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Compound
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Query: EC:2.7.10.2 (
focal adhesion kinase
)
44,029
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Radiation therapy is a frequently used treatment for prostate cancer patients. Manganese (III) meso-tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP or T2E or
BMX
-010) and other similar manganese porphyrin compounds that scavenge superoxide molecules have been demonstrated to be effective radioprotectors and prevent the development of radiation-induced fibrosis (RIF). However, understanding the molecular pathway changes associated with these compounds remains limited for radioprotection. Recent RNA-sequencing data from our laboratory revealed that MnTE-2-PyP treatment activated the nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway. Therefore, we hypothesize that MnTE-2-PyP protects the prostate from RIF by activating the NRF2 signaling pathway. We identified that MnTE-2-PyP is a post-translational activator of NRF2 signaling in prostate fibroblast cells, which plays a major role in fibroblast activation and myofibroblast differentiation. The mechanism of NRF2 activation involves an increase in hydrogen peroxide and a corresponding decrease in kelch-like ECH-associated protein 1 (KEAP1) levels. Activation of NRF2 signaling leads to an increase in expression of NAD(P)H dehydrogenase [quinone] 1 (NQO1),
nicotinamide
adenine dinucleotide (NAD
+
) levels, sirtuin activity (nuclear and mitochondrial), and superoxide dismutase 2 (SOD2) expression/activity. Increase in mitochondrial sirtuin activity correlates with a decrease in SOD2 (K122) acetylation. This decrease in SOD2 K122 acetylation correlates with an increase in SOD2 activity and mitochondrial superoxide scavenging capacity. Further, in human primary prostate fibroblast cells, the NRF2 pathway plays a major role in the fibroblast to myofibroblast transformation, which is responsible for the fibrotic phenotype. In the context of radiation protection, MnTE-2-PyP fails to prevent fibroblast to myofibroblast transformation in the absence of NRF2 signaling. Collectively, our results indicate that the activation of the NRF2 signaling pathway by MnTE-2-PyP is at least a partial mechanism of radioprotection in prostate fibroblast cells.
...
PMID:Manganese porphyrin, MnTE-2-PyP, treatment protects the prostate from radiation-induced fibrosis (RIF) by activating the NRF2 signaling pathway and enhancing SOD2 and sirtuin activity. 3222 69
Purpose
: To investigate the protective effects of
nicotinamide
riboside (NR) on oxidative damage in hydrogen peroxide (H
2
O
2
)-exposed human lens epithelial cell lines (SRA01/04) and the possible mechanisms underlying its protective effects.
Materials and methods
: SRA01/04 cells were divided into three groups: the control (CON) group, model (H
2
O
2
) group and treatment (NR+H
2
O
2
) group. Superoxide dismutase (SOD), catalase (CAT) and total glutathione (GSH) levels were detected to evaluate oxidative damage induced by different concentrations of H
2
O
2
in SRA01/04 cells. After SRA01/04 cells were treated with NR and/or H
2
O
2
, cell viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Hoechst staining, cell apoptosis was analysed using flow cytometry, reactive oxygen species (ROS) were measured with the DCFH-DA probe, and mitochondria were stained with MitoTracker to measure the mitochondrial membrane potential (MMP). In addition, western blotting was performed to detect the levels of proteins associated with apoptosis and related signalling pathways.
Results
: H
2
O
2
induced oxidative damage in SRA01/04 cells by inhibiting the activity of SOD and CAT and reducing total GSH levels. Treatment of SRA01/04 cells with NR significantly increased cell viability and reduced cell apoptosis and ROS generation, whereas SOD and CAT activities and total GSH and MMP levels were improved by the NR treatment in an H
2
O
2
-exposed cell model. Furthermore, NR significantly inhibited the activation of the MAPK pathway but promoted activation of the
JAK2
/Stat3 pathway compared with the model group.
Conclusions
: NR may alleviate oxidative damage by targeting the MAPK and
JAK2
/Stat3 pathways in H
2
O
2
-treated SRA01/04 cells. NR may represent anovel drug for preventing or treating cataracts.
...
PMID:Protective Effects of Nicotinamide Riboside on H
2
O
2
-induced Oxidative Damage in Lens Epithelial Cells. 3329 91
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