)| PMID |
17008387 ( ) |
|---|---|
| Title | Pyrrolidine dithiocarbamate inhibits induction of immunoproteasome and decreases survival in a rat model of amyotrophic lateral sclerosis. |
| Abstract | Pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear transcription factor kappa-B (NF-kappaB) and an antioxidant, has beneficial effects in animal models of various diseases, including arthritis, brain ischemia, spinal cord injury, Alzheimer's disease, and Duchenne muscular dystrophy. Because inflammation and oxidative damage are also hallmarks of amyotrophic lateral sclerosis (ALS), we studied the effect of oral PDTC treatment on G93A-superoxide dismutase 1 (SOD1) transgenic (TG) rat model of human ALS and observed that PDTC treatment significantly decreases the survival. PDTC treatment evoked the end stage of the disease at 121 +/- 21 days, whereas untreated TG animals reached the end stage at 141 +/- 13 days (p < 0.01). The DNA binding activity of NF-kappaB was not altered in G93A-SOD1 TG rats by PDTC treatment. The copper concentration in the spinal cord was increased after PDTC treatment both in G93A-SOD1 TG and wild-type rats, suggesting that increased copper may enhance the neurotoxicity of mutant SOD1. The amount of ubiquitinated proteins were significantly higher and proteasomal activity was decreased in the spinal cords of PDTC-treated TG rats compared with other groups, suggesting that PDTC treatment decreases proteasome function. Immunoblotting and immunocytochemistry showed that the level of immunoproteasome but not constitutive proteasome was increased in glia of G93A-SOD1 TG rats along with disease development. PDTC treatment completely blocked the induction of immunoproteasome expression without affecting constitutive proteasome. These results suggest that PDTC acts as an immunoproteasome inhibitor in mutant SOD1 rats and that immunoproteasome may help the nervous system to cope with deleterious effects of SOD1-G93A mutation. University of Kuopio, PO B 1627, FIN-70211 Kuopio, Finland. |
NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.
Targets by SciMiner Summary
| HUGO ID | Symbol | Target Name | #Occur | ActualStr |
|---|---|---|---|---|
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | 24 | GLT-1 | glt 1 | |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | 18 | nf kappa b | NF-kappaB | |
| 9545 | PSMB8 | proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional peptidase 7) | 16 | LMP7 | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 16 | superoxide dismutase 1 | SOD1 | SOD1-mediated | SOD | SOD1-containing | |
| 2524 | CTRL | chymotrypsin-like | 3 | chymotrypsin like | |
| 1693 | CD68 | CD68 molecule | 2 | CD68 | |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | 2 | Bcl-2 | bcl 2 | |
| 4235 | GFAP | glial fibrillary acidic protein | 2 | glial fibrillary acidic protein | |
| 5992 | IL1B | interleukin 1, beta | 2 | interleukin 1 beta | |
| 10417 | RPS27A | ribosomal protein S27a | 1 | ubiquitin | |
| 9546 | PSMB9 | proteasome (prosome, macropain) subunit, beta type, 9 (large multifunctional peptidase 2) | 1 | LMP2 | |
| 7762 | NEUROD1 | neurogenic differentiation 1 | 1 | beta2 | |
| 9538 | PSMB10 | proteasome (prosome, macropain) subunit, beta type, 10 | 1 | MECL-1 | |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | 1 | tumor necrosis factor alpha | |
| 399 | ALB | albumin | 1 | serum albumin | |
| 132 | ACTB | actin, beta | 1 | beta actin | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.6 | dithiocarbamate (PDTC), PDTC an inhibitor of nuclear transcription factor kappa-B NF-kappaB and an antioxidant has beneficial effects in animal models of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | effect of oral PDTC treatment on G93A-superoxide dismutase 1 (SOD1) SOD1 transgenic (TG) TG rat model of human ALS and observed |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.6 | The DNA binding activity of NF-kappaB was not altered in G93A-SOD1 TG rats by PDTC treatment |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | suggesting that increased copper may enhance the neurotoxicity of mutant SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | suggest that PDTC acts as an immunoproteasome inhibitor in mutant SOD1 rats and that immunoproteasome may help the nervous system to |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.6 | the treatment of AIDS (Reisinger Reisinger et al. 1990 kappa-B NF-kappaB that regulates the expression of several proinflammatory genes and some |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | 1986 kappaB accompany motor neuron degeneration either in ALS or SOD1 mutant mice (Migheli Migheli et al. 1997 Tortarolo et al. