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Conference Paper: Calcium signal facilitates the immediate induction of HIF-1α by lipopolysaccharide
Title | Calcium signal facilitates the immediate induction of HIF-1α by lipopolysaccharide |
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Authors | |
Keywords | Periodontics Cell biology Periodontium-gingiva Periodontal disease Host-microbial interactions |
Issue Date | 2010 |
Publisher | Sage Publications, Inc. The Journal's web site is located at http://jdr.sagepub.com/ |
Citation | The 24th IADR-SEA Division Annual Scientific Meeting, Taipei, Taiwan, 19-21 September 2010. In Journal of Dental Research, 2010, v. 89 Spe. Iss. C, abstract no. 130 How to Cite? |
Abstract | Objectives: hypoxia-inducible factor 1 alpha (HIF-1α) is an oxygen-sensitive nuclear transcription factor, which responds to hypoxia or non-hypoxia stimuli by transcribing dozens of downstream genes and participates profoundly in cellular physiology. The regulation of HIF-1α is typically through oxygen-sensitive prolyl hydroxylases (PHDs), which hydroxylize HIF-1α to facilitate its degradation. Other mechanisms include the regulation of the transcription and translation of HIF-1α. We previously reported that lipopolysaccharide (LPS) induces HIF-1α in human primary gingival fibroblasts (HGF). The present study aimed to explore the underlying mechanism via looking into Ca2+/Calmodulin-dependent protein kinase II (CaMKII) and calcineurin pathway. Methods: Human gingival biopsies were harvested from teeth scheduled for extraction because of orthodontic reasons. HGFs were cultured and subjected to LPS treatment only or in combination with actinomycin D (transcription inhibitor), dimethyloxalylglycine (DMOG, PHDs inhibitor), KN-93 (CaMKII inhibitor) or cyclosporin A (calcineurin inhibitor). Realtime RT-PCR, immunoprecipitation and western blotting were performed to detect the transcript and peptide of HIF-1α. Results: Although HIF-1α accumulation could be detected as early as 3 hours after LPS challenge, the transcription level of HIF-1α gene did not increase until after 6 hours. Moreover, when transcription was prohibited by actinomycin D, LPS still induced HIF-1α. Similarly, LPS enhanced the HIF-1α accumulation in DMOG-treated cells, indicating that the LPS effect on HIF-1α may not be through actions of PHDs. However, cyclosporin A and KN-93 dramatically attenuated the LPS-induced HIF-1α accumulation. Conclusions: Ca2+-CaMKII-calcineurin pathway may be essential to the immediate accumulation of HIF-1α in HGFs as a response to LPS challenge. |
Persistent Identifier | http://hdl.handle.net/10722/140035 |
ISSN | 2023 Impact Factor: 5.7 2023 SCImago Journal Rankings: 1.909 |
DC Field | Value | Language |
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dc.contributor.author | Li, JP | - |
dc.contributor.author | Fung, ML | - |
dc.contributor.author | Li, F | - |
dc.contributor.author | Xu, A | - |
dc.contributor.author | Leung, WK | - |
dc.date.accessioned | 2011-09-23T06:05:11Z | - |
dc.date.available | 2011-09-23T06:05:11Z | - |
dc.date.issued | 2010 | - |
dc.identifier.citation | The 24th IADR-SEA Division Annual Scientific Meeting, Taipei, Taiwan, 19-21 September 2010. In Journal of Dental Research, 2010, v. 89 Spe. Iss. C, abstract no. 130 | - |
dc.identifier.issn | 0022-0345 | - |
dc.identifier.uri | http://hdl.handle.net/10722/140035 | - |
dc.description.abstract | Objectives: hypoxia-inducible factor 1 alpha (HIF-1α) is an oxygen-sensitive nuclear transcription factor, which responds to hypoxia or non-hypoxia stimuli by transcribing dozens of downstream genes and participates profoundly in cellular physiology. The regulation of HIF-1α is typically through oxygen-sensitive prolyl hydroxylases (PHDs), which hydroxylize HIF-1α to facilitate its degradation. Other mechanisms include the regulation of the transcription and translation of HIF-1α. We previously reported that lipopolysaccharide (LPS) induces HIF-1α in human primary gingival fibroblasts (HGF). The present study aimed to explore the underlying mechanism via looking into Ca2+/Calmodulin-dependent protein kinase II (CaMKII) and calcineurin pathway. Methods: Human gingival biopsies were harvested from teeth scheduled for extraction because of orthodontic reasons. HGFs were cultured and subjected to LPS treatment only or in combination with actinomycin D (transcription inhibitor), dimethyloxalylglycine (DMOG, PHDs inhibitor), KN-93 (CaMKII inhibitor) or cyclosporin A (calcineurin inhibitor). Realtime RT-PCR, immunoprecipitation and western blotting were performed to detect the transcript and peptide of HIF-1α. Results: Although HIF-1α accumulation could be detected as early as 3 hours after LPS challenge, the transcription level of HIF-1α gene did not increase until after 6 hours. Moreover, when transcription was prohibited by actinomycin D, LPS still induced HIF-1α. Similarly, LPS enhanced the HIF-1α accumulation in DMOG-treated cells, indicating that the LPS effect on HIF-1α may not be through actions of PHDs. However, cyclosporin A and KN-93 dramatically attenuated the LPS-induced HIF-1α accumulation. Conclusions: Ca2+-CaMKII-calcineurin pathway may be essential to the immediate accumulation of HIF-1α in HGFs as a response to LPS challenge. | - |
dc.language | eng | - |
dc.publisher | Sage Publications, Inc. The Journal's web site is located at http://jdr.sagepub.com/ | - |
dc.relation.ispartof | Journal of Dental Research | - |
dc.rights | Journal of Dental Research. Copyright © Sage Publications, Inc. | - |
dc.subject | Periodontics | - |
dc.subject | Cell biology | - |
dc.subject | Periodontium-gingiva | - |
dc.subject | Periodontal disease | - |
dc.subject | Host-microbial interactions | - |
dc.title | Calcium signal facilitates the immediate induction of HIF-1α by lipopolysaccharide | - |
dc.type | Conference_Paper | - |
dc.identifier.email | Fung, ML: fungml@hkucc.hku.hk | - |
dc.identifier.email | Xu, A: amxu@hkucc.hku.hk | - |
dc.identifier.email | Leung, WK: ewkleung@hkucc.hku.hk | - |
dc.identifier.authority | Fung, ML=rp00433 | - |
dc.identifier.authority | Xu, A=rp00485 | - |
dc.identifier.authority | Leung, WK=rp00019 | - |
dc.identifier.hkuros | 195770 | - |
dc.identifier.hkuros | 181632 | - |
dc.identifier.volume | 89 | - |
dc.identifier.issue | Spe. Iss. C | - |
dc.publisher.place | United States | - |
dc.description.other | The 24th Annual Scientific Meeting of the International Association for Dental Research-SEA Division (IADR-SEA 2010) and the 21st Meeting of the South East Asia Association for Dental Education (SEAADE 2010), Taipei, Taiwan, 19-21 September 2010. In Journal of Dental Research, 2010, v. 89 n. Special Issue C, abstract no. 130 (SEA Division) | - |
dc.identifier.issnl | 0022-0345 | - |