Редактирование: NOX1 (раздел)

==Publications==

{{medline-entry
|title=Identification of the mechanisms by which age alters the mechanosensitivity of mesenchymal stromal cells on substrates of differing stiffness: Implications for osteogenesis and angiogenesis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28216301
|abstract=In order to identify the mechanisms by which skeletal maturity alters the mechanosensitivity of mesenchymal stromal cells (MSCs) and, the implications for osteogenesis and angiogenesis during bone formation, we compared the response of MSCs derived from children and skeletally-mature healthy adults cultured on soft and stiff collagen-coated polyacrylamide substrates. MSCs from children were more mechanosensitive, showing enhanced angiogenesis and osteogenesis on stiff substrates as indicated by increased endothelial tubule formation, [[PGF]] production, nuclear-translocation of YAP, ALP activity and mineralisation. To examine these mechanisms in more detail, a customised PCR array identified an age-dependent, stiffness-induced upregulation of [[NOX1]], VEGFR1, VEGFR2, [[WIF1]] and, of particular interest, JNK3 in cells from children compared to adults. When JNK3 activity was inhibited, a reduction in stiffness-induced driven osteogenesis was observed - suggesting that JNK3 might serve as a novel target for recapitulating the enhanced regenerative potential of children in adults suffering from bone degeneration. We investigated the age-associated changes in the capacity of MSCs for bone regeneration involving the mechanosensitive signalling pathways, which reduce the ability of adult cells to respond to biophysical cues in comparison to cells from children, who are still undergoing bone development. Our results offer new insights into the mechanobiology of MSCs and sheds new light on age-altered mechanosensitivity and, on why children have such an immense capacity to regenerate their skeletal system. We have identified the mechanisms by which skeletal maturity alters the mechanosensitivity of mesenchymal stromal cells and an age-dependent, stiffness-induced upregulation of a number of prominent genes including, most notably, JNK3 in children cells, thus suggesting its potential to promote enhanced bone repair.
|mesh-terms=* Active Transport, Cell Nucleus
* Adaptor Proteins, Signal Transducing
* Adult
* Aging
* Biomechanical Phenomena
* Bone Regeneration
* Cell Differentiation
* Cells, Cultured
* Child
* Humans
* MAP Kinase Signaling System
* Mechanotransduction, Cellular
* Mesenchymal Stem Cells
* Mitogen-Activated Protein Kinase 10
* Neovascularization, Physiologic
* Osteogenesis
* Phosphoproteins
* Placenta Growth Factor
* Transcription Factors
* Up-Regulation
* Vascular Endothelial Growth Factor A
* Young Adult
|keywords=* Ageing
* Children MSCs
* JNK3
* MSCs
* Mechanosensitivity
* Osteogenesis
* Stem cells
|full-text-url=https://sci-hub.do/10.1016/j.actbio.2017.02.031
}}
{{medline-entry
|title=Antioxidant Supplementation Modulates Age-Related Placental Bed Morphology and Reproductive Outcome in Mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26178715
|abstract=The number of women who delay their first childbirth is increasing. This demographic shift is an important health issue because advanced maternal age is a risk factor for reproductive capacity loss and the occurrence of placental bed disorders that may lead to placenta abruption, preeclampsia, and placenta insufficiency. A redox imbalance status, resulting from the enhanced production of reactive oxygen species or their deficient neutralization, is proposed to occur in this setting. Thus, uterine redox status was evaluated in young (8- to 12-wk-old) and reproductively aged (38- to 42-wk-old) mice. In addition, it was hypothesized that specific dietary antioxidant supplementation would restore the balance and improve the reproductive outcome of aging female mice. To test this hypothesis, two different antioxidants, the nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor apocynin and the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy (TEMPOL), were added to the drinking water of female mice prior to and during pregnancy. Compared to younger females, uteri from reproductively aged nonpregnant mice exhibited areas of endometrial cystic dilation, increased level of [[NOX1]] expression, and enhanced protein carbonylation, especially in the apical surface of the luminal epithelium. Both antioxidants decreased protein carbonylation level in the uterus of reproductively aged mice. When reproductively aged females became pregnant, the litter size was smaller and fetuses were heavier. The change was accompanied by a significant decrease in decidua thickness. Provision of apocynin significantly increased litter size and restored decidua thickness. Reproductively aged mice provided with TEMPOL did not evidence such benefits, but whereas apocynin normalized fetal birth weight, TEMPOL further increased it. These findings emphasize that uterine redox balance is important for reproductive success and suggest that age-related redox imbalance might be compensated by specific antioxidant supplementation. 