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | of several proinflammatory mediators is increased both in ALS and SOD1 mutant mice (Alexianu Alexianu et al. 2001 Elliott 2001 Nguyen |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | al. 2001 and numerous anti-inflammatory compounds prolong survival of TG SOD1 mutant mice (Drachman Drachman et al. 2002 Kriz et al. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | In addition animal models that express mutant SOD1 exclusively either in motor neurons (Pramatarova Pramatarova et al. 2001 |
| 9545 | PSMB8 | proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional peptidase 7) | LMP7 | 2.3 | to manufacturer's instructions and immunostained using rabbit polyclonal anti-proteasome 20S LMP7 (dilution dilution 1 1000 Abcam Cambridge UK rabbit polyclonal anti-proteasome |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.6 | NF-kappaB activation may promote the expression of the genes that mediate |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.6 | cord samples showed no differences in DNA binding activity of NF-kappaB between PDTC and untreated groups ( Fig 2 |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.6 | there was a trend toward increased DNA binding activity of NF-kappaB in G93A-SOD1 TG rats |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.6 | peripheral disease models by inhibiting the activation of transcription factor NF-kappaB serving as a strong antioxidant or by activating Akt-GSK3 beta |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-mediated | 2.2 | beta (Drachman Drachman et al. 2002 beta pathway reduced mutant SOD1-mediated motor neuron cell death in vitro (Koh Koh et al. |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | GLT-1 | 1.0 | that PDTC treatment prevented the reduction of the glutamate transporter GLT-1 a potential therapeutic target verified in numerous animal studies of |
| 7762 | NEUROD1 | neurogenic differentiation 1 | beta2 | 1.0 | on mouse ALS models (Cheroni Cheroni et al. 2005 beta1 beta2 and beta5 have close homologs LMP2 MECL-1 and LMP7 that |
| 9546 | PSMB9 | proteasome (prosome, macropain) subunit, beta type, 9 (large multifunctional peptidase 2) | LMP2 | 1.3 | et al. 2005 beta1 beta2 and beta5 have close homologs LMP2 MECL-1 and LMP7 that are selectively induced under certain conditions |
| 9538 | PSMB10 | proteasome (prosome, macropain) subunit, beta type, 10 | MECL-1 | 0.3 | al. 2005 beta1 beta2 and beta5 have close homologs LMP2 MECL-1 and LMP7 that are selectively induced under certain conditions such |
| 9545 | PSMB8 | proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional peptidase 7) | LMP7 | 2.3 | beta1 beta2 and beta5 have close homologs LMP2 MECL-1 and LMP7 that are selectively induced under certain conditions such as the |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | GLT-1 | 1.0 | in models of ALS by increasing expression of glutamate transporter GLT-1 (Rothstein Rothstein et al. 2005 beta-lactams because it significantly increases |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | GLT-1 | 1.0 | al. 2005 beta-lactams because it significantly increases the expression of GLT-1 and Cu concentration in the spinal cord We hypothesize that |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | GLT-1 | 1.0 | though beta-lactams and PDTC might both be able to modulate GLT-1 and Cu concentration only PDTC but not beta-lactams inhibits immunoproteasome |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | models could increase the accumulation of ubiquitinated proteins including ubiquitinated SOD1 which has been suggested to gain neurotoxic functions such as |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.6 | Even though inhibition of NF-kappaB has frequently been associated with tissue and cellular protection inhibition |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.6 | frequently been associated with tissue and cellular protection inhibition of NF-kappaB may also accelerate neurodegeneration because of the survivalsupporting role of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 2.2 | the survivalsupporting role of some NF-kappaB-regulated genes such as manganese SOD and Bcl-2 (Mattson Mattson and Camandola 2001 kappaB binding activity |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 1.0 | role of some NF-kappaB-regulated genes such as manganese SOD and Bcl-2 (Mattson Mattson and Camandola 2001 kappaB binding activity in the |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.6 | is possible that in a long-term disease such as ALS NF-kappaB activity even though being induced is not maintained at so |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.6 | does and thereby does not result in efficient inhibition of NF-kappaB In addition we cannot exclude the possibility that NF-kappaB binding |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.6 | of NF-kappaB In addition we cannot exclude the possibility that NF-kappaB binding to DNA is increased at time points other than |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.6 | experiments do not provide evidence for a central role of NF-kappaB in ALS |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.6 | In a previous study NF-kappaB immunoreactivity was found to be increased in astrocytes surrounding degenerating |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.6 | multipotent drug providing protection in various animal models by inhibiting NF-kappaB acting as an antioxidant and activating Akt-GSK3 beta pathway also |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | GLT-1 | 1.0 | as an antioxidant and activating Akt-GSK3 beta pathway also induces GLT-1 a potential drug target in brain diseases |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-containing | 2.7 | in non-neuronal cells and thereby accelerating the formation of toxic SOD1-containing protein aggregates |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | be important for coping with the toxic consequences of mutant SOD1 in tissues affected by ALS |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.6 | showed no statistically significant differences in DNA binding activity of NF-kappaB between PDTC and untreated groups n = 5 results shown |
| 9545 | PSMB8 | proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional peptidase 7) | LMP7 | 2.3 | The levels of immunoproteasome (LMP7) LMP7 increased along with the disease progression in the spinal cord |
| 9545 | PSMB8 | proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional peptidase 7) | LMP7 | 2.3 | In G93A-SOD1 TG rats the levels of 20S LMP7 protein in the spinal cord was increased 6-fold between 8 |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | GLT-1 | 1.0 | PDTC led to decreased immunoproteasome levels and increased GLT-1 levels in TG rats at the end stage whereas PDTC |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | GLT-1 | 1.0 | no effect on the levels of constitutive proteasome immunoproteasome or GLT-1 in WT rats |
| 9545 | PSMB8 | proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional peptidase 7) | LMP7 | 2.3 | PDTC treatment completely prevented the induction of 20S LMP7 at the end stage of G93A-SOD1 TG rats (A A |
| 9545 | PSMB8 | proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional peptidase 7) | LMP7 | 2.3 | A it is noteworthy that in WT animals 20S LMP7 was barely detectable or undetectable in the cytosolic fraction and |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | GLT-1 | 1.0 | effect on the levels of astrocyte specific glutamate transporter (GLT-1) GLT-1 |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | GLT-1 | 1.0 | the spinal cords of untreated TG rats the levels of GLT-1 were decreased whereas in PDTC-treated TG rats the levels of |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | GLT-1 | 1.0 | were decreased whereas in PDTC-treated TG rats the levels of GLT-1 were at the same levels as in WT rats p |
