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Sodium tanshinone IIA silate inhibits oxygen-glucose deprivation/recovery-induced cardiomyocyte apoptosis via suppression of the NF-?B/TNF-? pathway.

ABSTRACT: BACKGROUND AND PURPOSE: Inhibition of apoptosis may attenuate the irreversible injury associated with reperfusion. In the current study, we focused on the cytoprotective effects and the underlying mechanism of sodium tanshinone IIA silate (STS) against damage induced by oxygen-glucose deprivation/recovery (OGD/R). in H9c2 cardiomyocytes and the underlying mechanisms. EXPERIMENTAL APPROACH: We used a model of cardiac ischaemia/reperfusion, OGD/R in H9c2 cardiomyocytes, to assess the cardioprotective effects of STS. Apoptosis of cells was measured with Hoechst 33342-based fluorescence microscopy, and annexin V-FITC-based flow cytometry. Caspase-3 and caspase-8 activities and mitochondrial membrane potential were also measured using commercial kits. TNF-? in the cell culture supernatant fractions were measured with sandwich elisa, and protein levels assayed using Western blot. KEY RESULTS: STS inhibited OGD/R-induced apoptosis by suppressing JNK-mediated activation of NF-?B, TNF-? expression, activation of caspase-3 and caspase-8 and the Bax/Bcl-2 ratio. Additionally, positive feedback between NF-?B and TNF-? and amplification of TNF-? were inhibited, suggesting that STS plays a protective role against apoptosis in cardiomyocytes, even upon activation of pro-inflammatory cytokines. Interestingly, the cytoprotective effects of STS on OGD/R-induced apoptosis and promotion of cell survival were attenuated after inhibition of PI3K. CONCLUSION AND IMPLICATIONS: The inhibitory effects of STS on TNF-? and positive feedback signalling of the NF-?B/TNF-? pathways may play important roles in myocardial protection against ischaemia/reperfusion. These protective effects of STS are mediated by suppressing JNK activity through activation of the PI3K-Akt pathway.

SUBMITTER: Wu WY

PROVIDER: S-EPMC3696329 | biostudies-other | 2013 Jul

REPOSITORIES: biostudies-other

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Sodium tanshinone IIA silate inhibits oxygen-glucose deprivation/recovery-induced cardiomyocyte apoptosis via suppression of the NF-κB/TNF-α pathway.

Wu Wen-Yu WY Wang Wen-Yi WY Ma Yan-Ling YL Yan Hong H Wang Xin-Bo XB Qin Yin-Lin YL Su Mei M Chen Tao T Wang Yi-Ping YP

British journal of pharmacology 20130701 5

<h4>Background and purpose</h4>Inhibition of apoptosis may attenuate the irreversible injury associated with reperfusion. In the current study, we focused on the cytoprotective effects and the underlying mechanism of sodium tanshinone IIA silate (STS) against damage induced by oxygen-glucose deprivation/recovery (OGD/R). in H9c2 cardiomyocytes and the underlying mechanisms.<h4>Experimental approach</h4>We used a model of cardiac ischaemia/reperfusion, OGD/R in H9c2 cardiomyocytes, to assess the ...[more]

PMID: 23517194

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Project description:Hypoxic ischemic encephalopathy (HIE) is the most common brain injury following hypoxia and/or ischemia caused by various factors during the perinatal period, resulting in detrimental neurological deficits in the nervous system. Tanshinone IIA (Tan‑IIA) is a potential agent for the treatment of cardiovascular and cerebrovascular diseases. In this study, the efficacy of Tan‑IIA was investigated in a newborn mouse model of HIE. The dynamic mechanism of Tan‑IIA was also investigated in the central nervous system of neonate mice. Intravenous injection of Tan‑IIA (5 mg/kg) was administered and changes in oxidative stress, inflammation and apoptosis‑associated proteins in neurons. Histology and immunohistochemistry was used to determine infarct volume and the number of damaged neurons by Fluoro‑Jade C staining. The effects of Tan‑IIA on mice with HIE were evaluated by body weight, brain water content, neurobehavioral tests and blood‑brain barrier permeability. The results demonstrated that the apoptosis rate was decreased following Tan‑IIA administration. Expression levels of pro‑apoptotic proteins, caspase‑3 and caspase‑9 and P53 were downregulated. Expression of Bcl‑2 anti‑apoptotic proteins was upregulated by Tan‑IIA treatment in neuro. Results also found that Tan‑IIA treatment decreased production of inflammatory cytokines such as interleukin‑1, tumor necrosis factor‑α, C‑X‑C motif chemokine 10, and chemokine (C‑C motif) ligand 12. Oxidative stress was also reduced by Tan‑IIA in neurons, as determined by the expression levels of superoxide dismutase, glutathione and catalase, and the production of reactive oxygen species. The results demonstrated that Tan‑IIA treatment reduced the infarct volume and the number of damaged neurons. Furthermore, body weight, brain water content and blood‑brain barrier permeability were markedly improved by Tan‑IIA treatment of newborn mice following HIE. Furthermore, the results indicated that Tan‑IIA decreased Toll‑like receptor‑4 (TLR‑4) and nuclear factor‑κB (NF‑κB) expression in neurons. TLR‑4 treatment of neuronal cell in vitro addition stimulated NF‑κB activity, and further enhanced the production of inflammatory cytokines and oxidative stress levels in neurons. In conclusion, these results suggest that Tan‑IIA treatment is beneficial for improvement of HIE through TLR‑4‑mediated NF‑κB signaling.

Dataset Information

Sodium tanshinone IIA silate inhibits oxygen-glucose deprivation/recovery-induced cardiomyocyte apoptosis via suppression of the NF-?B/TNF-? pathway.

Publications

Sodium tanshinone IIA silate inhibits oxygen-glucose deprivation/recovery-induced cardiomyocyte apoptosis via suppression of the NF-κB/TNF-α pathway.

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