scholarly journals Cotton cytochrome P450 CYP82D regulates systemic cell death by modulating the octadecanoid pathway

2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Longqing Sun ◽  
Longfu Zhu ◽  
Li Xu ◽  
Daojun Yuan ◽  
Ling Min ◽  
...  
Keyword(s):  
Cell Death ◽  
Cytochrome P450 ◽  
Octadecanoid Pathway

scholarly journals Drugs Repurposed as Antiferroptosis Agents Suppress Organ Damage, Including AKI, by Functioning as Lipid Peroxyl Radical Scavengers

2019 ◽  
Vol 31 (2) ◽  
pp. 280-296 ◽  
Author(s):  
Eikan Mishima ◽  
Emiko Sato ◽  
Junya Ito ◽  
Ken-ichi Yamada ◽  
Chitose Suzuki ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Cell Death ◽  
Cytochrome P450 ◽  
Liver Injury ◽  
Peroxyl Radical ◽  
Organ Damage ◽  
Peroxyl Radicals ◽  
Radical Scavengers ◽  
Lipid Peroxyl Radicals ◽  
Elevated Lipid

BackgroundFerroptosis, nonapoptotic cell death mediated by free radical reactions and driven by the oxidative degradation of lipids, is a therapeutic target because of its role in organ damage, including AKI. Ferroptosis-causing radicals that are targeted by ferroptosis suppressors have not been unequivocally identified. Because certain cytochrome P450 substrate drugs can prevent lipid peroxidation via obscure mechanisms, we evaluated their antiferroptotic potential and used them to identify ferroptosis-causing radicals.MethodsUsing a cell-based assay, we screened cytochrome P450 substrate compounds to identify drugs with antiferroptotic activity and investigated the underlying mechanism. To evaluate radical-scavenging activity, we used electron paramagnetic resonance–spin trapping methods and a fluorescence probe for lipid radicals, NBD-Pen, that we had developed. We then assessed the therapeutic potency of these drugs in mouse models of cisplatin-induced AKI and LPS/galactosamine-induced liver injury.ResultsWe identified various US Food and Drug Administration–approved drugs and hormones that have antiferroptotic properties, including rifampicin, promethazine, omeprazole, indole-3-carbinol, carvedilol, propranolol, estradiol, and thyroid hormones. The antiferroptotic drug effects were closely associated with the scavenging of lipid peroxyl radicals but not significantly related to interactions with other radicals. The elevated lipid peroxyl radical levels were associated with ferroptosis onset, and known ferroptosis suppressors, such as ferrostatin-1, also functioned as lipid peroxyl radical scavengers. The drugs exerted antiferroptotic activities in various cell types, including tubules, podocytes, and renal fibroblasts. Moreover, in mice, the drugs ameliorated AKI and liver injury, with suppression of tissue lipid peroxidation and decreased cell death.ConclusionsAlthough elevated lipid peroxyl radical levels can trigger ferroptosis onset, some drugs that scavenge lipid peroxyl radicals can help control ferroptosis-related disorders, including AKI.

Oxidative stress and cell death induction by amitraz and its metabolite BTS-27271 mediated through cytochrome P450 and NRF2 pathway alteration in primary hippocampal cell

2019 ◽  
Vol 129 ◽  
pp. 87-96 ◽  
Author(s):  
Paula Moyano ◽  
Matilde Ruiz ◽  
José Manuel García ◽  
María Teresa Frejo ◽  
María José Anadon Baselga ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Cytochrome P450 ◽  
Nrf2 Pathway ◽  
Hippocampal Cell

Inhibition of cytochrome P450 2J2 by tanshinone IIA induces apoptotic cell death in hepatocellular carcinoma HepG2 cells

2015 ◽  
Vol 764 ◽  
pp. 480-488 ◽  
Author(s):  
Yu Jin Jeon ◽  
Joong Sun Kim ◽  
Geun Hye Hwang ◽  
Zhexue Wu ◽  
Ho Jae Han ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Cytochrome P450 ◽  
Hepg2 Cells ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Tanshinone Iia

scholarly journals Necrotic, rather than apoptotic, cell death caused by cytochrome P450–activated ifosfamide

2001 ◽  
Vol 8 (3) ◽  
pp. 220-230 ◽  
Author(s):  
Peter Karle ◽  
Matthias Renner ◽  
Brian Salmons ◽  
Walter H Günzburg
Keyword(s):  
Cell Death ◽  
Cytochrome P450 ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death

scholarly journals Role of Cell Death in Toxicology: Does It Matter How Cells Die?