| 9545 | PSMB8 | proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional peptidase 7) | LMP7 | 2.3 | Fig 6 20S X and 20S LMP7 expression in lumbar spinal cord |
| 9545 | PSMB8 | proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional peptidase 7) | LMP7 | 2.3 | B 20S LMP7 an inducible beta-subunit of immunoproteasome was expressed only in the |
| 1693 | CD68 | CD68 molecule | CD68 | 0.3 | neurons (stained stained with NeuN and microglia (stained stained with CD68 |
| 9545 | PSMB8 | proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional peptidase 7) | LMP7 | 2.3 | B immunoproteasome 20S LMP7 was expressed mainly in astrocytes and microglia |
| 9545 | PSMB8 | proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional peptidase 7) | LMP7 | 2.3 | cord were used for immunohistochemistry with rabbit polyclonal anti-proteasome 20S LMP7 (dilution dilution 1 500 Abcam or rabbit polyclonal anti-proteasome 20S |
| 1693 | CD68 | CD68 molecule | CD68 | 0.3 | CA monoclonal NeuN (dilution dilution 1 500 Chemicon or monoclonal CD68 (dilution dilution 1 500 Serotec Oxford UK antibodies |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | Because SOD1 is a major contributor to the cellular Cu concentration copper |
| 9545 | PSMB8 | proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional peptidase 7) | LMP7 | 2.3 | spinal cord we used immunoblotting for 20S X and 20S LMP7 markers of constitutive and inducible proteasome respectively |
| 9545 | PSMB8 | proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional peptidase 7) | LMP7 | 2.3 | Instead the expression of immunoproteasome measured by immunoblotting for 20S LMP7 an inducible beta subunit was strongly increased in the spinal |
| 9545 | PSMB8 | proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional peptidase 7) | LMP7 | 2.3 | The amount of LMP7 protein was increased 6-fold between 8 and 16 weeks of |
| 9545 | PSMB8 | proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional peptidase 7) | LMP7 | 2.3 | PDTC treatment completely prevented the induction of 20S LMP7 at the end stage of G93A-SOD1 TG rats (1476 1476 |
| 9545 | PSMB8 | proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional peptidase 7) | LMP7 | 2.3 | It is noteworthy that in WT animals 20S LMP7 was barely detectable or undetectable in the cytosolic fraction ( |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | GLT-1 | 1.0 | PDTC also increased the levels of astrocyte-specific glutamate transporter (GLT-1) GLT-1 |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | GLT-1 | 1.0 | the spinal cords of untreated TG rats the levels of GLT-1 were decreased whereas in PDTC-treated TG rats the levels of |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | GLT-1 | 1.0 | were decreased whereas in PDTC-treated TG rats the levels of GLT-1 were at the same levels as in WT rats ( |
| 9545 | PSMB8 | proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional peptidase 7) | LMP7 | 2.3 | Double-labeling immunohistochemistry with confocal imaging showed that the immunoproteasome 20S LMP7 was expressed in astrocytes and microglia ( Fig 7B whereas |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.6 | dithiocarbamate ALS amyotrophic lateral sclerosis EMSA electrophoretic mobility shift assay NF-kappaB nuclear factor kappaB SOD superoxide dismutase WT wild type TG |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 2.2 | sclerosis EMSA electrophoretic mobility shift assay NF-kappaB nuclear factor kappaB SOD superoxide dismutase WT wild type TG transgenic GLT glutamate transporter |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase 1 | 1.0 | because inflammation and oxidative damage are also hallmarks of amyotrophic lateral sclerosis als we studied the effect of oral pdtc treatment on g93a superoxide dismutase 1 sod1 transgenic tg rat model of human als and observed that pdtc treatment significantly decreases the survival. |
| 5992 | IL1B | interleukin 1, beta | interleukin 1 beta | 1.0 | r use in the treatment of aids reisinger et al. 1990 kappa b nf kappab that regulates the expression of several proinflammatory genes and some genes related to apoptosis schreck et al. 1992 alpha and interleukin 1 beta nurmi et al. 2004a beta signaling nurmi et al. 2006 . |
