Axonal transport is inhibited by a protein kinase C inhibitor in cultured isolated mouse dorsal root ganglion cells

Hiruma, Hiromi; Maruyama, Hiroshi; Katakura, Takashi; Simada, Zyun'ici B; Nishida, Sanae; Hoka, Sumio; Takenaka, Toshifumi; Kawakami, Tadashi

doi:10.1016/s0006-8993(99)01249-4

Cited by 12 publications

(8 citation statements)

References 13 publications

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“…In this study, retrograde transport of NGF was shown to be unaffected by the general PKC inhibitor Ro‐31‐8220 and rottlerin, which also affects other kinases (Davies et al, 2000), but it is more specific for the δ isoform of PKC. Taken together with the results of Hiruma et al (1999), our results suggest that the role of PKC is quite different in the process of neurotrophin uptake at the nerve terminal and in the retrograde axonal transport process itself.…”

Section: Discussionsupporting

confidence: 84%

“…General inhibition of PKC by chelerythrine was shown to inhibit axonal transport of particles in cultured DRG (Hiruma et al, 1999). Because NGF activates PKC (Wooten et al, 2001), we focused on the effect of inhibition and activation of PKC on retrograde transport of neurotrophins in vivo.…”

Section: Resultsmentioning

confidence: 99%

“…We have previously shown the importance of the lipid kinases phosphatidylinositol 3‐kinase and phosphatidylinositol 4‐kinase in the retrograde transport of neurotrophins (Reynolds et al, 1999). Because chelerythrine, an inhibitor of protein kinase C (PKC), can inhibit retrograde and anterograde axonal transport of particles in cultured DRG (Hiruma et al, 1999) and NGF can activate PKC (Heasley and Johnson, 1989), we assessed whether its activation and inhibition at the nerve terminal play a role in neurotrophin retrograde transport. Our results demonstrate that neurotrophic retrograde transport is unaffected by inhibiting PKC, whereas its activation reduces retrograde transport.…”

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confidence: 99%

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Activation of protein kinase C inhibits retrograde transport of neurotrophins in mice

Ozsarac

Weible

Reynolds

et al. 2003

J of Neuroscience Research

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Retrograde axonal transport of neurotrophins from nerve terminal to cell body requires a number of key processes, including internalization of the receptor-neurotrophin complex into vesicles and formation of multivesicular bodies and their transport along the axon. Previous studies have shown that each of these processes can be regulated by kinases. In this study, we looked at the role of protein kinase C (PKC) in retrograde transport by injecting labeled neurotrophins together with relevant pharmacological agents into the eye and measuring the accumulation of radioactivity in the trigeminal and superior cervical ganglia. Inhibitors of PKC, Ro-31-8220 and rottlerin, did not affect the retrograde transport of nerve growth factor (NGF); however, phorbol ester activation of classical and novel PKCs blocked retrograde transport. The effect of phorbol esters was partially reversed by rottlerin and Ro-31-8220. Activation of PKC has been shown to be involved in the disorganization of actin filaments. In this study, we show that Ro-31-8220 reverses growth cone collapse by phorbol 12-myristate 13-acetate and suggest that one of the effects of activating PKC on retrograde transport is to disrupt the actin filaments.

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Section: Discussionsupporting

confidence: 84%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Activation of protein kinase C inhibits retrograde transport of neurotrophins in mice

Ozsarac

Weible

Reynolds

et al. 2003

J of Neuroscience Research

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“…We treated serum-starved synoviocytes with chelerythrine chloride, a potent and specific inhibitor of PKC [19;30], which can block translocation of PKC from cytosol to the membrane [10]. In addition, chelerythrine chloride reduces anterograde and retrograde axonal transport in cultured isolated mouse dorsal root ganglion cells [31]. Serum-starved FLS cells were subjected to treatment by the inhibitor at 10 μM concentration for various times.…”

