Ca2+/calmodulin-dependent protein kinase type IV in dorsal root ganglion: colocalization with peptides, axonal transport and effect of axotomy

Ji, Ru-Rong; Shi, Tie‐Jun Sten; Xu, Zhi‐Qing David; Zhang, Q.; Sakagami, Hiroyuki; Tsubochi, Hiroyoshi; Kondo, Hisatake; Hökfelt, Tomas

doi:10.1016/0006-8993(95)01316-4

Cited by 14 publications

(22 citation statements)

References 22 publications

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“…However, axotomy decreases the proportion of CaMKIV-positive DRG neurons and injury effects on CNS (Ji et al, 1996). Changes in CaMKII have been determined in other models of peripheral nerve injury.…”

Section: Discussionmentioning

confidence: 99%

Depression of Ca²⁺/calmodulin‐dependent protein kinase II in dorsal root ganglion neurons after spinal nerve ligation

Kojundžić

Puljak

Hogan

et al. 2009

J of Comparative Neurology

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The enzyme calcium/calmodulin-dependent protein kinase II (CaMKII) is associated with memory and its α isoform is critical for development of activity-induced synaptic changes. Therefore, we hypothesized that CaMKII is involved in altered function of dorsal root ganglion (DRG) neurons after neuronal injury. To test this hypothesis, Sprague–Dawley rats were made hyperalgesic by L5 and L6 spinal nerve ligation (SNL), and changes in total phosphorylated and unphosphorylated CaMKII (tCaMKII) and phosphorylated form of its α isoform (pCaMKIIα) were analyzed using immunochemistry in different subpopulations of DRG. SNL did not induce any changes in tCaMKII between experimental groups, while the overall percentage of pCaMKIIα-positive neurons in injured L5 DRG SNL (24.8%) decreased significantly when compared to control (41.7%). SNL did not change the percentage of pCaMKIIα/N52 colabeled neurons but decreased the percentage of N52-negative nonmyelinated neurons that expressed pCaMKIIα from 27% in control animals to 11% after axotomy. We also observed a significant decrease in the percentage of small nonpeptidergic neurons labeled with IB4 (37.6% in control vs. 4.0% in L5 SNL DRG), as well as a decrease in the percentage of pCaMKIIα/IB4 colabeled neurons in injured L5 DRGs (27% in control vs. 1% in L5 DRG of SNL group). Our results show that reduction in pCaMKIIα levels following peripheral injury is due to the loss of IB4-positive neurons. These results indicate that diminished afferent activity after axotomy may lead to decreased phosphorylation of CaMKIIα.

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Section: Discussionmentioning

confidence: 99%

Depression of Ca²⁺/calmodulin‐dependent protein kinase II in dorsal root ganglion neurons after spinal nerve ligation

Kojundžić

Puljak

Hogan

et al. 2009

J of Comparative Neurology

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“…One CaM kinase, CaM kinase IV, is localized in many DRG neurons (Sakagami et al, 1994) and is implicated in regulating gene expression (Sun et al, 1996). Previous studies on CaM kinase IV in embryonic and adult DRG indicated that it is detectable in rat DRG as early as E15 and is expressed preferentially in small neurons in sensory ganglion (Sakagami et al, 1994;Ji et al, 1996). However, CaM kinase IV expression is not well correlated with CGRP in adult DRG neurons and was not confined to CGRP-IR neurons in our RS-containing cultures (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Depolarization Stimulates Initial Calcitonin Gene-Related Peptide Expression by Embryonic Sensory NeuronsIn Vitro

MacPhedran

Hall

1998

J. Neurosci.

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The neuropeptide calcitonin gene-related peptide (CGRP) is expressed by one-third of adult rat lumbar dorsal root ganglion (DRG) neurons, many of which mediate pain sensation or cause vasodilation. The factors that regulate the developmental expression of CGRP are poorly understood. Embryonic DRG neurons initially lack CGRP. When these neurons were stimulated in culture by serum or persistent 50 mM KCl application, the same percentage of CGRP-immunoreactive (CGRP-IR) neurons developed in vitro as was seen in the adult DRG in vivo. The addition of the L-type calcium channel blockers, 5 M nifedipine or 10 M verapamil, dramatically decreased the proportion of CGRP-IR neurons that developed, although the N-type calcium channel blocker, 2.5 M -conotoxin, was less effective. By contrast, the sodium channel blocker 1 M tetrodotoxin had no effect on CGRP expression after depolarization. Fura-2 ratiometric imaging demonstrated that mean intracellular free calcium levels increased from 70 to 135 nM with chronic depolarization, and the addition of nifedipine inhibited that increase. Only a subpopulation of neurons had elevated calcium concentrations during chronic depolarization, and they were correlated with CGRP expression. Key signal transduction pathways were tested pharmacologically for their role in CGRP expression after depolarization; the addition of the CaM kinase inhibitor KN-62 reduced the proportion of CGRP-IR neurons to basal levels. By contrast, protein kinase A and protein kinase C were not implicated in the depolarization-induced CGRP increases. These data suggest that depolarization and the subsequent Ca 2ϩ -based signal transduction mechanisms play important roles in the de novo expression of CGRP by specific embryonic DRG neurons.

