Ubiquitin is associated with aggregates of arginine modified proteins in injured nerves

Jack, Daniel L.; Chakraborty, Goutam; Ingoglia, Nicholas A.

doi:10.1097/00001756-199201000-00012

Cited by 20 publications

(8 citation statements)

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“…Post-translation conjugation of arginine to proteins, a modification that is essential for their degradation by the ubiquitin pathway, has been shown (32,33). Crush injury to rat sciatic nerves results in a 10-fold increase in the posttranslation arginylation of proteins (34). The reduced levels of many protein bands observed in L-arg-administered mice may suggest the degradation of proteins to maintain host homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Treatment With L-Arginine Rescues Mice From Heat Stroke-Induced Death: Physiological and Molecular Mechanisms

Chatterjee

Premachandran

Sharma

et al. 2005

Shock

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Heat stroke-induced death is a major killer worldwide. Mice were subjected to acute heat stress by exposing them to whole-body hyperthermia (WBH) treatment and were used as a model to study heat stroke. Administration of L-arginine (L-arg, 120 mg/kg, i.p) 2 h after the cessation of WBH rescued the mice from heat-induced death and reduced the hypothermia. Heat shock protein 70 levels in the liver were increased significantly in heat-stressed mice administered L-arg compared with the heat-stressed group. WBH induced apoptosis, as indicated by DNA fragmentation, and increased levels of p53 and caspase-3 activity, which were significantly reduced by the administration of L-arg. The levels of inducible nitric oxide synthase in the liver, nitrite, and inflammatory cytokines like interleukin 1beta and tumor necrosis factor-alpha in the serum increased in WBH-treated mice. The levels of the above markers of heat stress significantly decreased in L-arg-treated mice. Kinin-B1 receptor (kinin-B1R) in cardiac tissue that is upregulated in heat stressed mice was significantly lower in L-arg-administered mice. These data suggest the potential use of L-arg, a nonessential amino acid that is used as an enteral diet supplement, to treat heat stroke-related injury when administered at the appropriate dose and time.

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Section: Discussionmentioning

confidence: 99%

Therapeutic Treatment With L-Arginine Rescues Mice From Heat Stroke-Induced Death: Physiological and Molecular Mechanisms

Chatterjee

Premachandran

Sharma

et al. 2005

Shock

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“…Recently, coordinated increases in mRNA levels for ubiquitin and proteasome subunits and in ubiquitin conjugation have been demonstrated in muscle under several stressful conditions in which general protein degradation rises (45). Furthermore, Jack et al (47) have shown that the ubiquitination of proteins dramatically increases within axons of rat sciatic nerve after crush injury. It has also recently been proposed that injury and memory are parts of the same continuum of responses by an organism to environmental stimuli (48).…”

Section: Discussionmentioning

confidence: 99%

Regulatory subunits of cAMP-dependent protein kinases are degraded after conjugation to ubiquitin: a molecular mechanism underlying long-term synaptic plasticity.

Hegde

Goldberg²,

Schwartz³

1993

Proc. Natl. Acad. Sci. U.S.A.

193

137

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In Aplysia, behavioral sensitization of defensive reflexes and the underlying presynaptic facilitation of sensory-to-motor neuron synapses lasts for several minutes (short term) or days to weeks (long term). Short-term sensitization has been explained by modulation ofion-channel function through cAMP-dependent protein phosphorylation. Long-term facilitation requires additional molecular changes including protein synthesis. A key event is the persistent activation of the cAMP-dependent protein kinase at baseline concentrations of cAMP. This activation is due to selective loss of regulatory (R) subunits ofPKA without any change in catalytic (C) subunits. To understand the molecular mechanisms that produce the loss of R subunits in long-term facilitation, we investigated how R subunits are degraded in extracts of Aplysia nervous tissue and in rabbit reticulocyte lysates. Degradation ofAplysia R subunits requires ATP, ubiquitin, and a particulate component that appears to be the proteasome complex. Degradation is blocked by hemin, which causes the accumulation of high molecular weight derivatives of R subunits that are likely to be ubiquitin conJugates of R subunits and intermediates in the degradative pathway. We also show that vertebrate RI and RI, subunits can be degraded through the ubiquitin pathway. We suggest that degradation is initiated by cAMP, which causes the holoenzyme to dissociate and, further, that the altered R-to-C ratio inAplysia sensory neurons is maintained in long-term facilitation by newly synthesized proteins that help target R subunits for accelerated degradation.In sensory-to-motor neuron synapses in Aplysia, cAMPdependent protein kinase (PKA) plays an important role in the presynaptic facilitation that underlies both short-term (1, 2) and long-term (3, 4) sensitization of defensive reflexes. In short-term facilitation, PKA modulates the function of ion channels directly (2,5). Several additional changes are needed to produce long-term facilitation, however, including protein synthesis (6,7). A key molecular event is the persistent activation of PKA in sensory neurons at basal concentrations of cAMP. Greenberg et al. (8) and Bergold et al. (9) showed that the amounts of regulatory (R) subunits of PKA are diminished in trained animals or after treatments that produce long-term facilitation in isolated ganglia. Since the amount of catalytic (C) subunits is not altered under these conditions, the loss of R subunits should lead to enhanced protein phosphorylation for prolonged periods (8,9). Earlier studies suggested that loss of R subunits results from accelerated proteolysis rather than from reduced synthesis (8-10). We therefore examined how R protein is degraded in Aplysia neurons.

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“…Although initially it was thought that tRNA contributed only to protein synthesis, later it was established that tRNA also worked as an amino acid donor that posttranslationally argynilates proteins at the N-terminus for ubiquitin-mediated proteolytic degradation (Chakraborty and Ingoglia, 1993; Ferber and Ciechanover, 1987; Jack et al, 1992). In regenerating sciatic nerves, an increase in N-terminal argynilated and ubiquitinated proteins was observed (Jack et al, 1992). Conversely, in the optic nerve (poor regenerative ability), N-argynilation did not occur until several days after the injury (Shyne-Athwal et al, 1988; Shyne-Athwal et al, 1986; Zanakis et al, 1984).…”

Section: The Role Of Protein Degradation In Regenerating Axonsmentioning

confidence: 99%

The role of local protein synthesis and degradation in axon regeneration

Gumy

Tan

Fawcett

2010

Experimental Neurology

111

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In axotomised regenerating axons, the first step toward successful regeneration is the formation of a growth cone. This requires a variety of dynamic morphological and biochemical changes in the axon, including the appearance of many new cytoskeletal, cell surface and signalling molecules. These changes suggest the activation of coordinated complex cellular processes. A recent development has been the demonstration that the regenerative ability of some axons depends on their capacity to locally synthesise new proteins and degrade others at the injury site autonomously from the cell body. There are also events involving the degradation of cytoskeletal and other molecules, and activation of signalling pathways, with axotomy-induced calcium changes probably being an initiating event. A future challenge will be to understand how this complex network of processes interacts in order to find therapeutic ways of promoting the regeneration of CNS axons.

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Ubiquitin is associated with aggregates of arginine modified proteins in injured nerves

Cited by 20 publications

References 0 publications

Therapeutic Treatment With L-Arginine Rescues Mice From Heat Stroke-Induced Death: Physiological and Molecular Mechanisms

Therapeutic Treatment With L-Arginine Rescues Mice From Heat Stroke-Induced Death: Physiological and Molecular Mechanisms

Regulatory subunits of cAMP-dependent protein kinases are degraded after conjugation to ubiquitin: a molecular mechanism underlying long-term synaptic plasticity.

The role of local protein synthesis and degradation in axon regeneration

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