhibiting cell proliferation, and restraining cell invasion.

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Effects of Hydrogen-rich Water on the PI3K/AKT Signaling Pathway in Rats with Myocardial Ischemia-reperfusion Injury

Current Molecular Medicine ◽

10.2174/1566524019666191105150709 ◽

2020 ◽

Vol 20 (5) ◽

pp. 396-406 ◽

Cited By ~ 3

Author(s):

Liangtong Li ◽

Xiangzi Li ◽

Zhe Zhang ◽

Li Liu ◽

Tongtong Liu ◽

...

Keyword(s):

Reperfusion Injury ◽

Signaling Pathway ◽

Caspase 3 ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Akt Signaling ◽

Control Group ◽

Akt Signaling Pathway ◽

Expression Levels ◽

Water Group

Background: The effects of hydrogen-rich water on PI3K/AKT-mediated apoptosis were studied in rats subjected to myocardial ischemia-reperfusion injury (MIRI). Methdos: Sixty rats were divided randomly into a hydrogen-rich water group and a control group. The hearts were removed and fixed in a Langendorff device. Hearts from the control group were perfused with K-R solution, and hearts from the hydrogen-rich water group was perfused with K-R solution + hydrogen-rich water. The two treatment groups were then divided randomly into pre-ischemic period, ischemic period and reperfusion period groups(10 rats per group), which were subjected to reverse perfusion for 10 min, normal treatment for 20 min, and reperfusion for 20 min, respectively. The mRNA and protein expression levels of PI3K, AKT, p-AKT, FoxO1, Bim and Caspase-3 in each group were detected by RT-qPCR, immunohistochemistry (IHC) and Western blotting. Caspase-3 activity was detected by spectrophotometry. Results: Among the hydrogen-rich water group, the PI3K/AKT signaling pathway was significantly activated, and FoxO1, Bim, and Caspase-3 mRNA and protein levels were significantly decreased in ischemia-reperfusion subgroup compared with the preischemic and ischemic subgroups. In the ischemia-reperfusion hydrogen-rich water group, PI3K, AKT and p-AKT mRNA and protein expression levels were increased while the FoxO1, Bim and Caspase-3 expression levels were significantly decreased compared with those in the corresponding control group (p<0.05). Conclusion: Hydrogen-rich water can activate the PI3K/AKT signaling pathway, alleviate ischemia-reperfusion injury in isolated rat hearts, and inhibit cardiomyocyte apoptosis.

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