ArticleThe Journal of biological chemistry2010
Decreased superoxide production in macrophages of long-lived p66Shc knock-out mice.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Integrated identification of key immune related genes and patterns of immune infiltration in calcified aortic valvular disease: A network based meta-analysis.Frontiers in genetics · 2022Pooled it
- Reactive Oxygen and Nitrogen Species on Monocyte and Macrophage Biology.Antioxidants (Basel, Switzerland) · 2026Review
- Protective Role of p66Shc Deletion in Physiological Renal Aging: Effects on G Protein-Coupled Receptor 124 Expression and Associated Cellular Senescence.International journal of molecular sciences · 2025Article
- The Role of p66Shc in Cancer: Molecular Mechanisms and Therapeutic Implications.Journal of cellular and molecular medicine · 2025Review
- Reactive Oxygen Species in Macrophages: Sources and Targets.Frontiers in immunology · 2021Review
- p66shc siRNA Nanoparticles Ameliorate Chondrocytic Mitochondrial Dysfunction in Osteoarthritis.International journal of nanomedicine · 2020Article
- Endothelin receptor A and p66Shc regulate spontaneous CaFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Growth signaling and longevity in mouse models.BMB reports · 2019Review
- P66Shc expression in diabetic rat retina.BMC ophthalmology · 2018Article
- p66Shc Signaling Mediates Diabetes-Related Cognitive Decline.Scientific reports · 2018Article
- Role of adaptor protein p66Shc in renal pathologies.American journal of physiology. Renal physiology · 2018Review
- Using ROS as a Second Messenger, NADPH Oxidase 2 Mediates Macrophage Senescence via Interaction with NF-Oxidative medicine and cellular longevity · 2018Article
- The redox protein p66(shc) mediates cochlear vascular dysfunction and transient noise-induced hearing loss.Scientific reports · 2016Article
- NADPH oxidases: key modulators in aging and age-related cardiovascular diseases?Clinical science (London, England : 1979) · 2016Review
- Hydrogen Sulfide and Cellular Redox Homeostasis.Oxidative medicine and cellular longevity · 2016Review
- The expression of p66shc in peripheral blood monocytes is increased in patients with coronary heart disease and correlated with endothelium-dependent vasodilatation.Heart and vessels · 2015Article
- Sulfhydration of p66Shc at cysteine59 mediates the antioxidant effect of hydrogen sulfide.Antioxidants & redox signaling · 2014Article
- Article
- PKCδ promotes high glucose induced renal tubular oxidative damage via regulating activation and translocation of p66Shc.Oxidative medicine and cellular longevity · 2014Article
- Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I.European heart journal · 2013Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
A decrease in reactive oxygen species (ROS) production has been associated with extended life span in animal models of longevity. Mice deficient in the p66Shc gene are long-lived, and their cells are both resistant to oxidative stress and produce less ROS. Our microarray analysis of p66Shc(-/-) mouse tissues showed alterations in transcripts involved in heme and superoxide production and insulin signaling. Thus, we carried out analysis of ROS production by NADPH oxidase (PHOX) in macrophages of control and p66Shc knock-out mice. p66Shc(-/-) mice had a 40% reduction in PHOX-dependent superoxide production. To confirm whether the defect in superoxide production was a direct consequence of p66Shc deficiency, p66Shc was knocked down with siRNA in the macrophage cell line RAW264, and a 30% defect in superoxide generation was observed. The pathway of PHOX-dependent superoxide generation was investigated. PHOX protein levels were not decreased in mutant macrophages; however, the rate and extent of phosphorylation of p47phox was decreased in mutants, as was membrane translocation of the complex. Consistently, phosphorylation of protein kinase Cdelta, Akt, and ERK (the kinases responsible for phosphorylation of p47phox) was decreased. Thus, p66Shc deficiency causes a defect in activation of the PHOX complex that results in decreased superoxide production. p66Shc-deficient mice have recently been observed to be resistant to atherosclerosis and to oxidant injury in kidney and brain. Because phagocyte-derived superoxide is often a component of oxidant injury and inflammation, we suggest that the decreased superoxide production by PHOX in p66Shc-deficient mice could contribute significantly to their relative protection from oxidant injury and consequent longevity.
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