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Article: bcl-2 protects HL-60 cells from apoptosis by stabilizing their intracellular calcium pools

Titlebcl-2 protects HL-60 cells from apoptosis by stabilizing their intracellular calcium pools
Authors
Issue Date2001
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/lifescie
Citation
Life Sciences, 2001, v. 68 n. 25, p. 2873-2883 How to Cite?
Abstractbcl-2 has been shown to enhance cell survival by inhibiting apoptosis induced under different circumstances. In this study we investigated the effects of bcl-2 overexpression on the homeostasis of subcellular organelles such as ER and mitochondria. In our study, HL-60/bcl-2 and control HL-60/neo cells were obtained by transfection of bcl-2 cDNA or the neomycin-resistant gene, respectively. Apoptosis was evaluated by both DNA fragmentation and flow cytometry qualitatively and quantitatively, and the intracellular calcium by Fura-2/AM. Thapsigargin (TG), a highly specific inhibitor of the ER-associated Ca2+ pump, and Br-A23187, a calcium ionophore, were used in this study. Our results showed that overexpression of bcl-2 significantly blocked TG- and Br-A23187-induced apoptosis in calcium containing buffer. Measurement of intracellular calcium showed that bcl-2 overexpression could reduce sustained elevation of cytosolic Ca2+ induced by these agents. However, in calcium-free medium, bcl-2 overexpression maintained Ca2+ uptake in ER of both TG- and Br-A23187-treated cells. Moreover, the depletion of Ca2+ by EGTA enhanced TG- and Br-A23187-induced apoptosis, and reduced the anti-apoptotic action of bcl-2, suggesting that cytosolic Ca2+ elevation may be required for optimal ER pool refilling. These findings suggest that bcl-2 facilitates and maintains the replenishment of Ca2+ in intracellular stores and, as a result, influences the intracellular calcium, thus protecting the cells from death. In addition, there were no cytochrome c release from mitochondria into the cytosol in TG- and Br-A23187- induced apoptosis, suggesting that cytochrome c release is not a universal phenomenon in the apoptotic process.
Persistent Identifierhttp://hdl.handle.net/10722/224097
ISSN
2015 Impact Factor: 2.685
2015 SCImago Journal Rankings: 1.056

 

DC FieldValueLanguage
dc.contributor.authorZhang, QH-
dc.contributor.authorSheng, HP-
dc.contributor.authorLoh, TT-
dc.date.accessioned2016-03-23T07:17:31Z-
dc.date.available2016-03-23T07:17:31Z-
dc.date.issued2001-
dc.identifier.citationLife Sciences, 2001, v. 68 n. 25, p. 2873-2883-
dc.identifier.issn0024-3205-
dc.identifier.urihttp://hdl.handle.net/10722/224097-
dc.description.abstractbcl-2 has been shown to enhance cell survival by inhibiting apoptosis induced under different circumstances. In this study we investigated the effects of bcl-2 overexpression on the homeostasis of subcellular organelles such as ER and mitochondria. In our study, HL-60/bcl-2 and control HL-60/neo cells were obtained by transfection of bcl-2 cDNA or the neomycin-resistant gene, respectively. Apoptosis was evaluated by both DNA fragmentation and flow cytometry qualitatively and quantitatively, and the intracellular calcium by Fura-2/AM. Thapsigargin (TG), a highly specific inhibitor of the ER-associated Ca2+ pump, and Br-A23187, a calcium ionophore, were used in this study. Our results showed that overexpression of bcl-2 significantly blocked TG- and Br-A23187-induced apoptosis in calcium containing buffer. Measurement of intracellular calcium showed that bcl-2 overexpression could reduce sustained elevation of cytosolic Ca2+ induced by these agents. However, in calcium-free medium, bcl-2 overexpression maintained Ca2+ uptake in ER of both TG- and Br-A23187-treated cells. Moreover, the depletion of Ca2+ by EGTA enhanced TG- and Br-A23187-induced apoptosis, and reduced the anti-apoptotic action of bcl-2, suggesting that cytosolic Ca2+ elevation may be required for optimal ER pool refilling. These findings suggest that bcl-2 facilitates and maintains the replenishment of Ca2+ in intracellular stores and, as a result, influences the intracellular calcium, thus protecting the cells from death. In addition, there were no cytochrome c release from mitochondria into the cytosol in TG- and Br-A23187- induced apoptosis, suggesting that cytochrome c release is not a universal phenomenon in the apoptotic process.-
dc.languageeng-
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/lifescie-
dc.relation.ispartofLife Sciences-
dc.rightsPosting accepted manuscript (postprint): © <year>. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/-
dc.subject.meshApoptosis-
dc.subject.meshCalcium - deficiency - metabolism-
dc.subject.meshHL-60 Cells - drug effects - metabolism-
dc.subject.meshProto-Oncogene Proteins c-bcl-2 - biosynthesis - physiology-
dc.subject.meshThapsigargin - pharmacology-
dc.titlebcl-2 protects HL-60 cells from apoptosis by stabilizing their intracellular calcium pools-
dc.typeArticle-
dc.identifier.emailSheng, HP: hpsheng@hkucc.hku.hk-
dc.identifier.emailLoh, TT: ttloh@hkucc.hku.hk-
dc.identifier.doi10.1016/S0024-3205(01)01073-6-
dc.identifier.pmid11432453-
dc.identifier.hkuros60114-
dc.identifier.volume68-
dc.identifier.issue25-
dc.identifier.spage2873-
dc.identifier.epage2883-
dc.publisher.placeUnited States-

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