2019 ◽  
Vol 59 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Sten Orrenius
Keyword(s):  
Cell Death ◽  
Cytochrome P450 ◽  
Drug Metabolism ◽  
Liver Microsomes ◽  
Rat Hepatocytes ◽  
Rat Liver Microsomes ◽  
Research Activity ◽  
Isolated Rat Hepatocytes ◽  
Cellular Defense ◽  
Toxic Injury

My research activity started with studies on drug metabolism in rat liver microsomes in the early 1960s. The CO-binding pigment (cytochrome P450) had been discovered a few years earlier and was subsequently found to be involved in steroid hydroxylation in adrenal cortex microsomes. Our early studies suggested that it also participated in the oxidative demethylation of drugs catalyzed by liver microsomes, and that prior treatment of the animals with phenobarbital caused increased levels of the hemoprotein in the liver, and similarly enhanced rates of drug metabolism. Subsequent studies of cytochrome P450-mediated metabolism of toxic drugs in freshly isolated rat hepatocytes characterized critical cellular defense systems and identified mechanisms by which accumulating toxic metabolites could damage and kill the cells. These studies revealed that multiple types of cell death could result from the toxic injury, and that it is important to know which type of cell death results from the toxic injury.

Methyl jasmonate-induced cell death in grapevine requires both lipoxygenase activity and functional octadecanoid biosynthetic pathway

Biologia ◽  
2013 ◽  
Vol 68 (5) ◽  
Author(s):  
Vladimír Repka ◽  
Mária Čarná ◽  
Ján Pavlovkin
Keyword(s):  
Cell Death ◽  
Methyl Jasmonate ◽  
Biosynthetic Pathway ◽  
Cultured Cells ◽  
De Novo ◽  
Metabolic Inhibitors ◽  
Vitis Vinifera L ◽  
Lipoxygenase Inhibitor ◽  
Octadecanoid Pathway ◽  
Induced Signal

AbstractGrapevine (Vitis vinifera L., cv. Limberger) leaf tissues and suspension-cultured cells were induced to undergo programmed cell death (PCD) by exogenously added methyl jasmonate (MeJA). The elicitor signaling pathway involved in MeJA-induced PCD was further investigated using pharmacological, biochemical and histological approaches. Pharmacological dissection of the early events preceding the execution of MeJA-triggered PCD indicated that this process strongly depends on both, de novo protein and mRNA synthesis. Treatment of leaf discs and cell suspensions with lipase inhibitor Ebelactone B and specific lipoxygenase inhibitor Phenidone blocked MeJA-induced PCD. These results suggest that some chloroplast membrane-derived compound(s) is required for MeJA-induced PCD in grapevine. The progression of MeJAtriggered PCD may be further inhibited by the use of metabolic inhibitors of key enzymes of octadecanoid biosynthesis including AOS, AOC, and OPR indicating that the functional jasmonate biosynthetic pathway is an integral part of the MeJA-induced signal transduction cascade that results in the coordinate expression of events leading to PCD. Finally, the activation of the octadecanoid pathway, as a critical point in MeJA-induced PCD, was independently demonstrated with cellulysin, a macromolecular elicitor acting via octadecanoid signaling. The cellulysin was shown to be a very potent enhancer of MeJA-triggered PCD in grapevine cells.

scholarly journals Mutations in a barley cytochrome P450 gene enhances pathogen induced programmed cell death and cutin layer instability

PLoS Genetics ◽  
2021 ◽  
Vol 17 (12) ◽  
pp. e1009473
Author(s):  
Gazala Ameen ◽  
Shyam Solanki ◽  
Lauren Sager-Bittara ◽  
Jonathan Richards ◽  
Prabin Tamang ◽  
...  
Keyword(s):  
Cell Death ◽  
Cytochrome P450 ◽  
Programmed Cell Death ◽  
Plant Immunity ◽  
Susceptibility Gene ◽  
Bipolaris Sorokiniana ◽  
Post Inoculation ◽  
Cytochrome P450 Gene ◽  
P450 Gene ◽  
Pigmented Lesions