| 2524 | CTRL | chymotrypsin-like | chymotrypsin like | 1.0 | proteasomal activity was measured from cytosolic fractions of the spinal cord samples as chymotrypsin like activity by cleavage of n succinyl leu leu val tyr 7 amino 4 methylcoumarin sigma . |
| 399 | ALB | albumin | serum albumin | 1.0 | proteasomal activity was measured in aliquots of 10 microg of protein in 50 microl volume of assay buffer 20 mm tris hcl ph 7.5 1 mm atp 2 mm mgcl 2 and 0.1% bovine serum albumin containing 100 microm n succinyl leu leu val tyr 7 amino 4 methylcoumarin . |
| 10417 | RPS27A | ribosomal protein S27a | ubiquitin | 1.0 | polyclonal anti proteasome 20s x dilution 1:1000; abcam rabbit polyclonal anti glt 1 dilution 1:1000; calbiochem la jolla ca monoclonal anti beta actin dilution 1:4000 sigma or rabbit polyclonal anti ubiquitin antibodies dilution 1:1000; dakocytomation denmark a/s glostrup denmark and horseradish peroxidase labeled anti mouse igg dilution 1:4000; ge healthcare or horseradish peroxidase labeled anti rabbit |
| 132 | ACTB | actin, beta | beta actin | 1.0 | easome 20s lmp7 dilution 1:1000; abcam cambridge uk rabbit polyclonal anti proteasome 20s x dilution 1:1000; abcam rabbit polyclonal anti glt 1 dilution 1:1000; calbiochem la jolla ca monoclonal anti beta actin dilution 1:4000 sigma or rabbit polyclonal anti ubiquitin antibodies dilution 1:1000; dakocytomation denmark a/s glostrup denmark and horseradish peroxidase labeled anti mouse igg dilution 1:4000; ge |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | glt 1 | 1.0 | structions and immunostained using rabbit polyclonal anti proteasome 20s lmp7 dilution 1:1000; abcam cambridge uk rabbit polyclonal anti proteasome 20s x dilution 1:1000; abcam rabbit polyclonal anti glt 1 dilution 1:1000; calbiochem la jolla ca monoclonal anti beta actin dilution 1:4000 sigma or rabbit polyclonal anti ubiquitin antibodies dilution 1:1000; dakocytomation denmark a/s glostrup denmark an |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | nf kappa b | 1.0 | the effect of pdtc was not mediated through nf kappa b inhibition. |
| 5992 | IL1B | interleukin 1, beta | interleukin 1 beta | 1.0 | ranscription factor nf kappab serving as a strong antioxidant or by activating akt gsk3 beta pathway cuzzocrea et al. 2002 kappab driven genes such as cyclooxygenase 2 tumor necrosis factor alpha and interleukin 1 beta drachman et al. 2002 beta pathway reduced mutant sod1 mediated motor neuron cell death in vitro koh et al. 2005 we found that pdtc treatment does not provide protection but instead significantly decr |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tumor necrosis factor alpha | 1.0 | y inhibiting the activation of transcription factor nf kappab serving as a strong antioxidant or by activating akt gsk3 beta pathway cuzzocrea et al. 2002 kappab driven genes such as cyclooxygenase 2 tumor necrosis factor alpha and interleukin 1 beta drachman et al. 2002 beta pathway reduced mutant sod1 mediated motor neuron cell death in vitro koh et al. 2005 we found that pdtc treatment does not provide protection but ins |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | glt 1 | 1.0 | the fact that pdtc treatment prevented the reduction of the glutamate transporter glt 1 a potential therapeutic target verified in numerous animal studies of als gurney et al. 1996 ; howland et al. 2002 and that pdtc treatment did not induce toxic side effects in the tg or wt rats the n |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | glt 1 | 1.0 | ducts in rat peripheral nerves calviello et al. 2005 beta lactams such as ceftriaxone which have been reported to be neuroprotective in models of als by increasing expression of glutamate transporter glt 1 rothstein et al. 2005 beta lactams because it significantly increases the expression of glt 1 and cu concentration in the spinal cord we hypothesize that even though beta lactams and pdtc might both |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | glt 1 | 1.0 | rothstein et al. 2005 beta lactams