Differential Regulation of 3-Beta-Hydroxysteroid Dehydrogenase and Vanilloid Receptor TRPV1 mRNA in Sensory Neurons by Capsaicin and NGF

Donnerer, Josef; Liebmann, Ingrid; Schicho, Rudolf

doi:10.1159/000081625

Cited by 28 publications

(16 citation statements)

References 41 publications

(36 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is in line with our previous finding [17] . Treatment of rats with the selective NK 1 receptor antagonist SR140333 (1 mg/kg s.c.; 3 h before capsaicin) had no influence on the capsaicin-induced reduction in TRPV1 mRNA expression ( fig.…”

Section: Resultssupporting

confidence: 94%

The NK<sub>1</sub> Receptor Antagonist SR140333 Inhibits Capsaicin-Induced ERK Phosphorylation in Sensory Neurons

Donnerer

Liebmann²

2006

Pharmacology

Self Cite

View full text Add to dashboard Cite

Primary sensory neurons respond to a vigorous excitation via the capsaicin receptor/TRPV1 cation channel by a phosphorylation of the Jak/STAT pathway as measured by phospho-STAT3, and of the Ras/Raf-MAPK pathway as measured by phospho-MAPK/ERK1/2. In the present investigation a possible involvement of NK₁ receptors in the capsaicin-induced activation of these signal transduction pathways was investigated by protein extraction and Western immunoblotting. Phospho-MAPK/ERK1/2 and phospho-STAT3 were determined in the dorsal root ganglia (DRG) and in the sciatic nerve of rats at 3 and 6 h following a systemic capsaicin treatment without or with the pretreatment of the selective NK₁ receptor antagonist SR140333 (1 mg/kg s.c.; 3 h before capsaicin). Capsaicin evoked a threefold increase in phospho-ERK in the sciatic nerve and a two- to threefold increase in the DRG at 3 h and 6 h after the treatment. SR140333 markedly attenuated the capsaicin-induced increase in phosphorylated ERK. In the sciatic nerve the difference was significant at each individual time point (3 and 6 h, p < 0.001). In the DRG the difference was significant when the data at 3 h and 6 h were combined (p < 0.05), but not when individual time points were considered. Capsaicin evoked a four- to fivefold increase in phospho-STAT3 in the sciatic nerve and a twofold increase in the DRG at 3 and 6 h after the treatment. SR140333 less markedly attenuated the capsaicin-induced increase in phosphorylated STAT3: whereas in the sciatic nerve the difference was significant when the data at 3 h and 6 h were combined (p < 0.05), no such treatment effect of SR140333 was observed in the DRG. The expression of TRPV1 mRNA, a specific marker of capsaicin-sensitive small sensory neurons, was investigated by RT-PCR 4 days after the capsaicin treatment. Treatment of rats with SR140333 had no influence on the long-term downregulation of TRPV1 mRNA by capsaicin. Based on the present results and previous findings it can be postulated that the capsaicin-induced ERK phosphorylation in sensory neurons is not a direct effect by capsaicin, but that rather substance P release from the stimulated sensory neurons with an NK₁-mediated nerve growth factor (NGF) production is involved.

show abstract

Section: Resultssupporting

confidence: 94%

The NK<sub>1</sub> Receptor Antagonist SR140333 Inhibits Capsaicin-Induced ERK Phosphorylation in Sensory Neurons

Donnerer

Liebmann²

2006

Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

“…It has been demonstrated previously that capsaicin induces a neurochemical impairment of primary sensory neurons, and that spontaneous regeneratory processes are initiated in the small sensory neuron cell bodies in the DRG and in the C-and A ␦ -fi ber axons following the capsaicin denervation [3,4] . The present results demonstrate that characteristic regulations of phospho-ERK and phospho-STAT3 can be observed in the sciatic nerve and in the DRG after the neurotoxic lesion of sensory neurons.…”

Section: Discussionmentioning

confidence: 97%

“…In adult rats a systemic treatment with a large dose of capsaicin is known to induce a neurochemical lesion of the terminal axons of sensory C and A ␦ fi bers without destroying the cell bodies of these neurons in the dorsal root ganglia (DRG) [2] . Recent investigations of marker genes for neuronal degeneration and regeneration have elucidated that a slow spontaneous regeneration of capsaicin-lesioned sensory neurons takes place, however the recovery can be markedly improved and speed up by a treatment with the neurotrophin NGF [3,4] . For a better understanding of the sensory neuronal cell response to the capsaicin lesion and to the subsequent NGF treatment, we wanted to investigate the time course of the activation of typical intracellular signal transduction pathways [5][6][7] .…”

Section: Introductionmentioning

confidence: 99%

ERK and STAT3 Phosphorylation in Sensory Neurons during Capsaicin-Induced Impairment and Nerve Growth Factor Treatment

