Subcellular Targeting of Nitric Oxide Synthases Mediated by Their N-Terminal Motifs

Costas-Insua, Carlos; Merino-Gracia, Javier; Aicart-Ramos, Clara; Rodrı́guez-Crespo, Ignacio

doi:10.1016/bs.apcsb.2017.07.002

Cited by 5 publications

(4 citation statements)

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“…Microglia activation leads to infection, inflammation, and trauma and releases many inflammatory factors and free radicals, including superoxide anion and NO, which induce neuronal damage and apoptosis 44,45 . iNOS is produced by macrophages and glial cells in response to infection and inflammatory factors, such as TNF‐α, IL‐1β, and endotoxin, producing large amounts of NO 46,47 . High NO concentrations exert cytotoxic effects through lipid oxidation, mitochondrial damage, signaling pathway activation or inhibition, and DNA damage 48 .…”

Section: Discussionmentioning

confidence: 99%

“… 44 , 45 iNOS is produced by macrophages and glial cells in response to infection and inflammatory factors, such as TNF‐α, IL‐1β, and endotoxin, producing large amounts of NO. 46 , 47 High NO concentrations exert cytotoxic effects through lipid oxidation, mitochondrial damage, signaling pathway activation or inhibition, and DNA damage. 48 In the central nervous system, microglia and astrocytes express TNF‐α, which binds to TNF receptors on neurons, resulting in extracellular accumulation of glutamate and excitotoxicity.…”

Section: Discussionmentioning

confidence: 99%

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Jiaohong pills attenuate neuroinflammation and amyloid‐β protein‐induced cognitive deficits by modulating the mitogen‐activated protein kinase/nuclear factor kappa‐B pathway

Zhang,

Cai,

Dong

et al. 2024

Anim Models and Exp Med

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BackgroundJiaohong pills (JHP) consist of Pericarpium Zanthoxyli (PZ) and Radix Rehmanniae, two herbs that have been extensively investigated over many years due to their potential protective effects against cognitive decline and memory impairment. However, the precise mechanisms underlying the beneficial effects remain elusive. Here, research studies were conducted to investigate and validate the therapeutic effects of JHP on Alzheimer's disease.MethodsBV‐2 cell inflammation was induced by lipopolysaccharide. AD mice were administered amyloid‐β (Aβ). Behavioral experiments were used to evaluate learning and memory ability. The levels of nitric oxide (NO), tumor necrosis factor‐alpha (TNF‐α), interleukin‐1β (IL‐1β), and interleukin‐10 (IL‐10) were detected using enzyme‐linked immunosorbent assay (ELISA). The protein expressions of inducible nitric oxide synthase (iNOS) and the phosphorylation level of mitogen‐activated protein kinase (MAPK) and nuclear factor kappa‐B (NF‐κB) were detected using Western blot. Nissl staining was used to detect neuronal degeneration.ResultsThe results demonstrated that an alcoholic extract of PZ significantly decreased the levels of NO, IL‐1β, TNF‐α, and iNOS; increased the expression level of IL‐10; and significantly decreased the phosphorylation levels of MAPK and NF‐κB. These inhibitory effects were further confirmed in the AD mouse model. Meanwhile, JHP improved learning and memory function in AD mice, reduced neuronal damage, and enriched the Nissl bodies in the hippocampus. Moreover, IL‐1β and TNF‐α in the cortex were significantly downregulated after JHP administration, whereas IL‐10 showed increased expression.ConclusionsIt was found that JHP reduced neuroinflammatory response in AD mice by targeting the MAPK/NF‐κB signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Jiaohong pills attenuate neuroinflammation and amyloid‐β protein‐induced cognitive deficits by modulating the mitogen‐activated protein kinase/nuclear factor kappa‐B pathway

Zhang,

Cai,

Dong

et al. 2024

Anim Models and Exp Med

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

“…Normally, microglia are activated to cause infection, inflammation, and trauma and then release many inflammatory factors and free radicals, including superoxide anion and NO, which induce neuronal injury and apoptosis [ 36 , 37 ]. NO is an important endogenous molecule that is normally synthesized by three nitric oxide synthases (NOSs) [ 38 ]. iNOS is produced by macrophages and glial cells in response to infection and inflammatory factors such as TNF-α, IFN-γ, and endotoxin and then produces a large amount of NO [ 39 ].…”

Section: Discussionmentioning

confidence: 99%