Ironjustic
Wed, Mar-12-08, 17:15
NEUROPROTECTIVE ACTIONS OF DEFERIPRONE IN CULTURED CORTICAL
NEURONES AND SHSY5Y CELLS. [JOURNAL ARTICLE] J Neurochem
2008 Mar 9. Molina-Holgado F, Gaeta A, Francis PT, Williams
RJ, Hider RC
Alzheimer's disease (AD) is a common neurodegenerative
disorder, but the initiating molecular processes contributing
to neuronal death are not well understood. AD is associated
with elevated soluble and aggregated forms of amyloid beta
(Abeta) and with oxidative stress. Furthermore, there is
increasing evidence for a detrimental role of iron in the
pathogenic process. In this context iron chelation by
compounds such as 3-hydroxypyridin-4-one, deferiprone
(Ferriprox(TM)) may have potential neuroprotective effects. We
have evaluated the possible neuroprotective actions of
deferiprone against a range of AD- relevant insults including
ferric iron, H(2)O(2) and Abeta in primary mouse cortical
neurones. We have investigated the possible neuroprotective
actions of deferiprone (1, 3, 10, 30 or 100 muM) in primary
neuronal cultures following exposure to ferric iron (FeNTA; 3
and 10 muM), H(2)O(2) (100 muM) or Abeta1-40 (3, 10 and 20
muM). Cultures were treated with deferiprone or vehicle either
immediately or up to 6h after the insult in a 24 well plate
format. In order to elucidate a possible neuroprotective
action of deferiprone against Parkinson's disease (PD)
relevant insults another group of experiments were performed
in the human neuroblastoma catecholaminergic SHSY-5Y cell
line. SHSY-5Y cells were treated with
1-methyl-4-phenylpyridinium (MPP(+)) iodide, the active
metabolite of the dopaminergic neurotoxin MPTP and the
neuroprotective actions of deferiprone evaluated. Cytotoxicity
was assessed at 24h by LDH release, MTT turnover (FeNTA and
hydrogen peroxide) and morphometric analysis of cell viability
by Hoechst 33324/Propidium iodide (FeNTA, Abeta and MPP(+)) or
6-CFDA and annexin V-Cy3 (Abeta). The present study
demonstrates that deferiprone protects against FeNTA, hydrogen
peroxide, MPP(+) and Abeta1-40- induced neuronal cell death in
vitro, which is consistent with previous in vitro and in vivo
studies that have demonstrated similar protection with other
iron chelators.
Journal of neurochemistry [J Neurochem]
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-------------------
Who loves ya. Tom
Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com
Man Is A Herbivore! http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING http://tinyurl.com/zk9fk
NEURONES AND SHSY5Y CELLS. [JOURNAL ARTICLE] J Neurochem
2008 Mar 9. Molina-Holgado F, Gaeta A, Francis PT, Williams
RJ, Hider RC
Alzheimer's disease (AD) is a common neurodegenerative
disorder, but the initiating molecular processes contributing
to neuronal death are not well understood. AD is associated
with elevated soluble and aggregated forms of amyloid beta
(Abeta) and with oxidative stress. Furthermore, there is
increasing evidence for a detrimental role of iron in the
pathogenic process. In this context iron chelation by
compounds such as 3-hydroxypyridin-4-one, deferiprone
(Ferriprox(TM)) may have potential neuroprotective effects. We
have evaluated the possible neuroprotective actions of
deferiprone against a range of AD- relevant insults including
ferric iron, H(2)O(2) and Abeta in primary mouse cortical
neurones. We have investigated the possible neuroprotective
actions of deferiprone (1, 3, 10, 30 or 100 muM) in primary
neuronal cultures following exposure to ferric iron (FeNTA; 3
and 10 muM), H(2)O(2) (100 muM) or Abeta1-40 (3, 10 and 20
muM). Cultures were treated with deferiprone or vehicle either
immediately or up to 6h after the insult in a 24 well plate
format. In order to elucidate a possible neuroprotective
action of deferiprone against Parkinson's disease (PD)
relevant insults another group of experiments were performed
in the human neuroblastoma catecholaminergic SHSY-5Y cell
line. SHSY-5Y cells were treated with
1-methyl-4-phenylpyridinium (MPP(+)) iodide, the active
metabolite of the dopaminergic neurotoxin MPTP and the
neuroprotective actions of deferiprone evaluated. Cytotoxicity
was assessed at 24h by LDH release, MTT turnover (FeNTA and
hydrogen peroxide) and morphometric analysis of cell viability
by Hoechst 33324/Propidium iodide (FeNTA, Abeta and MPP(+)) or
6-CFDA and annexin V-Cy3 (Abeta). The present study
demonstrates that deferiprone protects against FeNTA, hydrogen
peroxide, MPP(+) and Abeta1-40- induced neuronal cell death in
vitro, which is consistent with previous in vitro and in vivo
studies that have demonstrated similar protection with other
iron chelators.
Journal of neurochemistry [J Neurochem]
--------------------------------------------------------------
-------------------
Who loves ya. Tom
Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com
Man Is A Herbivore! http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING http://tinyurl.com/zk9fk