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Apoptosis signal-regulating kinase 1 (ASK1) and HIF-1 alpha protein are essential factors for nitric oxide-dependent accumulation of p53 in THP-1 human myeloid macrophages

Jawahir, Mohammad, Nicholas, Sally A., Coughlan, Karen, Sumbayev, Vadim V. (2008) Apoptosis signal-regulating kinase 1 (ASK1) and HIF-1 alpha protein are essential factors for nitric oxide-dependent accumulation of p53 in THP-1 human myeloid macrophages. Apoptosis, 13 (12). pp. 1410-1416. ISSN 1360-8185. (doi:10.1007/s10495-008-0267-9) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:15722)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided.
Official URL:
http://dx.doi.org/10.1007/s10495-008-0267-9

Abstract

Nitric oxide (NO) is a reactive secondary mediator, which has been found to participate in cell cycle regulation and apoptosis in myeloid macrophages, the key effectors of inflammatory and innate immune responses. However, the molecular mechanisms of nitric oxide-induced death of myeloid macrophages are not well understood. In this study we have found that NO derived from S-nitrosoglutathione (GSNO) activates ASK1 in THP-1 human myeloid macrophages in a concentration and time-dependent manner. It also induces accumulation of HIF-1 alpha protein in a concentration-dependent manner, which peaks at 4 h of exposure to 1 mM GSNO. GSNO does not affect the level of HIF-1 alpha mRNA as detected by the RT-PCR. In addition, GSNO was found to induce accumulation of p53 in normal but not HIF-1 alpha knockdown THP-1 cells, where expression of this protein was silenced by specific siRNA. It has also been found that GSNO-mediated accumulation of p53 depends on activation of ASK1 since no GSNO-induced p53 stabilisation was observed in THP-1 cells transfected with dominant-negative form of this kinase. However, in both HIF-1 alpha knockdown THP-1 cells and those transfected with the dominant-negative form of ASK1, GSNO was able to induce cell death as detected by the MTS cell viability assay leading to an increase in release of LDH.

Item Type: Article
DOI/Identification number: 10.1007/s10495-008-0267-9
Uncontrolled keywords: Apoptosis; Nitric oxide; Hypoxia; P53
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User: Jane Griffiths
Date Deposited: 22 Apr 2009 13:40 UTC
Last Modified: 16 Nov 2021 09:53 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/15722 (The current URI for this page, for reference purposes)

University of Kent Author Information

Coughlan, Karen.

Creator's ORCID:
CReDIT Contributor Roles:

Sumbayev, Vadim V..

Creator's ORCID: https://orcid.org/0000-0002-9404-5626
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