because it significantly increases the expression of glt 1 and cu concentration in the spinal cord we hypothesize that even though beta lactams and pdtc might both be able to modulate glt 1 and cu concentration only pdtc but not beta lactams inhibits immunop |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | glt 1 | 1.0 | and cu concentration in the spinal cord we hypothesize that even though beta lactams and pdtc might both be able to modulate glt 1 and cu concentration only pdtc but not beta lactams inhibits immunoproteasome because induction of immunoproteasome may be a rather selective characteristic for als models compared with models of isc |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | ed with tissue and cellular protection inhibition of nf kappab may also accelerate neurodegeneration because of the survivalsupporting role of some nf kappab regulated genes such as manganese sod and bcl 2 mattson and camandola 2001 kappab binding activity in the spinal cords of g93a sod1 tg rats no statistically significant differences between any of the untreated/pdtc treated tg and wt rat groups wer |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | glt 1 | 1.0 | in summary we report that pdtc a multipotent drug providing protection in various animal models by inhibiting nf kappab acting as an antioxidant and activating akt gsk3 beta pathway also induces glt 1 a potential drug target in brain diseases. |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | glt 1 | 1.0 | pdtc led to decreased immunoproteasome levels and increased glt 1 levels in tg rats at the end stage whereas pdtc had no effect on the levels of constitutive proteasome immunoproteasome or glt 1 in wt rats. |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | glt 1 | 1.0 | pdtc also had an effect on the levels of astrocyte specific glutamate transporter glt 1 . |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | glt 1 | 1.0 | a and c in the spinal cords of untreated tg rats the levels of glt 1 were decreased whereas in pdtc treated tg rats the levels of glt 1 were at the same levels as in wt rats. p _lt_ 0.05 n = 5 results shown are mean _amp_#177; s.d. |
| 4235 | GFAP | glial fibrillary acidic protein | glial fibrillary acidic protein | 1.0 | a constitutive proteasome 20s x was expressed in astrocytes stained with glial fibrillary acidic protein neurons stained with neun and microglia stained with cd68 . |
| 4235 | GFAP | glial fibrillary acidic protein | glial fibrillary acidic protein | 1.0 | immunohistochemistry with rabbit polyclonal anti proteasome 20s lmp7 dilution 1:500; abcam or rabbit polyclonal anti proteasome 20s x antibodies dilution 1:500; abcam and with cell markers monoclonal glial fibrillary acidic protein dilution 1:500; chemicon temecula ca monoclonal neun dilution 1:500; chemicon or monoclonal cd68 dilution 1:500; serotec oxford uk antibodies. |
| 2524 | CTRL | chymotrypsin-like | chymotrypsin like | 1.0 | to find out whether proteasomal activity is changed in g93a sod1 tg rats or by pdtc treatment we measured chymotrypsin like activity in the spinal cord tissues. |
| 2524 | CTRL | chymotrypsin-like | chymotrypsin like | 1.0 | chymotrypsin like activity was approximately on the same level in untreated wt group 902 _amp_#177; 85 n = 5 and untreated g93a sod1 tg group at the presymptomatic stage 1015 _amp_#177; 167 n = 5 . |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | glt 1 | 1.0 | the changes in immunoproteasome levels after pdtc treatment were not due to common reduction of astroglial functions because pdtc also increased the levels of astrocyte specific glutamate transporter glt 1 . |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | glt 1 | 1.0 | in the spinal cords of untreated tg rats the levels of glt 1 were decreased whereas in pdtc treated tg rats the levels of glt 1 were at the same levels as in wt rats fig 5 a and c . |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | abbreviations: pdtc pyrrolidine dithiocarbamate; als amyotrophic lateral sclerosis; emsa electrophoretic mobility shift assay; nf kappab nuclear factor kappab; sod superoxide dismutase; wt wild type; tg transgenic; glt glutamate transporter. |