Candesartan prevents angiotensin II-induced facilitation of hypoxic neuronal damage through PKC delta inhibition
(2005) In Brain Research. Molecular Brain Research 135(1-2). p.134-140- Abstract
- To investigate the role of protein kinase C delta (PKC delta) in angiotensin II-induced facilitation mechanisms of hypoxic neuronal damage and whether candesartan, an AT1 receptor antagonist, can suppress these mechanisms, we performed in vitro experiments which were free from vascular components using PC12 cells under hypoxic (12 h)/reoxygenation (0-48 h) conditions. Angiotensin II apparently increased the basal expression level of PKC delta phosphorylated at Ser(643) before hypoxia, promoted the cleavage of PKC delta to its catalytic fragment, and fostered the progression of DNA fragmentation after hypoxia. Candesartan inhibited both phosphorylation and cleavage of PKC delta and suppressed the angiotensin II-induced facilitation of DNA... (More)
- To investigate the role of protein kinase C delta (PKC delta) in angiotensin II-induced facilitation mechanisms of hypoxic neuronal damage and whether candesartan, an AT1 receptor antagonist, can suppress these mechanisms, we performed in vitro experiments which were free from vascular components using PC12 cells under hypoxic (12 h)/reoxygenation (0-48 h) conditions. Angiotensin II apparently increased the basal expression level of PKC delta phosphorylated at Ser(643) before hypoxia, promoted the cleavage of PKC delta to its catalytic fragment, and fostered the progression of DNA fragmentation after hypoxia. Candesartan inhibited both phosphorylation and cleavage of PKC delta and suppressed the angiotensin II-induced facilitation of DNA fragmentation under hypoxic/reoxygenation conditions. However, PD123319, an AT2 receptor antagonist, influenced neither PKC delta nor the angiotensin II-induced facilitation of DNA fragmentation. Furthermore, in PC12 cells expressing the ATP-binding mutant of PKC delta (PKC delta(K376R)) acting as a dominant-negative protein, both phosphorylation and cleavage of PKC delta were attenuated and DNA fragmentation was markedly suppressed regardless of the presence of angiotensin II. These findings suggest that angiotensin II-induced facilitation of DNA fragmentation under hypoxic conditions is mediated by PKC delta, and the mechanisms can be suppressed by the candesartan mediated blockade of the AT1 receptor. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/240007
- author
- Utsugisawa, K ; Nagane, Y ; Utsugisawa, Taiju LU ; Obara, D and Terayama, Y
- organization
- publishing date
- 2005
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- PC12 cell, hypoxia, DNA fragmentation, angiotensin II, AT1 receptor, protein kinase C delta
- in
- Brain Research. Molecular Brain Research
- volume
- 135
- issue
- 1-2
- pages
- 134 - 140
- publisher
- Elsevier
- external identifiers
-
- wos:000229206100014
- pmid:15857676
- scopus:18044374121
- ISSN
- 0169-328X
- DOI
- 10.1016/j.molbrainres.2004.12.004
- language
- English
- LU publication?
- yes
- id
- 13a25633-bfd7-4f9a-8bd9-541d505b5d00 (old id 240007)
- date added to LUP
- 2016-04-01 16:55:29
- date last changed
- 2022-01-28 23:06:37
@article{13a25633-bfd7-4f9a-8bd9-541d505b5d00,
abstract = {{To investigate the role of protein kinase C delta (PKC delta) in angiotensin II-induced facilitation mechanisms of hypoxic neuronal damage and whether candesartan, an AT1 receptor antagonist, can suppress these mechanisms, we performed in vitro experiments which were free from vascular components using PC12 cells under hypoxic (12 h)/reoxygenation (0-48 h) conditions. Angiotensin II apparently increased the basal expression level of PKC delta phosphorylated at Ser(643) before hypoxia, promoted the cleavage of PKC delta to its catalytic fragment, and fostered the progression of DNA fragmentation after hypoxia. Candesartan inhibited both phosphorylation and cleavage of PKC delta and suppressed the angiotensin II-induced facilitation of DNA fragmentation under hypoxic/reoxygenation conditions. However, PD123319, an AT2 receptor antagonist, influenced neither PKC delta nor the angiotensin II-induced facilitation of DNA fragmentation. Furthermore, in PC12 cells expressing the ATP-binding mutant of PKC delta (PKC delta(K376R)) acting as a dominant-negative protein, both phosphorylation and cleavage of PKC delta were attenuated and DNA fragmentation was markedly suppressed regardless of the presence of angiotensin II. These findings suggest that angiotensin II-induced facilitation of DNA fragmentation under hypoxic conditions is mediated by PKC delta, and the mechanisms can be suppressed by the candesartan mediated blockade of the AT1 receptor.}},
author = {{Utsugisawa, K and Nagane, Y and Utsugisawa, Taiju and Obara, D and Terayama, Y}},
issn = {{0169-328X}},
keywords = {{PC12 cell; hypoxia; DNA fragmentation; angiotensin II; AT1 receptor; protein kinase C delta}},
language = {{eng}},
number = {{1-2}},
pages = {{134--140}},
publisher = {{Elsevier}},
series = {{Brain Research. Molecular Brain Research}},
title = {{Candesartan prevents angiotensin II-induced facilitation of hypoxic neuronal damage through PKC delta inhibition}},
url = {{http://dx.doi.org/10.1016/j.molbrainres.2004.12.004}},
doi = {{10.1016/j.molbrainres.2004.12.004}},
volume = {{135}},
year = {{2005}},
}