Section: Inhibition Of Pkc Activity Does Not Induce Primary Cilia Elomentioning

confidence: 99%

Adenylate cyclase regulates elongation of mammalian primary cilia

Ruan

Cheng

et al. 2009

Experimental Cell Research

115

113

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The primary cilium is a non-motile microtubule-based structure that shares many similarities with the structures of flagella and motile cilia. It is well known that the length of flagella is under stringent control, but it is not known whether this is true for primary cilia. In this study, we found that the length of primary cilia in fibroblast-like synoviocytes, either in log phase culture or in quiescent state, was confined within a range. However, when lithium was added to the culture to a final concentration of 100 mM, primary cilia of synoviocytes grew beyond this range, elongating to a length that was on average approximately 3 times the length of untreated cilia. Lithium is a drug approved for treating bipolar disorder. We dissected the molecular targets of this drug, and observed that inhibition of adenylate cyclase III (ACIII) by specific inhibitors mimicked the effects of lithium on primary cilium elongation. Inhibition of GSK-3beta by four different inhibitors did not induce primary cilia elongation. ACIII was found in primary cilia of a variety of cell types, and lithium treatment of these cell types led to their cilium elongation. Further, we demonstrate that different cell types displayed distinct sensitivities to the lithium treatment. However, in all cases examined primary cilia elongated as a result of lithium treatment. In particular, two neuronal cell types, rat PC-12 adrenal medulla cells and human astrocytes, developed long primary cilia when lithium was used at or close to the therapeutic relevant concentration (1-2 mM). These results suggest that the length of primary cilia is controlled, at least in part, by the ACIII-cAMP signaling pathway.

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“…Axonal transport is responsible for supplying a variety of materials necessary for synaptic transmission. Slow axonal transport is responsible for CaMKII transport (Lund and McQuarrie, 2001) and is regulated by both CaMKII and PKC (Hiruma et al, 1999; Kanai et al, 2001). Adult‐onset hypothyroidism leads to a decrease in the slow component of axonal transport in rat sciatic nerve (Sidenius et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

Hypothyroidism impairs long‐term potentiation in sympathetic ganglia: Electrophysiologic and molecular studies

Alzoubi

Bedawi

Aleisa

et al. 2004

J of Neuroscience Research

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Electrophysiologic and molecular techniques were used to study the effect of adult-onset hypothyroidism on synaptic plasticity in the superior cervical sympathetic ganglion. Ganglia excised from adult thyroidectomized and sham-operated rats were subjected to a brief high-frequency stimulation of the preganglionic nerve to express long-term potentiation (gLTP). Western blotting was carried out to determine the protein levels of key signaling molecules that may be involved in the expression of gLTP. Input/output relationship in ganglia from hypothyroid rats indicated a normal basal synaptic transmission, whereas activity-dependent types of synaptic plasticity, posttetanic potentiation (PTP) and gLTP, were impaired. Immunoblot analysis showed that both calcium/calmodulin kinase II (CaMKII) and phosphorylated CaMKII (P-CaMKII) levels were reduced markedly in hypothyroid rat ganglia compared to those from euthyroid controls. Additionally, protein levels of nitric oxide synthase-1, heme oxygenase-2, calmodulin, protein kinase C (PKC), and calcineurin were also reduced in hypothyroid rat ganglia. The results indicate that abnormally low basal levels of signaling molecules may be responsible for hypothyroidism-induced impairment of gLTP in superior cervical ganglia. In addition, the results indicate that synaptic plasticity in sympathetic ganglia may involve a molecular sequence of events similar to that proposed for LTP in the hippocampus.

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Axonal transport is inhibited by a protein kinase C inhibitor in cultured isolated mouse dorsal root ganglion cells

Cited by 12 publications

References 13 publications

Activation of protein kinase C inhibits retrograde transport of neurotrophins in mice

Activation of protein kinase C inhibits retrograde transport of neurotrophins in mice

Adenylate cyclase regulates elongation of mammalian primary cilia

Hypothyroidism impairs long‐term potentiation in sympathetic ganglia: Electrophysiologic and molecular studies

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