Formation of electrophilic oxidation products from mitochondrial cardiolipin in vitro and in vivo in the context of apoptosis and atherosclerosis

Autor: Jianhong Lu, Huiyong Yin, Huiqin Zhong, Lin Xia, Mingjiang Zhu
Rok vydání: 2014
Předmět:
EAA-CL
epoxyalcohol-aldehyde-CL
Arteriosclerosis
BHT
butylate hydroxytoluene
Clinical Biochemistry
Apoptosis
M4CL
tetramyristeoyl cardiolipin
Mitochondrion
Biochemistry
Mass Spectrometry
Lipid peroxidation
chemistry.chemical_compound
Mice
ALDH2
aldehyde dehydrogenase-2
Cardiolipin
PUFAs
Polyunsaturated fatty acids
LC–MS
liquid chromatography–mass spectrometry
HODE
hydroxyoctadienoic acid
lcsh:QH301-705.5
Chromatography
High Pressure Liquid
Mice
Knockout
lcsh:R5-920
biology
Chemistry
Cytochrome c
KODE
keto-octadecadienoic acid
4-HNE
4-hydroxy-nonena
Prdx3/Prx3
peroxiredoxin 3
CL
cardiolipin cyt c cytochrome c
Mitochondria
Liver
PHGPX
hospholipid hydroperoxide glutathione peroxidase
Epoxyalcohol-aldehyde-CL (EAA-CL)
4-ONE
4-oxo-2-nonenal
H2O2
hydrogen peroxide
lcsh:Medicine (General)
Oxidation-Reduction
Liquid chromatography–mass spectrometry (LC–MS)
BH3 Interacting Domain Death Agonist Protein
Research Paper
Cardiolipins
ETC
electron transport chain
HpODE
hydroperoxyoctadecadienoic acid
Context (language use)
L3OCL
trilinoleoyl oleoyl cardiolipin
Diet
High-Fat
L4CL
tetralinoleoyl cardiolipin
LDLR −/−
low density lipoprotein receptor knockout
ESI
electrospray
ROS
reactive oxygen species
Animals
ALDH2
Acetaminophen
LA
linoleic acid
Organic Chemistry
ApAP
acetaminophen
Atherosclerosis
lcsh:Biology (General)
Receptors
LDL
LDL receptor
4-hydroxy-2-nonenal (4-HNE)
biology.protein
MRM
multiple reaction monitoring
Zdroj: Redox Biology
Redox Biology, Vol 2, Iss C, Pp 878-883 (2014)
ISSN: 2213-2317
Popis: Emerging evidence indicates that mitochondrial cardiolipins (CL) are prone to free radical oxidation and this process appears to be intimately associated with multiple biological functions of mitochondria. Our previous work demonstrated that a significant amount of potent lipid electrophiles including 4-hydroxy-nonenal (4-HNE) was generated from CL oxidation through a novel chemical mechanism. Here we provide further evidence that a characteristic class of CL oxidation products, epoxyalcohol-aldehyde-CL (EAA-CL), is formed through this novel mechanism in isolated mice liver mitochondria when treated with the pro-apoptotic protein t-Bid to induce cyt c release. Generation of these oxidation products are dose-dependently attenuated by a peroxidase inhibitor acetaminophen (ApAP). Using a mouse model of atherosclerosis, we detected significant amount of these CL oxidation products in liver tissue of low density lipoprotein receptor knockout (LDLR −/−) mice after Western diet feeding. Our studies highlight the importance of lipid electrophiles formation from CL oxidation in the settings of apoptosis and atherosclerosis as inhibition of CL oxidation and lipid electrophiles formation may have potential therapeutic value in diseases linked to oxidant stress and mitochondrial dysfunctions.
Highlights • 4-HNE and other electrophilic lipids are formed from mitochondrial cardiolipin. • Novel electrophilic oxidation products EAA-CL were identified in vitro and in vivo. • Level of EAA-CL in liver tissue of LDLR −/− mice is higher with Western diet feeding. • ApAP dose-dependently inhibits EAA-CL formation during t-Bid induced cyt c release. • CL electrophilic lipid formation is important in apoptosis and atherosclerosis.
Graphical Abstract
Databáze: OpenAIRE
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