Disease lesion mimic mutants (DLMMs) are characterized by the spontaneous development of necrotic spots with various phenotypes designated as necrotic (nec) mutants in barley. The nec mutants were traditionally considered to have aberrant regulation of programmed cell death (PCD) pathways, which have roles in plant immunity and development. Most barley nec3 mutants express cream to orange necrotic lesions contrasting them from typical spontaneous DLMMs that develop dark pigmented lesions indicative of serotonin/phenolics deposition. Barley nec3 mutants grown under sterile conditions did not exhibit necrotic phenotypes until inoculated with adapted pathogens, suggesting that they are not typical DLMMs. The F2 progeny of a cross between nec3-γ1 and variety Quest segregated as a single recessive susceptibility gene post-inoculation with Bipolaris sorokiniana, the causal agent of the disease spot blotch. Nec3 was genetically delimited to 0.14 cM representing 16.5 megabases of physical sequence containing 149 annotated high confidence genes. RNAseq and comparative analysis of the wild type and five independent nec3 mutants identified a single candidate cytochrome P450 gene (HORVU.MOREX.r2.6HG0460850) that was validated as nec3 by independent mutations that result in predicted nonfunctional proteins. Histology studies determined that nec3 mutants had an unstable cutin layer that disrupted normal Bipolaris sorokiniana germ tube development.

scholarly journals CYP76C2 , an Arabidopsis thaliana cytochrome P450 gene expressed during hypersensitive and developmental cell death

FEBS Letters ◽  
1998 ◽  
Vol 438 (3) ◽  
pp. 245-249 ◽  
Author(s):  
Laurence Godiard ◽  
Laurent Sauviac ◽  
Nathalie Dalbin ◽  
Laurence Liaubet ◽  
Didier Callard ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Cell Death ◽  
Cytochrome P450 ◽  
Cytochrome P450 Gene ◽  
P450 Gene ◽  
Developmental Cell Death

scholarly journals Mutations in a barley cytochrome P450 gene enhances pathogen induced programmed cell death and cutin layer instability

2021 ◽  
Author(s):  
G. Ameen ◽  
S. Solanki ◽  
L. Sager-Bittara ◽  
J. Richards ◽  
P. Tamang ◽  
...  
Keyword(s):  
Cell Death ◽  
Cytochrome P450 ◽  
Programmed Cell Death ◽  
Defense Mechanisms ◽  
Bipolaris Sorokiniana ◽  
Post Inoculation ◽  
Cytochrome P450 Gene ◽  
P450 Gene ◽  
Lesion Mimic ◽  
Pigmented Lesions

ABSTRACTDisease lesion mimic mutants (DLMMs) are characterized by spontaneous development of necrotic spots with various phenotypes designated as necrotic (nec) mutants in barley. The nec mutants were traditionally considered to have aberrant regulation of programmed cell death (PCD) pathways, which have roles in plant immunity and development. Most barley nec3 mutants express cream to orange necrotic lesions contrasting them from typical spontaneous DLMMs that develop dark pigmented lesions indicative of serotonin/phenolics deposition. Also, barley nec3 mutants grown under sterile conditions did not exhibit necrotic phenotypes until inoculated with adapted pathogens suggesting that they are not typical DLMMs. The F2 progeny of a cross between nec3-γ1 and variety Quest segregated as a single recessive gene post inoculation with Bipolaris sorokiniana, the causal agent of the disease spot blotch. Nec3 was genetically delimited to 0.14 cM representing 16.5 megabases of physical sequence containing 149 annotated high confidence genes. RNAseq and comparative analysis of wild type and five independent nec3 mutants identified a single candidate cytochrome P450 gene (HORVU.MOREX.r2.6HG0460850) that was validated as nec3 by independent mutations that result in predicted nonfunctional proteins. Histology studies determined that nec3 mutants had an unstable cutin layer that disrupted normal Bipolaris sorokiniana germ tube development.AUTHOR SUMMARYAt the site of pathogen infection, plant defense mechanisms rely on controlled programmed cell death (PCD) to sequester biotrophic pathogens that require living cells to extract nutrient from the host. However, these defense mechanisms are hijacked by necrotrophic plant pathogens that purposefully induce PCD mechanism to feed from the dead cells facilitating further disease development. Thus, understanding PCD responses is important for resistance to both classes of pathogens. We characterized five independent disease lesion mimic mutants of barley designated necrotic 3 (nec3) that show aberrant regulation of PCD responses upon pathogen challenge. A cytochrome P450 gene was identified as Nec3 encoding a Tryptamine 5-Hydroxylase that functions as a terminal serotonin biosynthetic enzyme in the Tryptophan pathway of plants. The nec3 mutants have disrupted serotonin biosynthesis resulting in expansive PCD, necrotrophic pathogen susceptibility and cutin layer instability. The nec3 mutants lacking serotonin deposition in pathogen induced necrotic lesions show expansive PCD and disease susceptibility suggesting a role of serotonin to sequester PCD and suppress pathogen colonization. The identification of Nec3 will facilitate functional analysis to elucidate the role serotonin plays in the elicitation or suppression of PCD immunity responses to diverse pathogens and effects it has on cutin layer biosynthesis.

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