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DIDS attenuates staurosporine-induced cardiomyocyte apoptosis by PI3K/Akt signaling pathway: activation of eNOS/NO and inhibition of Bax translocation.
Cell Physiol Biochem. 2008; 22(1-4):177-86.CP

Abstract

AIMS

4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), a non-selective chloride channel blocker, has been shown to prevent cell apoptosis, however, the underlying mechanisms remain undefined, thus the present study was to explore whether phosphatidylinositol 3'-kinase (PI3K)/Akt and its downstream molecules are involved in the cytoprotective effect of DIDS.

METHODS

Neonatal rat cardiomyocytes were exposed to staurosporine (STS) in the presence or absence of DIDS. Cell viability, apoptosis and expressions of Akt, phospho-Akt (p-Akt), eNOS, phospho-eNOS (p-eNOS), Bcl-2/Bax and nitric oxide (NO) production were determined, and Bax translocation was assessed by double immunofluorescence labeling and Western blotting.

RESULTS

DIDS markedly improved cell viability and exerted an anti-apoptotic effect on STS-exposed cardiomyocytes. DIDS resulted in a 2.1-fold increase of p-Akt over control levels, prevented the reduction in eNOS expression and phospho-eNOS levels induced by STS and significantly increased NO production (all P<0.01 vs. STS alone). Treatment with LY294002, a selective PI3K inhibitor, abolished DIDS-induced increases in p-Akt, eNOS, p-eNOS and NO production, and completely abrogated the DIDS-induced anti-apoptotic effect (P<0.01). Treatment with L-NAME, a non-selective NOS inhibitor similarly inhibited the increased NO but only partly abolished protective effects of DIDS (P<0.05). In addition, DIDS effectively inhibited STS-induced Bax translocation to mitochondria, which was also reversed by LY294002.

CONCLUSION

DIDS protects cardiomyocytes against STS-induced apoptosis via activating PI3K/Akt signaling pathway, including increasing eNOS phosphorylation and the subsequent NO production and inhibiting Bax translocation.

Authors+Show Affiliations

Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.No 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
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18769044

Citation

Liu, An-Heng, et al. "DIDS Attenuates Staurosporine-induced Cardiomyocyte Apoptosis By PI3K/Akt Signaling Pathway: Activation of eNOS/NO and Inhibition of Bax Translocation." Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, vol. 22, no. 1-4, 2008, pp. 177-86.
Liu AH, Cao YN, Liu HT, et al. DIDS attenuates staurosporine-induced cardiomyocyte apoptosis by PI3K/Akt signaling pathway: activation of eNOS/NO and inhibition of Bax translocation. Cell Physiol Biochem. 2008;22(1-4):177-86.
Liu, A. H., Cao, Y. N., Liu, H. T., Zhang, W. W., Liu, Y., Shi, T. W., Jia, G. L., & Wang, X. M. (2008). DIDS attenuates staurosporine-induced cardiomyocyte apoptosis by PI3K/Akt signaling pathway: activation of eNOS/NO and inhibition of Bax translocation. Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 22(1-4), 177-86. https://doi.org/10.1159/000149795
Liu AH, et al. DIDS Attenuates Staurosporine-induced Cardiomyocyte Apoptosis By PI3K/Akt Signaling Pathway: Activation of eNOS/NO and Inhibition of Bax Translocation. Cell Physiol Biochem. 2008;22(1-4):177-86. PubMed PMID: 18769044.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - DIDS attenuates staurosporine-induced cardiomyocyte apoptosis by PI3K/Akt signaling pathway: activation of eNOS/NO and inhibition of Bax translocation. AU - Liu,An-Heng, AU - Cao,Ya-Nan, AU - Liu,Hong-Tao, AU - Zhang,Wei-Wei, AU - Liu,Yan, AU - Shi,Tang-Wang, AU - Jia,Guo-Liang, AU - Wang,Xiao-Ming, Y1 - 2008/07/25/ PY - 2008/04/08/accepted PY - 2008/9/5/pubmed PY - 2008/11/18/medline PY - 2008/9/5/entrez SP - 177 EP - 86 JF - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JO - Cell Physiol Biochem VL - 22 IS - 1-4 N2 - AIMS: 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), a non-selective chloride channel blocker, has been shown to prevent cell apoptosis, however, the underlying mechanisms remain undefined, thus the present study was to explore whether phosphatidylinositol 3'-kinase (PI3K)/Akt and its downstream molecules are involved in the cytoprotective effect of DIDS. METHODS: Neonatal rat cardiomyocytes were exposed to staurosporine (STS) in the presence or absence of DIDS. Cell viability, apoptosis and expressions of Akt, phospho-Akt (p-Akt), eNOS, phospho-eNOS (p-eNOS), Bcl-2/Bax and nitric oxide (NO) production were determined, and Bax translocation was assessed by double immunofluorescence labeling and Western blotting. RESULTS: DIDS markedly improved cell viability and exerted an anti-apoptotic effect on STS-exposed cardiomyocytes. DIDS resulted in a 2.1-fold increase of p-Akt over control levels, prevented the reduction in eNOS expression and phospho-eNOS levels induced by STS and significantly increased NO production (all P<0.01 vs. STS alone). Treatment with LY294002, a selective PI3K inhibitor, abolished DIDS-induced increases in p-Akt, eNOS, p-eNOS and NO production, and completely abrogated the DIDS-induced anti-apoptotic effect (P<0.01). Treatment with L-NAME, a non-selective NOS inhibitor similarly inhibited the increased NO but only partly abolished protective effects of DIDS (P<0.05). In addition, DIDS effectively inhibited STS-induced Bax translocation to mitochondria, which was also reversed by LY294002. CONCLUSION: DIDS protects cardiomyocytes against STS-induced apoptosis via activating PI3K/Akt signaling pathway, including increasing eNOS phosphorylation and the subsequent NO production and inhibiting Bax translocation. SN - 1421-9778 UR - https://www.unboundmedicine.com/medline/citation/18769044/DIDS_attenuates_staurosporine_induced_cardiomyocyte_apoptosis_by_PI3K/Akt_signaling_pathway:_activation_of_eNOS/NO_and_inhibition_of_Bax_translocation_ L2 - https://www.karger.com?DOI=10.1159/000149795 DB - PRIME DP - Unbound Medicine ER -