General Information:

Id: 1,863
Diseases: MERRF - [OMIM]
Homo sapiens
BTO:0001255 skin fibroblast
article
Reference: Wu SB et al.(2010) Mitochondrial DNA mutation-elicited oxidative stress, oxidative damage, and altered gene expression in cultured cells of patients with MERRF syndrome. Mol. Neurobiol. 41: 256-266 [PMID: 20411357]

Interaction Information:

Comment 80-90% of the patients with MERRF syndrome are caused by the A8344G mutation in the tRNALys gene of mitochondrial DNA (mtDNA.
Formal Description
Interaction-ID: 14092

gene/protein mutant

c.tRNALys- A8344G

affects_activity of

disease

MERRF

Comment MERRF syndrome is characterized by myoclonus, muscle weakness, cerebellar ataxia, heart conduction block, and dementi.
Formal Description
Interaction-ID: 14093

disease

MERRF

affects_activity of

phenotype

muscle weakness

Comment MERRF syndrome is characterized by myoclonus, muscle weakness, cerebellar ataxia, heart conduction block, and dementi.
Formal Description
Interaction-ID: 14094

disease

MERRF

affects_activity of

phenotype

ataxia

Comment MERRF syndrome is characterized by myoclonus, muscle weakness, cerebellar ataxia, heart conduction block, and dementi.
Formal Description
Interaction-ID: 14095

disease

MERRF

affects_activity of

phenotype

heart block

Comment MERRF syndrome is characterized by myoclonus, muscle weakness, cerebellar ataxia, heart conduction block, and dementi.
Formal Description
Interaction-ID: 14145

disease

MERRF

decreases_activity of

process

memory

Comment The tRNALys- A8344G mutation results in not only inefficient generation of adenosine triphosphate but also increased production of reactive oxygen species (ROS) in cultured cells harboring A8344G mutation of mtDNA.
Formal Description
Interaction-ID: 14157

gene/protein mutant

c.tRNALys- A8344G

decreases_quantity of

drug/chemical compound

ATP

Comment The tRNALys- A8344G mutation results in not only inefficient generation of adenosine triphosphate but also increased production of reactive oxygen species (ROS).
Formal Description
Interaction-ID: 14159

gene/protein mutant

c.tRNALys- A8344G

increases_quantity of

drug/chemical compound

Reactive oxygen species

Comment The mRNA, protein, and enzyme activity levels of manganese-superoxide dismutase were increased, but those of Cu,Zn-SOD, catalase, and glutathione peroxidase did not show significant changes.
Formal Description
Interaction-ID: 14161

gene/protein mutant

c.tRNALys- A8344G

increases_activity of

gene/protein

SOD2

Drugbank entries Show/Hide entries for SOD2
Comment The mRNA, protein, and enzyme activity levels of manganese-superoxide dismutase were increased, but those of Cu,Zn-SOD, catalase, and glutathione peroxidase did not show significant changes.
Formal Description
Interaction-ID: 14163

gene/protein mutant

c.tRNALys- A8344G

NOT affects_activity of

gene/protein

SOD1

Drugbank entries Show/Hide entries for SOD1
Comment The mRNA, protein, and enzyme activity levels of manganese-superoxide dismutase were increased, but those of Cu,Zn-SOD, catalase, and glutathione peroxidase did not show significant changes.
Formal Description
Interaction-ID: 14164

gene/protein mutant

c.tRNALys- A8344G

NOT affects_activity of

gene/protein

GPX1

Drugbank entries Show/Hide entries for GPX1
Comment The excess ROS could damage voltage-dependent anion channels (VDAC-1 and VDAC-2) and prohibitin.
Formal Description
Interaction-ID: 14166

drug/chemical compound

Reactive oxygen species

affects_quantity of

gene/protein

VDAC1

Drugbank entries Show/Hide entries for VDAC1
Comment The excess ROS could damage voltage-dependent anion channels (VDAC-1 and VDAC-2) and prohibitin.
Formal Description
Interaction-ID: 14176

drug/chemical compound

Reactive oxygen species

affects_quantity of

gene/protein

PHB

Comment The mitochondrial and cytosolic aconitase activities in the MERRF cells were largely decreased as compared with age-matched normal subjects.
Formal Description
Interaction-ID: 14177

gene/protein mutant

c.tRNALys- A8344G

decreases_activity of

gene/protein

ACO2

Drugbank entries Show/Hide entries for ACO2
Comment The mitochondrial and cytosolic aconitase activities in the MERRF cells were largely decreased as compared with age-matched normal subjects.
Formal Description
Interaction-ID: 14178

gene/protein mutant

c.tRNALys- A8344G

decreases_activity of

gene/protein

ACO1

Comment The excess ROS could damage voltage-dependent anion channels (VDAC-1 and VDAC-2) and prohibitin.
Formal Description
Interaction-ID: 14193

drug/chemical compound

Reactive oxygen species

affects_quantity of

gene/protein

VDAC2

Drugbank entries Show/Hide entries for VDAC2
Comment The mitochondrial proteins with a decreased intensity in the MERRF cybrids were mostly related to the respiratory chain, especially the subunits of Complex I.
Formal Description
Interaction-ID: 14228

gene/protein mutant

c.tRNALys- A8344G

decreases_quantity of

complex/PPI

Mitochondrial respiratory chain complex I

Comment The ATP synthase d subunit of Complex V was up-regulated as a compensatory response in the MERRF cybrids.
Formal Description
Interaction-ID: 14229

