Browsing by Subject "GAP-43 Protein"
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Item Open Access Axonal growth-associated proteins.(Annual review of neuroscience, 1989-01) Skene, JHItem Open Access Bone Marrow Mesenchymal Stem Cell Transplantation Increases GAP-43 Expression via ERK1/2 and PI3K/Akt Pathways in Intracerebral Hemorrhage.(Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2017-01) Cui, Jianzhong; Cui, Changmeng; Cui, Ying; Li, Ran; Sheng, Huaxin; Jiang, Xiaohua; Tian, Yanxia; Wang, Kaijie; Gao, JunlingBackground/aims
Intracerebral hemorrhage (ICH) occurs in hypertensive patients and results in high rates of mortality and disability. This study determined whether bone marrow mesenchymal stem cell (BMSC) transplantation affects axonal regeneration and examined the underlying mechanisms after the administration of PD98059 (p-ERK1/2 inhibitor) or/ and LY294002 (PI3K inhibitor). The hypothesis that was intended to be tested was that BMSC transplantation regulates the expression of growth-associated protein-43 (GAP-43) via the ERK1/2 and PI3K/Akt signaling pathways.Methods
Seventy-five male rats (250-280 g) were subjected to intracerebral blood injection and then randomly received a vehicle, BMSCs, PD98059 or LY294002 treatment. Neurological deficits were evaluated prior to injury and at 1, 3 and 7 days post-injury. The expression of GAP-43, Akt, p-Akt, ERK1/2, and p-ERK1/2 proteins was measured by western blot analysis.Results
BMSC transplantation attenuated neurological deficits 3-7 days post-ICH. The expression of GAP-43 was increased 3 days following BMSC transplantation. However, this increase was inhibited by either PD98059 or LY294002 treatment. Treatment with both PD98059 and LY294002 was more effective than was treatment with an individual compound.Conclusion
BMSC transplantation could attenuate neurological deficits and activate axonal regeneration in this rat ICH model. The protective effects might be associated with increased GAP-43 expression by activating both the ERK1/2 and PI3K/Akt signaling pathways.Item Open Access Novel inhibitory action of tunicamycin homologues suggests a role for dynamic protein fatty acylation in growth cone-mediated neurite extension.(J Cell Biol, 1994-02) Patterson, SI; Skene, JHIn neuronal growth cones, the advancing tips of elongating axons and dendrites, specific protein substrates appear to undergo cycles of posttranslational modification by covalent attachment and removal of long-chain fatty acids. We show here that ongoing fatty acylation can be inhibited selectively by long-chain homologues of the antibiotic tunicamycin, a known inhibitor of N-linked glycosylation. Tunicamycin directly inhibits transfer of palmitate to protein in a cell-free system, indicating that tunicamycin inhibition of protein palmitoylation reflects an action of the drug separate from its previously established effects on glycosylation. Tunicamycin treatment of differentiated PC12 cells or dissociated rat sensory neurons, under conditions in which protein palmitoylation is inhibited, produces a prompt cessation of neurite elongation and induces a collapse of neuronal growth cones. These growth cone responses are rapidly reversed by washout of the antibiotic, even in the absence of protein synthesis, or by addition of serum. Two additional lines of evidence suggest that the effects of tunicamycin on growth cones arise from its ability to inhibit protein long-chain acylation, rather than its previously established effects on protein glycosylation and synthesis. (a) The abilities of different tunicamycin homologues to induce growth cone collapse very systematically with the length of the fatty acyl side-chain of tunicamycin, in a manner predicted and observed for the inhibition of protein palmitoylation. Homologues with fatty acyl moieties shorter than palmitic acid (16 hydrocarbons), including potent inhibitors of glycosylation, are poor inhibitors of growth cone function. (b) The tunicamycin-induced impairment of growth cone function can be reversed by the addition of excess exogenous fatty acid, which reverses the inhibition of protein palmitoylation but has no effect on the inhibition of protein glycosylation. These results suggest an important role for dynamic protein acylation in growth cone-mediated extension of neuronal processes.Item Open Access Posttranslational membrane attachment and dynamic fatty acylation of a neuronal growth cone protein, GAP-43.(The Journal of cell biology, 1989-02) Skene, JH; Virág, IGrowth cones, the motile apparatus at the ends of elongating axons, are sites of extensive and dynamic membrane-cytoskeletal interaction and insertion of new membrane into the growing axon. One of the most abundant proteins in growth cone membranes is a protein designated GAP-43, whose synthesis increases dramatically in most neurons during periods of axon development or regeneration. We have begun to explore the role of GAP-43 in growth cone membrane functions by asking how the protein interacts with those membranes. Membrane-washing experiments indicate that mature GAP-43 is tightly bound to growth cone membranes, and partitioning of Triton X-114-solubilized GAP-43 between detergent-enriched and detergent-depleted phases indicates considerable hydrophobicity. The hydrophobic behavior of the protein is modulated by divalent cations, particularly zinc and calcium. In vivo labeling of GAP-43 in neonatal rat brain with [35S]methionine shows that GAP-43 is initially synthesized as a soluble protein that becomes attached to membranes posttranslationally. In tissue culture, both rat cerebral cortex cells and neuron-like PC12 cells actively incorporate [3H]palmitic acid into GAP-43. Isolated growth cones detached from their cell bodies also incorporate labeled fatty acid into GAP-43, suggesting active turnover of the fatty acid moieties on the mature protein. Hydrolysis of ester-like bonds with neutral hydroxylamine removes the bound fatty acid and exposes new thiol groups on GAP-43, suggesting that fatty acid is attached to the protein's only two cysteine residues, located in a short hydrophobic domain at the amino terminus. Modulation of the protein's hydrophobic behavior by divalent cations suggests that other domains, containing large numbers of negatively charged residues, might also contribute to GAP-43-membrane interactions. Our observations suggest a dynamic and reversible interaction of GAP-43 with growth cone membranes.