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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.
Br J Pharmacol. 2013 Jul; 169(5):1058-71.BJ

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-α 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-κB, TNF-α expression, activation of caspase-3 and caspase-8 and the Bax/Bcl-2 ratio. Additionally, positive feedback between NF-κB and TNF-α and amplification of TNF-α 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-α and positive feedback signalling of the NF-κB/TNF-α 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.

Authors+Show Affiliations

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

23517194

Citation

Wu, Wen-Yu, et al. "Sodium Tanshinone IIA Silate Inhibits Oxygen-glucose Deprivation/recovery-induced Cardiomyocyte Apoptosis Via Suppression of the NF-κB/TNF-α Pathway." British Journal of Pharmacology, vol. 169, no. 5, 2013, pp. 1058-71.
Wu WY, Wang WY, Ma YL, et al. Sodium tanshinone IIA silate inhibits oxygen-glucose deprivation/recovery-induced cardiomyocyte apoptosis via suppression of the NF-κB/TNF-α pathway. Br J Pharmacol. 2013;169(5):1058-71.
Wu, W. Y., Wang, W. Y., Ma, Y. L., Yan, H., Wang, X. B., Qin, Y. L., Su, M., Chen, T., & Wang, Y. P. (2013). Sodium tanshinone IIA silate inhibits oxygen-glucose deprivation/recovery-induced cardiomyocyte apoptosis via suppression of the NF-κB/TNF-α pathway. British Journal of Pharmacology, 169(5), 1058-71. https://doi.org/10.1111/bph.12185
Wu WY, et al. Sodium Tanshinone IIA Silate Inhibits Oxygen-glucose Deprivation/recovery-induced Cardiomyocyte Apoptosis Via Suppression of the NF-κB/TNF-α Pathway. Br J Pharmacol. 2013;169(5):1058-71. PubMed PMID: 23517194.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sodium tanshinone IIA silate inhibits oxygen-glucose deprivation/recovery-induced cardiomyocyte apoptosis via suppression of the NF-κB/TNF-α pathway. AU - Wu,Wen-Yu, AU - Wang,Wen-Yi, AU - Ma,Yan-Ling, AU - Yan,Hong, AU - Wang,Xin-Bo, AU - Qin,Yin-Lin, AU - Su,Mei, AU - Chen,Tao, AU - Wang,Yi-Ping, PY - 2012/10/20/received PY - 2013/02/20/revised PY - 2013/03/12/accepted PY - 2013/3/23/entrez PY - 2013/3/23/pubmed PY - 2015/3/31/medline SP - 1058 EP - 71 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 169 IS - 5 N2 - 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-α 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-κB, TNF-α expression, activation of caspase-3 and caspase-8 and the Bax/Bcl-2 ratio. Additionally, positive feedback between NF-κB and TNF-α and amplification of TNF-α 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-α and positive feedback signalling of the NF-κB/TNF-α 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. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/23517194/Sodium_tanshinone_IIA_silate_inhibits_oxygen_glucose_deprivation/recovery_induced_cardiomyocyte_apoptosis_via_suppression_of_the_NF_κB/TNF_α_pathway_ L2 - https://doi.org/10.1111/bph.12185 DB - PRIME DP - Unbound Medicine ER -