ArticleThe Journal of biological chemistry2011
Ncb5or deficiency increases fatty acid catabolism and oxidative stress.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Cytochrome bFree radical biology & medicine · 2026Article
- CytochromebioRxiv : the preprint server for biology · 2025Article
- CYB5R4 sustains endothelial proliferation and ischemia-induced angiogenesis by maintaining RRM2-dependent nucleotide balance.bioRxiv : the preprint server for biology · 2025Article
- Vitamin E/Coenzyme Q-Dependent "Free Radical Reductases": Redox Regulators in Ferroptosis.Antioxidants & redox signaling · 2024Review
- Myoglobin regulates fatty acid trafficking and lipid metabolism in mammary epithelial cells.PloS one · 2022Article
- Genome-wide methylation profiles in monozygotic twins with discordance for ovarian carcinoma.Oncology letters · 2020Article
- Quinone and nitrofurantoin redox cycling by recombinant cytochrome b5 reductase.Toxicology and applied pharmacology · 2018Article
- NCB5OR Deficiency in the Cerebellum and Midbrain Leads to Dehydration and Alterations in Thirst Response, Fasted Feeding Behavior, and Voluntary Exercise in Mice.Cerebellum (London, England) · 2018Article
- Loss of NCB5OR in the cerebellum disturbs iron pathways, potentiates behavioral abnormalities, and exacerbates harmaline-induced tremor in mice.Metabolic brain disease · 2016Article
- Chronic Glutathione Depletion Confers Protection against Alcohol-induced Steatosis: Implication for Redox Activation of AMP-activated Protein Kinase Pathway.Scientific reports · 2016Article
- CytochromeNPJ aging and mechanisms of disease · 2016Article
- Article
- Group VIA phospholipase A2 mitigates palmitate-induced β-cell mitochondrial injury and apoptosis.The Journal of biological chemistry · 2014Article
- Common defects of mitochondria and iron in neurodegeneration and diabetes (MIND): a paradigm worth exploring.Biochemical pharmacology · 2014Review
- Lipotoxicity in the liver.World journal of hepatology · 2013Review
- Atherosclerosis susceptibility Loci identified in an extremely atherosclerosis-resistant mouse strain.Journal of the American Heart Association · 2013Article
- NAD(P)H cytochrome b5 oxidoreductase deficiency in Leishmania major results in impaired linoleate synthesis followed by increased oxidative stress and cell death.The Journal of biological chemistry · 2012Article
- Advancing animal models of human type 1 diabetes by engraftment of functional human tissues in immunodeficient mice.Cold Spring Harbor perspectives in medicine · 2012Review
- Beta-Cell Injury in Ncb5or-null Mice is Exacerbated by Consumption of a High-Fat Diet.European journal of lipid science and technology : EJLST · 2012Article
- Development of diabetes in lean Ncb5or-null mice is associated with manifestations of endoplasmic reticulum and oxidative stress in beta cells.Biochimica et biophysica acta · 2011Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
The endoplasmic reticulum-associated NADH cytochrome b(5) oxidoreductase (Ncb5or) is widely distributed in animal tissues. Ncb5or(-/-) mice develop diabetes at age 7 weeks and have increased susceptibility to the diabetogenic oxidant streptozotocin. Ncb5or deficiency also results in lipoatrophy and increased hepatocyte sensitivity to cytotoxic effects of saturated fatty acids. Here we investigate the mechanisms of these phenomena in prediabetic Ncb5or(-/-) mice and find that, despite increased rates of fatty acid uptake and synthesis and higher stearoyl-CoA desaturase (SCD) expression, Ncb5or(-/-) liver accumulates less triacylglycerol (TAG) than wild type (WT). Increased fatty acid catabolism and oxidative stress are evident in Ncb5or(-/-) hepatocytes and reflect increased mitochondrial content, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) expression, fatty acid oxidation rates, oxidative stress response gene expression, and oxidized glutathione content. Ncb5or(-/-) hepatocytes readily incorporate exogenous fatty acids into TAG but accumulate more free fatty acids (FFA) and have greater palmitate-induced oxidative stress responses and cell death than WT, all of which are alleviated by co-incubation with oleate via TAG channeling. A high fat diet rich in palmitate and oleate stimulates both lipogenesis and fatty acid catabolism in Ncb5or(-/-) liver, resulting in TAG levels similar to WT but increased intracellular FFA accumulation. Hepatic SCD-specific activity is lower in Ncb5or(-/-) than in WT mice, although Ncb5or(-/-) liver has a greater increase in Scd1 mRNA and protein levels. Together, these findings suggest that increased FFA accumulation and catabolism and oxidative stress are major consequences of Ncb5or deficiency in liver.
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