)| PMID |
15964487 ( ) |
|---|---|
| Title | Involvement of mitochondrial potential and calcium buffering capacity in minocycline cytoprotective actions. |
| Abstract | Minocycline, a semisynthetic derivative of tetracycline, displays beneficial activity in neuroprotective in models including, Parkinson disease, spinal cord injury, amyotrophic lateral sclerosis, Huntington disease and stroke. The mechanisms by which minocycline inhibits apoptosis remain poorly understood. In the present report we have investigated the effects of minocycline on mitochondria, due to their crucial role in apoptotic pathways. In mitochondria isolated suspensions, minocycline failed to block superoxide-induced swelling but was effective in blocking mitochondrial swelling induced by calcium. This latter effect might be mediated through dissipation of mitochondrial transmembrane potential and blockade of mitochondrial calcium uptake. Consistently, minocycline fails to protect SH-SY5Y cell cultures against reactive oxygen species-mediated cell death, including malonate and 6-hydroxydopamine treatments, but it is effective against staurosporine-induced cytotoxicity. The effects of this antibiotic on mitochondrial respiratory chain complex were also analyzed. Minocycline did not modify complex IV activity, and only at the higher concentration tested (100 microM) inhibited complex II/III activity. Other members of the minocycline antibiotic family like tetracycline failed to induce these mitochondrial effects. Castilla-La Mancha, Avenida Almansa, s/n, 02006 Albacete, Spain. |
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 |
|---|---|---|---|---|
| 19986 | CYCS | cytochrome c, somatic | 3 | cytochrome c | |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | 3 | iNOS | nitric oxide synthase | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 3 | SOD1 | superoxide dismutase | |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | 1 | caspase 1 | |
| 399 | ALB | albumin | 1 | serum albumin | |
| 31395 | COX8B | cytochrome c oxidase, subunit 8B pseudogene | 1 | cytochrome c oxidase | |
| 7711 | NDUFS4 | NADH dehydrogenase (ubiquinone) Fe-S protein 4, 18kDa (NADH-coenzyme Q reductase) | 1 | mitochondrial respiratory chain complex i | |
| 11936 | FASLG | Fas ligand (TNF superfamily, member 6) | 1 | fas ligand | |
| 12716 | TRPV1 | transient receptor potential cation channel, subfamily V, member 1 | 1 | vanilloid receptor subtype 1 | |
| 11920 | FAS | Fas (TNF receptor superfamily, member 6) | 1 | Fas-ligand | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 11920 | FAS | Fas (TNF receptor superfamily, member 6) | Fas-ligand | 0.3 | pathways initiated by several apoptotic stimuli including receptor activation by Fas-ligand ( Kavurma and Khachigian 2003 or glutamate ( Stout et |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.4 | its administration in mice expressing a mutant superoxide dismutase (SOD1(G37R)) SOD1 G37R at late presymptomatic stage delayed the onset of motor |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.4 | and muscle strength decline and increased the longevity of SOD1(G37R) SOD1 G37R mice ( Kriz et al. 2002 |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.2 | expression of cycloxygenase-2 caspase-1 and inducible nitric oxide synthase (iNOS) iNOS mRNA have been described ( Chen et al. 2000 |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.2 | death by other mechanisms such as inhibition of methaloproteases or iNOS expression ( Chen et al 2000 and Sadowski and Steinmeyer |
| 11936 | FASLG | Fas ligand (TNF superfamily, member 6) | fas ligand | 1.0 | in these processes mitochondria appear to be a key point of convergence of different pathways initiated by several apoptotic stimuli including receptor activation by fas ligand kavurma and khachigian 2003 or glutamate stout et al. 1998 or after exposure to neurotoxins such as veratridine jordan et al. 2002 or staurosporine tafani et al. 2002 . |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | opening of a permeability transition pore ptp leads to mitochondrial swelling and the release of intramitochondrial proteins to the cytoplasm including cytochrome c apaf 1 and caspase family members which participate in apoptosis pathways van gurp et al 2003 joza et al 2003 and galindo et al 2003 . |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | also its administration in mice expressing a mutant superoxide dismutase sod1 g37r at late presymptomatic stage delayed the onset of motor neuron degeneration and muscle strength decline and increased the longevity of sod1 g37r mice kriz et al. 2002 . |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | the exact mechanisms by which minocycline plays these neuroprotective effects remain unknown although a reduced expression of cycloxygenase 2 caspase 1 and inducible nitric oxide synthase inos mrna have been described chen et al. 2000 . |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | nitric oxide synthase | 1.0 | the exact mechanisms by which minocycline plays these neuroprotective effects remain unknown although a reduced expression of cycloxygenase 2 caspase 1 and inducible nitric oxide synthase inos mrna have been described chen et al. 2000 . |
| 399 | ALB | albumin | serum albumin | 1.0 | mitochondrial protein concentrations were quantified spectrophotometrically micro bca protein reagent kit pierce rockford il usa with bovine serum albumin used as standard. |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | the activity of complex ii_amp_#x2013;iii succinate cytochrome c reductase was determined following the method of king 1967 . |
| 31395 | COX8B | cytochrome c oxidase, subunit 8B pseudogene | cytochrome c oxidase | 1.0 | complex iv cytochrome c oxidase; e.c.1.9.3.1 activity was determined as described by wharton and tzagoloff 1967 . |
| 7711 | NDUFS4 | NADH dehydrogenase (ubiquinone) Fe-S protein 4, 18kDa (NADH-coenzyme Q reductase) | mitochondrial respiratory chain complex i | 1.0 | consistently the mitochondrial uncoupler carbonyl cyanide 4 trifluoromethoxyphenlhydrazone fccp 1_amp_#x3bc;m fccp depleted and rotenone a mitochondrial respiratory chain complex i inhibitor 10_amp_#x3bc;m rot increased the nucleotide signal fig 1 b . |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | indeed calcium induces the release of mitochondrial cytochrome c by different mechanisms selective for brain versus liver andreyev and fiskum 1999 . |
| 12716 | TRPV1 | transient receptor potential cation channel, subfamily V, member 1 | vanilloid receptor subtype 1 | 1.0 | al 2003b drugs able to depolarize mitochondria including the protonophores fccp and carbonyl cyanide m chlorophenylhydrazone provide protection against acute glutamate neurotoxicity reynolds 1999 and vanilloid receptor subtype 1 mediated death jambrina et al. 2003 . |