Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.64 (MPP)
 1,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PC12 cells were used to examine the in vitro antioxidative and anti-inflammatory effects of oleanolic acid (OA) and ursolic acid (UA). PC12 cells were pretreated with OA or UA at 20 and 40 microM and followed by exposure of hydrogen peroxide (H(2)O(2)) or 1-methyl-4-phenylpyridinium ion (MPP(+)) to induce cell injury. Results showed that H(2)O(2)- or MPP(+)-treatment significantly decreased cell viability and increased lactate dehydrogenase (LDH) release (P < 0.05). The pretreatment from OA or UA significantly and concentration-dependently reduced subsequent H(2)O(2)- or MPP(+)-induced cell death and LDH release (P < 0.05). Either H(2)O(2)- or MPP(+)-treatment significantly increased malonyldialdehyde (MDA) formation, decreased glutathione (GSH) content, and diminished glutathione peroxidase (GPX), catalase, and superoxide dismutase (SOD) activities (P < 0.05). The pretreatment from OA or UA significantly retained GSH, and reversed H(2)O(2)- and MPP(+)-induced impairment in catalase and SOD activities (P < 0.05), and decreased MDA formation (P < 0.05). Either H(2)O(2)- or MPP(+)-treatment significantly elevated interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha levels (P < 0.05). The pretreatments from OA or UA significantly attenuated subsequent H(2)O(2)- or MPP(+)-induced release of IL-6 and TNF-alpha (P < 0.05). Based on the observed antioxidative and anti-inflammatory activities from OA and UA, these 2 compounds were potent agents against neurodegenerative disorder.
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PMID:Antioxidative and anti-inflammatory protection of oleanolic acid and ursolic acid in PC12 cells. 1880 14

Nerve growth factor differentiated PC12 cells were used to examine the antioxidative and anti-inflammatory effects of astaxanthin (AX) and canthaxanthin (CX). PC12 cells were pretreated with AX or CX at 10 or 20 muM, and followed by exposure of hydrogen peroxide (H(2)O(2)) or 1-methyl-4-phenylpyridinium ion (MPP(+)) to induce cell injury. H(2)O(2) or MPP(+) treatment significantly decreased cell viability, increased lactate dehydrogenase (LDH) release, enhanced DNA fragmentation, and lowered mitochondrial membrane potential (MMP) (P < 0.05). The pretreatments from AX or CX concentration-dependently alleviated H(2)O(2) or MPP(+)-induced cell death, LDH release, DNA fragmentation, and MMP reduction (P < 0.05). Either H(2)O(2) or MPP(+) treatment significantly increased malonyldialdehyde (MDA) and reactive oxygen species (ROS) formations, decreased glutathione content, and lowered glutathione peroxidase (GPX) and catalase activities (P < 0.05). The pretreatments from AX or CX significantly retained GPX and catalase activities, and decreased MDA and ROS formations (P < 0.05). H(2)O(2) or MPP(+) treatment significantly decreased Na(+)-K(+)-ATPase activity, elevated caspase-3 activity and levels of interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-alpha (P < 0.05); and the pretreatments from these agents significantly restored Na(+)-K(+)-ATPase activity, suppressed caspase-3 activity and release of IL-1, IL-6, and TNF-alpha (P < 0.05). Based on the observed antioxidative and anti-inflammatory protection from AX and CX, these 2 compounds were potent agents against neurodegenerative disorder.
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PMID:Antioxidative and anti-inflammatory neuroprotective effects of astaxanthin and canthaxanthin in nerve growth factor differentiated PC12 cells. 1989 74

Neural injury leads to inflammation and activation of microglia that in turn may participate in progression of neurodegeneration. The mechanisms involved in changing microglial activity from beneficial to chronic detrimental neuroinflammation are not known but reactive oxygen species (ROS) may be involved. We have addressed this question in Nrf2-knockout mice, with hypersensitivity to oxidative stress, submitted to daily inoculation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 4 weeks. Basal ganglia of these mice exhibited a more severe dopaminergic dysfunction than wild type littermates in response to MPTP. The amount of CD11b-positive/CD45-highly-stained cells, indicative of peripheral macrophage infiltration, did not increase significantly in response to MPTP. However, Nrf2-deficient mice exhibited more astrogliosis and microgliosis as determined by an increase in messenger RNA and protein levels for GFAP and F4/80, respectively. Inflammation markers characteristic of classical microglial activation, COX-2, iNOS, IL-6, and TNF-alpha were also increased and, at the same time, anti-inflammatory markers attributable to alternative microglial activation, such as FIZZ-1, YM-1, Arginase-1, and IL-4 were decreased. These results were confirmed in microglial cultures stimulated with apoptotic conditioned medium from MPP(+)-treated dopaminergic cells, further demonstrating a role of Nrf2 in tuning balance between classical and alternative microglial activation. This study demonstrates a crucial role of Nrf2 in modulation of microglial dynamics and identifies Nrf2 as molecular target to control microglial function in Parkinson's disease (PD) progression.
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PMID:Nrf2 regulates microglial dynamics and neuroinflammation in experimental Parkinson's disease. 1990 87