Table 2 Functional significance of proteins identified in PM fraction as altered by chronic morphine
Protein name | Change (dependence vs.control) | Subcellular localization | Functional category | Protein characterization - PM |
|---|---|---|---|---|
Brain acid soluble protein 1 | Down-regulated | Cell membrane; Lipid anchor | Neuronal development and regulation | Associated with the membranes of growth cones that form the tips of elongating axons, DNA-dependent, localizes in the membrane raft domain with a cholesterol-dependent manner; changes in the localization during the development of neuronal polarity [27] |
Guanine nucleotide-binding protein subunit beta-1 | Down-regulated | Cell membrane | Signaling | Gβ1 is required for neural tube closure, neural progenitor cell proliferation and neonatal development [28]; stimulated ACII, ACIV, ACVII, inhibited ACI, ACV/VI, ACVIII [29, 30] |
Creatine kinase B-type | Down-regulated | Cytoplasm | Metabolism | Energy-related (skeletal muscle, heart, brain and spermatozoa), brain development [25], aging [31]; one of major determinants in the control of oxidative stress [17] |
Alpha-internexin | Up-regulated | Cytoplasm | Neuronal development and regulation | Copurifies with intermediate filaments from rat spinal cord and optic nerve, developmental protein involved in morphogenesis of neurons [32] |
Dihydropyrimidinase-related protein 2 | Up-regulated | Cytoplasm | Neuronal development and regulation | Neuronal development and polarity [8], cone collapse and cell migration; one of major determinants in the control of oxidative stress [17] |
NAD-dependent deacetylase sirtuin-2 | Up-regulated | Cytoplasm | Cellular development and regulation | Colocalizes with microtubules; NAD-dependent deacetylase, involved in the control of mitotic exit in the cell cycle; up-regulation may protect the brain against incurred oxidative damage [33] |
Alpha-synuclein | Up-regulated | Cytoplasm | Neuronal development and regulation | Specifically expressed in neuronal cell bodies and synapses, negative regulation of neuron apoptosis, aging; role in the pathogenesis of Parkinson’s disease [34] |
Peroxiredoxin-2 | Up-regulated | Cytoplasm | Neuronal development and regulation | Involved in redox regulation of the cell, negative regulation of neuron apoptosis; the relative abundance appears to protect cellular components by removing the low levels of hydroperoxides and peroxinitrites produced as a result of normal cellular metabolism in the cytosol [35] |
Transitional endoplasmic reticulum ATPase | Up-regulated | Cytoplasm Nucleus | Cellular development and regulation | Involved in the formation of the transitional endoplasmatic reticulum, necessary for the fragmentation of Golgi stacks during mitosis and for their reassembly after mitosis [36]; interacts with neurofibromin to control the density of dendritic spines [37] |
Glutamate dehydrogenase 1, mitochondrial | Up-regulated | Mitochondrion matrix | Metabolism | Glutamate catabolic process, long-term memory, in rat brain the glutamate dehydrogenase reaction operates in the direction of ammonia production [38] |
Succinyl-CoA:3-ketoacid-coenzyme A transferase 1, mitochondrial | Up-regulated | Mitochondrion matrix | Metabolism | A mitochondrial ketone body-activating enzyme [39]; brain development, response to drug |
Aspartate aminotransferase, mitochondrial | Down-regulated | Mitochondrion matrix | Metabolism | Amino acid metabolism, metabolite exchange between mitochondria and cytosol, fatty acid transport; its activity is related with the maintenance of amino acid homeostasis and might be an indicator of mitochondrial injury [40] |
Ubiquitin carboxyl-terminal hydrolase isozyme L1 | Down-regulated | Cytoplasm Endoplasmatic reticulum membrane | Deubiquitination Neuronal development and regulation | Involved both in the processing of ubiquitin precursors and of ubiquitinated proteins; the ubiquitination/proteasome pathway involved in synaptic plasticity [41] |
Prohibitin | Up-regulated | Mitochondrion inner membrane | Cellular development and regulation | Antiproliferative activity, role in regulating mitochondrial respiration activity and aging, response to drug [42–44]; down-regulation of prohibitin renders neurons more vulnerable to injury and reactive oxygen species production, whereas up-regulation appears to be neuroprotective [45] |
Coronin-1A | Down-regulated | Cytoplasm | Cellular development and regulation | Invagination of plasma membrane, forming protrusions of plasma membrane involved in cell locomotion; coronin-1A activity is spatially and temporally regulated by phosphoinositides [46] |
Septin-11 | Up-regulated | Cytoplasm | Cellular development and regulation | Filament-forming cytoskeletal GTPase, cell division; it is involved in dendritic maturation [47] |
Myelin basic protein S | Down-regulated | Myelin membrane | Neuronal development and regulation | Myelination, negative regulation of axonogenesis; morphine exposure colud result in a decreased number of myelinated axons [48] |
60S ribosomal protein L12 | Down-regulated | Cytoplasm | Regulatory | Binds directly to 26S ribosomal RNA; it accesses the importin 11 pathway as a major route into the nucleus [49] |