Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After complete cat spinal cord transection, a collagen matrix was used to bridge the gap. Vascular supply was increased to the transection site with an omental pedicle. Before hardening, either 4-aminopyridine, laminin, glia maturation factor, or lipid angiogenic factor were mixed into the collagen. Surgically reconstructed animals were compared to transection-only controls and observed for 90 days. Fluoro-Gold was injected distal to the transection site on day 75. Immunocytochemical examination of brain and spinal cord tissue was done on day 90. Examination revealed supraspinal catecholaminergic fibers present in the collagen bridge and distal cord tissue only in cats with surgical reconstruction. Fluoro-Gold particles were found localized in locus coeruleus and other noradrenergic pontine neurons. Distal to the transection, double immunostaining with synaptophysin and tyrosine hydroxylase or dopamine-beta-hydroxylase revealed dot-like deposits closely apposed to preganglionic sympathetic neurons suggestive of synaptic connectivity to these targets. Results indicate that considerable outgrowth of specific supraspinal fibers can be induced following spinal transection and reconstruction, and that such fibers may be extending and contacting appropriate distal target tissue in the cord.
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PMID:Coerulospinal fiber regeneration in transected feline spinal cord. 785 97

In order to study the intracellular regulatory function of glia maturation factor (GMF) in neuronal cells, we achieved a 10-fold overexpression of GMF in the rat pheochromocytoma cell line PC12 by infection with a replication-defective human adenovirus carrying a rat GMF cDNA insert. These cells showed a 3.6-fold increase in the activity of p38 MAP kinase, a 3.8-fold increase in the activity of MAPKAP-K2 (MAP kinase-activated protein kinase 2), and a 4.2-fold increase in the activity of tyrosine hydroxylase (TH). We also detected an increase in the phosphorylation of TH and the 25-kDa heat shock protein (Hsp25) without a concomitant increase in their corresponding protein levels, suggesting a posttranslational modification. It was previously established that in PC12 cells, MAPKAP-K2 is an immediate target of p38, and both TH and Hsp25 are immediate targets of MAPKAP-K2. The current in vivo results are in concordance with our earlier in vitro finding that GMF promotes the activity of p38, and they implicate the participation of GMF in stress-induced catecholamine synthesis.
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PMID:Overexpression of glia maturation factor (GMF) in PC12 pheochromocytoma cells activates p38 MAP kinase, MAPKAP kinase-2, and tyrosine hydroxylase. 975 20

The molecular mechanism mediating degeneration of nigrostriatal dopaminergic neurons in Parkinson's disease (PD) is not yet fully understood. Previously, we have shown the contribution of glia maturation factor (GMF), a proinflammatory protein in dopaminergic neurodegeneration mediated by activation of mast cells (MCs). In this study, methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced nigrostriatal neurodegeneration and astro-glial activations were determined by western blot and immunofluorescence techniques in wild type (WT) mice, MC-deficient (MC-KO) mice and GMF-deficient (GMF-KO) mice, with or without MC reconstitution before MPTP administration. We show that GMF-KO in the MCs reduces the synergistic effects of MC and Calpain1 (calcium-activated cysteine protease enzyme)-dependent dopaminergic neuronal loss that reduces motor behavioral impairments in MPTP-treated mouse. Administration of MPTP increase in calpain-mediated proteolysis in nigral dopaminergic neurons further resulting in motor decline in mice. We found that MPTP administered WT mice exhibits oxidative stress due to significant increases in the levels of malondialdehyde, superoxide dismutase and reduction in the levels of reduced glutathione and glutathione peroxidase activity as compared with both MC-KO and GMF-KO mice. The number of TH-positive neurons in the ventral tegmental area, substantia nigra and the fibers in the striatum were significantly reduced while granulocyte macrophage colony-stimulating factor (GM-CSF), MC-Tryptase, GFAP, IBA1, Calpain1 and intracellular adhesion molecule 1 expression were significantly increased in WT mice. Similarly, tyrosine hydroxylase, dopamine transporters and vesicular monoamine transporters 2 proteins expression were significantly reduced in the SN of MPTP treated WT mice. The motor behavior as analyzed by rotarod and hang test was significantly reduced in WT mice as compared with both the MC-KO and GMF-KO mice. We conclude that GMF-dependent MC activation enhances the detrimental effect of astro-glial activation-mediated oxidative stress and neuroinflammation in the midbrain, and its inhibition may slowdown the progression of PD.
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PMID:A role for glia maturation factor dependent activation of mast cells and microglia in MPTP induced dopamine loss and behavioural deficits in mice. 3198

Traumatic brain injury (TBI) causes disability and death, accelerating the progression towards Alzheimer's disease and Parkinson's disease (PD). TBI causes serious motor and cognitive impairments, as seen in PD that arise during the period of the initial insult. However, this has been understudied relative to TBI induced neuroinflammation, motor and cognitive decline that progress towards PD. Neuronal ubiquitin-C-terminal hydrolase- L1 (UCHL1) is a thiol protease that breaks down ubiquitinated proteins and its level represents the severity of TBI. Previously, we demonstrated the molecular action of glia maturation factor (GMF); a proinflammatory protein in mediating neuroinflammation and neuronal loss. Here, we show that the weight drop method induced TBI neuropathology using behavioral tests, western blotting, and immunofluorescence techniques on sections from wild type (WT) and GMF-deficient (GMF-KO) mice. Results reveal a significant improvement in substantia nigral tyrosine hydroxylase and dopamine transporter expression with motor behavioral performance in GMF-KO mice following TBI. In addition, a significant reduction in neuroinflammation was manifested, as shown by activation of nuclear factor-kB, reduced levels of inducible nitric oxide synthase, and cyclooxygenase- 2 expressions. Likewise, neurotrophins including brain-derived neurotrophic factor and glial-derived neurotrophic factor were significantly improved in GMF-KO mice than WT 72 h post-TBI. Consistently, we found that TBI enhances GFAP and UCHL-1 expression and reduces the number of dopaminergic TH-positive neurons in WT compared to GMF-KO mice 72 h post-TBI. Interestingly, we observed a reduction of THpositive tanycytes in the median eminence of WT than GMF-KO mice. Overall, we found that absence of GMF significantly reversed these neuropathological events and improved behavioral outcome. This study provides evidence that PD-associated pathology progression can be initiated upon induction of TBI.
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PMID:Absence of Glia Maturation Factor Protects from Axonal Injury and Motor Behavioral Impairments after Traumatic Brain Injury. 3256 89