|mesh-terms=* Acetophenones
* Aging
* Animals
* Antioxidants
* Cyclic N-Oxides
* Decidua
* Female
* Fetus
* Litter Size
* Mice
* Mice, Inbred C57BL
* NADH, NADPH Oxidoreductases
* NADPH Oxidase 1
* Nitric Oxide Synthase
* Placenta
* Pregnancy
* Protein Carbonylation
* Reproduction
* Spin Labels
* Superoxide Dismutase
* Uterus
|keywords=* TEMPOL
* aging
* apocynin
* decidua
* litter size
* oxidative stress
* pregnancy
* superoxide dismutase
|full-text-url=https://sci-hub.do/10.1095/biolreprod.114.127746
}}
{{medline-entry
|title=NADPH oxidase [[NOX1]] is involved in activation of protein kinase C and premature senescence in early stage diabetic kidney.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25701431
|abstract=Increased oxidative stress and activation of protein kinase C (PKC) under hyperglycemia have been implicated in the development of diabetic nephropathy. Because reactive oxygen species derived from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, [[NOX1]] accelerate the translocation of PKC isoforms, [[NOX1]] is postulated to play a causative role in the development of diabetic nephropathy. Hyperglycemia was induced in wild-type and Nox1-deficient mice (KO) by two doses of streptozotocin injection. At 3 weeks after the induction of hyperglycemia, glomeruli and cortical tubules were isolated from kidneys. The mRNA level of Nox1 was significantly upregulated in the renal cortex at 3 weeks of hyperglycemia. Urinary albumin and expression of inflammatory or fibrotic mediators were similarly elevated in diabetic wild-type and KO; however, increases in glomerular volume and mesangial matrix area were attenuated in diabetic KO. Nox1 deficiency significantly reduced the levels of renal thiobarbituric acid-reacting substances and 8-hydroxydeoxyguanosine, membranous translocation of PKCα/β, activity of PKC, and phosphorylation of p38 mitogen-activated protein kinase in the diabetic kidney. Furthermore, increased staining of senescence-associated β-galactosidase in glomeruli and cortical tubules of diabetic mice was significantly suppressed in KO. Whereas the levels of cyclin-dependent kinase inhibitors, p16(INK4A) and p21(Cip1), were equivalent between the genotypes, increased levels of p27(Kip1) and γ-H2AX, a biomarker for DNA double-strand breaks, were significantly attenuated in isolated glomeruli and cortical tubules of diabetic KO. Taken together, [[NOX1]] modulates the p38/p27(Kip1) signaling pathway by activating PKC and promotes premature senescence in early stage diabetic nephropathy. 
|mesh-terms=* Animals
* Blotting, Western
* Cells, Cultured
* Cellular Senescence
* Diabetes Mellitus, Experimental
* Diabetic Nephropathies
* Glomerular Mesangium
* Hyperglycemia
* Immunoenzyme Techniques
* Male
* Mice
* Mice, Inbred C57BL
* Mice, Knockout
* NADH, NADPH Oxidoreductases
* NADPH Oxidase 1
* Oxidation-Reduction
* Oxidative Stress
* Protein Kinase C
* RNA, Messenger
* Reactive Oxygen Species
* Real-Time Polymerase Chain Reaction
* Reverse Transcriptase Polymerase Chain Reaction
* Signal Transduction
* beta-Galactosidase
* p38 Mitogen-Activated Protein Kinases
|keywords=* Diabetic nephropathy
* Free radicals
* NADPH oxidase
* NOX1
* Protein kinase C
* Senescence
|full-text-url=https://sci-hub.do/10.1016/j.freeradbiomed.2015.02.009
}}