Donnerer

Liebmann²,

Schicho³

2005

Pharmacology

Self Cite

View full text Add to dashboard Cite

Distinct signal transduction pathways have been shown to regulate injury responses and regeneration in peripheral nerves. In the present investigation, the time courses of the induction of phospho-MAPK/ERK1/2 and of phospho-STAT3 were investigated in the dorsal root ganglia (DRG) and in the sciatic nerve of rats following a systemic capsaicin treatment without or with concomitant intraplantar NGF injections. Western blots were probed with polyclonal antibodies that specifically detect phosphorylated ERK 1/2 and STAT3. Phosphorylation of ERK clearly peaked in the sciatic nerve and in the lumbar DRGs at 6 and 10 h after the capsaicin treatment. In the following 8 days phospho-ERK decreased to very low levels and was found recovered to basal values at the time point 16 days. An additional intraplantar nerve growth factor (NGF) injection at time points 20, 44 and 92 h after the capsaicin treatment, and collection of tissues 4 h later, markedly increased the level of phospho-ERK in the sciatic nerve as well as in the DRG, as compared to the samples taken from rats at the same time points with a capsaicin treatment only. Posphorylated STAT3, which was almost non-detectable in the control sciatic nerve, clearly peaked at 6 h after the capsaicin treatment and decreased again during the following days to almost undetectable levels. The intraplantar NGF injections slightly stimulated phosho-STAT3 in the sciatic nerve. A basal level of phosphorylated STAT3 was present in DRGs of control animals, it remained at a high level up to 6 h after the capsaicin treatment, then markedly decreased and recovered on day 8 and day 16. NGF increased STAT3 phosphorylation in DRG on day 1 and day 2 above the level observed in samples taken from rats at the same time points with a capsaicin treatment only. The present study demonstrates that a capsaicin impairment of small diameter primary sensory neurons followed by an NGF treatment evokes a characteristic pattern of ERK and STAT3 activation indicative of neuronal degeneration and regeneration.

show abstract

“…Interestingly, in this study STAT3 was activated by serine-727, rather than the classical tyrosine-705 phosphorylation. In the in vivo rodent model of capsaicin-induced sensory neuron lesion, regeneration was markedly enhanced with the addition of NGF [35,118]. Interestingly, addition of NGF maintains P-STAT3, when it would otherwise decrease during regeneration, suggesting that NGF may improve regeneration through P-STAT3 [34].…”

Section: Role Of Stat3 In Neuroprotection By Growth Factors Hormonesmentioning

confidence: 99%

Role of Signal Transducer and Activator of Transcription 3 in Neuronal Survival and Regeneration

Dziennis

Alkayed²

2008

Reviews in the Neurosciences

138

108

View full text Add to dashboard Cite

SynopsisSignal Transducers and Activators of Transcription (STATs) comprise a family of transcription factors that mediate a wide variety of biological functions in the central and peripheral nervous systems. Injury to neural tissue induces STAT activation, and STATs are increasingly recognized for their role in neuronal survival. In this review, we discuss the role of STAT3 during neural development and following ischemic and traumatic injury in brain, spinal cord and peripheral nerves. We focus on STAT3 because of the expanding body of literature that investigates protective and regenerative effects of growth factors, hormones and cytokines that use STAT3 to mediate their effect, in part through transcriptional upregulation of neuroprotective and neurotrophic genes. Defining the endogenous molecular mechanisms that lead to neuroprotection by STAT3 after injury might identify novel therapeutic targets against acute neural tissue damage as well as chronic neurodegenerative disorders. KeywordsSTAT3; ischemia; neuroregeneration; neuroprotection; axotomy; spinal cord injury; neurodevelopment IntroductionSTATs are activated in the central nervous system (CNS) following injury in response to multiple signaling pathways (Fig. 1). The primary mechanism for STAT activation in brain and spinal cord is believed to be in response to the multiple cytokines and growth factors that are released after injury. However, STATs can also be activated by free radicals, excitatory neurotransmitters and other inflammatory mediators that are also produced in damaged neural tissue [3]. STATs comprise a family of seven transcription factors: STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b and STAT6 [119]. STATs are expressed during development in both neurons and glia. In adult brain, STATs are normally quiescent, but as summarized in Tables 1 and 2, several STAT family members, including STAT1, STAT3 and STAT5, have been shown to be activated after injury. Interestingly, however, different STATs seem to play different roles in injured tissue. For example, whereas STAT3 and STAT5 have been linked to neuroprotection by trophic factors and cytokines after ischemic brain or nerve injury, STAT1 activation has been associated with neuronal cell death. STAT3 and STAT5 promote neuronal survival by inducing neuroprotective genes, whereas STAT1 promotes neurodegeneration by inducing apoptotic and other cell death promoting genes. Finally, although several STAT Reprint address: Nabil J. Alkayed, M.D., Ph.D., Department of Anesthesiology & Peri-Operative Medicine, Oregon Health and Science University, 3181 S.W. Sam Jackson Park Rd., UHS-2, Portland, Oregon 97239-3098, USA, e-mail: E-mail: alkayedn@ohsu.edu. NIH Public Access Author ManuscriptRev Neurosci. Author manuscript; available in PMC 2009 May 13. Published in final edited form as:Rev Neurosci. 2008 ; 19(4-5): 341-361. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript family members influence neuronal survival during development and in response to trophic factors and cytok...

show abstract

Differential Regulation of 3-Beta-Hydroxysteroid Dehydrogenase and Vanilloid Receptor TRPV1 mRNA in Sensory Neurons by Capsaicin and NGF

Cited by 28 publications

References 41 publications

The NK<sub>1</sub> Receptor Antagonist SR140333 Inhibits Capsaicin-Induced ERK Phosphorylation in Sensory Neurons

The NK<sub>1</sub> Receptor Antagonist SR140333 Inhibits Capsaicin-Induced ERK Phosphorylation in Sensory Neurons

ERK and STAT3 Phosphorylation in Sensory Neurons during Capsaicin-Induced Impairment and Nerve Growth Factor Treatment

Role of Signal Transducer and Activator of Transcription 3 in Neuronal Survival and Regeneration

Contact Info

Product

Resources

About