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“…CaMK IV expression is mainly restricted to the brain (28,29), thymus, and testes (30,31). CaMK IV is localized to the nucleus in neurons (32,33). It has been implicated in Ca 2ϩ -dependent transcription regulation through activation of the cAMP response-element binding protein (CREB) (34), activating transcription factor-1 (ATF1) (35), activation protein-1 (AP-1) (36), and serum-response factor (SRF) (37).…”

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confidence: 99%

Calcium/Calmodulin-dependent Protein Kinase IV Is Cleaved by Caspase-3 and Calpain in SH-SY5Y Human Neuroblastoma Cells Undergoing Apoptosis

McGinnis¹,

Whitton²,

Gnegy³

et al. 1998

Journal of Biological Chemistry

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We have previously demonstrated cleavage of ␣-spectrin by caspase-3 and calpain during apoptosis in SH-SY5Y neuroblastoma cells (Nath, R., Raser, K. J., Stafford, D., Hajimohammadreza, I., Posner, A., Allen, H., Talanian, R. V., Yuen, P., Gilbertsen, R. B., and Wang, K. K. (1996) Biochem. J. 319, 683-690). We demonstrate here that calcium/calmodulin-dependent protein kinase IV (CaMK IV) is cleaved during apoptosis by caspase-3 and calpain. We challenged SH-SY5Y cells with the proapoptotic agent thapsigargin. Western blot analysis revealed major CaMK IV breakdown products of 40, 38, and 33 kDa. Digestion of control SH-SY5Y lysate with purified caspase-3 produced a 38-kDa CaMK IV fragment; digestion with purified calpain produced a major fragment of 40 kDa. Pretreatment with carbobenzoxyAsp-CH 2 OC(O)-2,6-dichlorobenzene or Z-Val-Ala-Aspfluoromethylketone was able to block the caspase-3-mediated production of the 38-kDa fragment both in situ and in vitro. Calpain inhibitor II similarly blocked formation of the calpain-mediated 40-kDa fragment both in situ and in vitro. Digestion of recombinant CaMK IV by other caspase family members revealed that only caspase-3 produces a fragmentation pattern consistent to that seen in situ. The major caspase-3 and calpain cleavage sites are respectively identified as PAPD 176 *A and CG 201 *A, both within the CaMK IV catalytic domain. Furthermore, calmodulin-stimulated protein kinase activity decreases within 6 h in thapsigargin-treated SH-SY5Y. The loss of activity precedes cell death.

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Ca2+/calmodulin-dependent protein kinase type IV in dorsal root ganglion: colocalization with peptides, axonal transport and effect of axotomy

Cited by 14 publications

References 22 publications

Depression of Ca²⁺/calmodulin‐dependent protein kinase II in dorsal root ganglion neurons after spinal nerve ligation

Depression of Ca²⁺/calmodulin‐dependent protein kinase II in dorsal root ganglion neurons after spinal nerve ligation

Depolarization Stimulates Initial Calcitonin Gene-Related Peptide Expression by Embryonic Sensory NeuronsIn Vitro

Calcium/Calmodulin-dependent Protein Kinase IV Is Cleaved by Caspase-3 and Calpain in SH-SY5Y Human Neuroblastoma Cells Undergoing Apoptosis

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Ca2+/calmodulin-dependent protein kinase type IV in dorsal root ganglion: colocalization with peptides, axonal transport and effect of axotomy

Cited by 14 publications

References 22 publications

Depression of Ca2+/calmodulin‐dependent protein kinase II in dorsal root ganglion neurons after spinal nerve ligation

Depression of Ca2+/calmodulin‐dependent protein kinase II in dorsal root ganglion neurons after spinal nerve ligation

Depolarization Stimulates Initial Calcitonin Gene-Related Peptide Expression by Embryonic Sensory NeuronsIn Vitro

Calcium/Calmodulin-dependent Protein Kinase IV Is Cleaved by Caspase-3 and Calpain in SH-SY5Y Human Neuroblastoma Cells Undergoing Apoptosis

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Depression of Ca²⁺/calmodulin‐dependent protein kinase II in dorsal root ganglion neurons after spinal nerve ligation

Depression of Ca²⁺/calmodulin‐dependent protein kinase II in dorsal root ganglion neurons after spinal nerve ligation