gene/protein mutant

c.tRNALys- A8344G

increases_quantity of

gene/protein

ATP5H

Comment Besides, metabolic enzymes, mitochondrial aldehyde dehydrogenase, and delta-3, delta-2-enoyl-CoA isomerase, were more than twofold up-regulated in the MERRF cybrids as compared to wild-type cybrids.
Formal Description
Interaction-ID: 14230

gene/protein mutant

c.tRNALys- A8344G

increases_quantity of

gene/protein

ALDH2

Drugbank entries Show/Hide entries for ALDH2
Comment Besides, metabolic enzymes, mitochondrial aldehyde dehydrogenase, and delta-3, delta-2-enoyl-CoA isomerase, were more than twofold up-regulated in the MERRF cybrids as compared to wild-type cybrids.
Formal Description
Interaction-ID: 14231

gene/protein mutant

c.tRNALys- A8344G

increases_quantity of

gene/protein

ECI1

Comment The mitochondrial Lon protease was significantly up-regulated in the MERRF cybrids.
Formal Description
Interaction-ID: 14232

gene/protein mutant

c.tRNALys- A8344G

increases_quantity of

gene/protein

LONP1

Comment The activity of Lon protease in the MERRF cybrids was significantly lower than that of the wild-type cybrids. The up-regulation of Lon protease MERRF cells may be a compensation for the decrease of their enzymatic activities caused by ROS damage.
Formal Description
Interaction-ID: 14233

gene/protein mutant

c.tRNALys- A8344G

increases_activity of

gene/protein

LONP1

Comment ERp19 and Erp28, the members of the protein disulfide isomerase family were increased by more than2.5-fold in the MERRF cybrids as compared to the wild-type cybrid.
Formal Description
Interaction-ID: 14234

gene/protein mutant

c.tRNALys- A8344G

increases_quantity of

gene/protein

TXNDC12

Drugbank entries Show/Hide entries for TXNDC12
Comment ERp19 and Erp28, the members of the protein disulfide isomerase family were increased by more than2.5-fold in the MERRF cybrids as compared to the wild-type cybrid.
Formal Description
Interaction-ID: 14235

gene/protein mutant

c.tRNALys- A8344G

increases_quantity of

gene/protein

ERP29

Comment The ER-associated 150-kDa oxygen-regulated protein (ORP-150),a member of heat shock protein family, was increased by more than threefolds in the MERRF cybrids as compared with the wild-type cybrids.
Formal Description
Interaction-ID: 14236

gene/protein mutant

c.tRNALys- A8344G

increases_quantity of

gene/protein

HYOU1

Comment The myosin regulatory light chain 2, cytokeratin 8, and chloride ion channel protein 1 that were also found to be altered in the MERRF cybrids.
Formal Description
Interaction-ID: 14238

gene/protein mutant

c.tRNALys- A8344G

affects_quantity of

gene/protein

MYL12B

Comment The myosin regulatory light chain 2, cytokeratin 8, and chloride ion channel protein 1 that were also found to be altered in the MERRF cybrids.
Formal Description
Interaction-ID: 14239

gene/protein mutant

c.tRNALys- A8344G

affects_quantity of

gene/protein

KRT8

Drugbank entries Show/Hide entries for KRT8
Comment The myosin regulatory light chain 2, cytokeratin 8, and chloride ion channel protein 1 that were also found to be altered in the MERRF cybrids.
Formal Description
Interaction-ID: 14240

gene/protein mutant

c.tRNALys- A8344G

affects_quantity of

gene/protein

CLIC1

Comment The several matrix metalloproteinases (MMPs), which include MMP-1, MMP-3, and MMP-9, were over-expressed skin fibroblasts from patients with MERRF syndrome.
Formal Description
Interaction-ID: 14241

disease

MERRF

increases_quantity of

gene/protein

MMP1

Drugbank entries Show/Hide entries for MMP1
Comment The several matrix metalloproteinases (MMPs), which include MMP-1, MMP-3, and MMP-9, were over-expressed skin fibroblasts from patients with MERRF syndrome.
Formal Description
Interaction-ID: 14242

disease

MERRF

increases_quantity of

gene/protein

MMP2

Drugbank entries Show/Hide entries for MMP2
Comment The several matrix metalloproteinases (MMPs), which include MMP-1, MMP-3, and MMP-9, were over-expressed skin fibroblasts from patients with MERRF syndrome.
Formal Description
Interaction-ID: 14243

disease

MERRF

increases_quantity of

gene/protein

MMP3

Drugbank entries Show/Hide entries for MMP3
Comment The up-regulation of MMP-1 was apparently induced by the increased production of ROS in affected cells because the same change could be observed by treatment of the cells with H2O2.
Formal Description
Interaction-ID: 14244

drug/chemical compound

Reactive oxygen species

increases_quantity of

gene/protein

MMP1

Drugbank entries Show/Hide entries for MMP1
Comment The up-regulation of MMP-1 was apparently induced by the increased production of ROS in affected cells because the same change could be observed by treatment of the cells with H2O2.
Formal Description
Interaction-ID: 14245

drug/chemical compound

H2O2

increases_quantity of

gene/protein

MMP1

Drugbank entries Show/Hide entries for MMP1