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Methamphetamine causes coordinate regulation of Src, Cas, Crk, and the Jun N-terminal kinase-Jun pathway.
- Source :
-
Molecular pharmacology [Mol Pharmacol] 2002 May; Vol. 61 (5), pp. 1124-31. - Publication Year :
- 2002
-
Abstract
- The clinical abuse of methamphetamine (METH) is a major concern because it can cause long-lasting neurodegenerative effects in humans. Current concepts of the molecular mechanisms underlying these complications have centered on the formation of reactive oxygen species. Herein, we provide cDNA microarray evidence that METH administration caused the induction of c-Jun and of other members involved in the pathway leading to c-Jun activation [stress-activated protein kinase/Jun N-terminal kinase (JNK3), Crk-associated substrate-Cas and c-Src] after environmental stresses or cytokine stimulation. Reverse transcription-polymerase chain reaction analysis confirmed these increases and also showed that the expression of JNK1 and JNK3 but not JNK2 was also increased in the METH-treated mice. Western blot analysis showed that METH increased the expression of c-Jun phosphorylated at serine-63 and serine-73 residues. Other upstream members of the JNK pathway, including phosphorylated JNKs, mitogen-activated protein kinase kinase 4, mitogen-activated protein kinase kinase 7, Crk II, Cas, and c-Src were also increased at the protein level. These values returned to baseline by 1 week after drug treatment. These results are discussed in terms of their support for a possible role of the activation of the JNK/Jun pathway in the pathophysiological effects of METH.
- Subjects :
- Animals
Blotting, Western
Central Nervous System Stimulants pharmacology
Cerebral Cortex drug effects
Cerebral Cortex enzymology
Cerebral Cortex metabolism
Corpus Striatum drug effects
Corpus Striatum enzymology
Corpus Striatum metabolism
Enzyme Activation drug effects
JNK Mitogen-Activated Protein Kinases
Male
Mice
Mitogen-Activated Protein Kinase 10
Oxidative Stress drug effects
Phosphorylation
Protein-Tyrosine Kinases metabolism
Reactive Oxygen Species metabolism
Reverse Transcriptase Polymerase Chain Reaction
Gene Expression Regulation drug effects
Genes, src physiology
Methamphetamine pharmacology
Mitogen-Activated Protein Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0026-895X
- Volume :
- 61
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Molecular pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 11961130
- Full Text :
- https://doi.org/10.1124/mol.61.5.1124