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Article: Inhibition of HIV-1 gp120-induced apoptosis in neuroblastoma SK-N-SH cells by an antisense oligodeoxynucleotide against p53

TitleInhibition of HIV-1 gp120-induced apoptosis in neuroblastoma SK-N-SH cells by an antisense oligodeoxynucleotide against p53
Authors
Issue Date1998
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.AIDSonline.com
Citation
Aids, 1998, v. 12 n. 4, p. 349-354 How to Cite?
AbstractObjectives: This study examines the cytotoxicity potential and the mechanism of toxicity of the HIV-1 gp120 on human neuroblastoma cells. Design: Previous data from our group have suggested that the HIV-1 envelope protein gp120 promotes the secretion of tumor necrosis factor-α and other factors by astrocytes and microglial cells present in primary human brain cell cultures, thereby contributing to the injury of neurons in these cultures. This study investigates the cytotoxicity potential and the mechanism of toxicity of gp120 on human neuroblastoma cells. Methods: SK-N-SH cells were treated with HIV-1 gp120, and was followed by in situ DNA fragmentation staining and small molecular weight DNA extraction studies to ascertain the induction of apoptosis by gp120 in these cells. To evaluate a potential role of the growth suppressor gene p53, gp120-treated SK-N-SH cells were subjected to reverse transcription polymerase chain reaction (RT-PCR) and Western blot analyses for the induction of p53. An antisense oligodeoxynucleotide against p53 was used to investigate the role of p53 in the gp120-induced apoptosis in these cells. Results: Data from T7 DNA polymerase staining and small molecular weight DNA extraction studies demonstrated that gp120-induced DNA breakage in SK-N-SH cells with fragmentation patterns characteristic of apoptosis. RT-PCR and Western blot analyses revealed that the gp120-mediated induction of apoptosis was dependent on a gp120-induced and gp120-sustained upregulation of p53. The induction of p53 by gp120 was specific, since an antibody against gp120 prevented both the induction of p53 and subsequent apoptosis in SK-N-SH cells. The critical role of p53 was further illustrated by the effectiveness of a p53 antisense oligodeoxynucleotide to inhibit the gp120-induced apoptosis. As a control, the apoptosis-inducing potential of gp120 on SK-N-SH cells was not seen in the HIV-1 Gag proteins even when used at up to 5 nM. Conclusions: These results established that HIV-1 gp120 is potentially cytotoxic to human neuronal cells through the induction of p53, which may eventually lead to induction of apoptosis.
Persistent Identifierhttp://hdl.handle.net/10722/170294
ISSN
2015 Impact Factor: 4.407
2015 SCImago Journal Rankings: 3.112
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYeung, MCen_US
dc.contributor.authorGeertsma, Fen_US
dc.contributor.authorLiu, Jen_US
dc.contributor.authorLau, ASen_US
dc.date.accessioned2012-10-30T06:07:17Z-
dc.date.available2012-10-30T06:07:17Z-
dc.date.issued1998en_US
dc.identifier.citationAids, 1998, v. 12 n. 4, p. 349-354en_US
dc.identifier.issn0269-9370en_US
dc.identifier.urihttp://hdl.handle.net/10722/170294-
dc.description.abstractObjectives: This study examines the cytotoxicity potential and the mechanism of toxicity of the HIV-1 gp120 on human neuroblastoma cells. Design: Previous data from our group have suggested that the HIV-1 envelope protein gp120 promotes the secretion of tumor necrosis factor-α and other factors by astrocytes and microglial cells present in primary human brain cell cultures, thereby contributing to the injury of neurons in these cultures. This study investigates the cytotoxicity potential and the mechanism of toxicity of gp120 on human neuroblastoma cells. Methods: SK-N-SH cells were treated with HIV-1 gp120, and was followed by in situ DNA fragmentation staining and small molecular weight DNA extraction studies to ascertain the induction of apoptosis by gp120 in these cells. To evaluate a potential role of the growth suppressor gene p53, gp120-treated SK-N-SH cells were subjected to reverse transcription polymerase chain reaction (RT-PCR) and Western blot analyses for the induction of p53. An antisense oligodeoxynucleotide against p53 was used to investigate the role of p53 in the gp120-induced apoptosis in these cells. Results: Data from T7 DNA polymerase staining and small molecular weight DNA extraction studies demonstrated that gp120-induced DNA breakage in SK-N-SH cells with fragmentation patterns characteristic of apoptosis. RT-PCR and Western blot analyses revealed that the gp120-mediated induction of apoptosis was dependent on a gp120-induced and gp120-sustained upregulation of p53. The induction of p53 by gp120 was specific, since an antibody against gp120 prevented both the induction of p53 and subsequent apoptosis in SK-N-SH cells. The critical role of p53 was further illustrated by the effectiveness of a p53 antisense oligodeoxynucleotide to inhibit the gp120-induced apoptosis. As a control, the apoptosis-inducing potential of gp120 on SK-N-SH cells was not seen in the HIV-1 Gag proteins even when used at up to 5 nM. Conclusions: These results established that HIV-1 gp120 is potentially cytotoxic to human neuronal cells through the induction of p53, which may eventually lead to induction of apoptosis.en_US
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.AIDSonline.comen_US
dc.relation.ispartofAIDSen_US
dc.subject.meshApoptosisen_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshDna Fragmentationen_US
dc.subject.meshGenes, P53en_US
dc.subject.meshHiv Envelope Protein Gp120 - Pharmacologyen_US
dc.subject.meshHumansen_US
dc.subject.meshNeuroblastomaen_US
dc.subject.meshOligonucleotides, Antisense - Genetics - Pharmacologyen_US
dc.subject.meshPolymerase Chain Reactionen_US
dc.subject.meshTranscription, Geneticen_US
dc.subject.meshTumor Cells, Cultureden_US
dc.subject.meshUp-Regulationen_US
dc.titleInhibition of HIV-1 gp120-induced apoptosis in neuroblastoma SK-N-SH cells by an antisense oligodeoxynucleotide against p53en_US
dc.typeArticleen_US
dc.identifier.emailLau, AS:asylau@hku.hken_US
dc.identifier.authorityLau, AS=rp00474en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1097/00002030-199804000-00002-
dc.identifier.pmid9520163-
dc.identifier.scopuseid_2-s2.0-0032485244en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0032485244&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume12en_US
dc.identifier.issue4en_US
dc.identifier.spage349en_US
dc.identifier.epage354en_US
dc.identifier.isiWOS:000072037800003-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridYeung, MC=7101861664en_US
dc.identifier.scopusauthoridGeertsma, F=6506271158en_US
dc.identifier.scopusauthoridLiu, J=36071959600en_US
dc.identifier.scopusauthoridLau, AS=7202626202en_US

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