Activation of GDNF-ERK-Runx1 signaling contributes to P2X3R gene transcription and bone cancer pain

Yuan, Zhulin; Liu, Xiaodan; Zhang, Zi-Xian; Li, Song; Tian, Yue; Xi, Ke; Cai, Jie; Yang, Xiao-Mei; Liu, Min; Xing, Guo-Gang

doi:10.1016/j.isci.2022.104936

Cited by 8 publications

(14 citation statements)

References 119 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 42 The pain did not immediately subside; however, there was a noticeable reduction in the painful sensations during the observation period. 43 , 44 This suggests that GDNF may suppress mechanic hyperalgesia in a model of delayed inflammatory pain. 43 , 44 In addition, Amaya et al have shown that inhibiting the activity of GDNF alleviates thermal hyperesthesia connected with the acute phase of inflammation, and as a result, it may be assumed that restoring the physiological concentration of GDNF constitutes a promising therapeutic approach to treating hyperalgesia induced by a chronic inflammatory condition.…”

Section: Discussionmentioning

confidence: 99%

“… 43 , 44 This suggests that GDNF may suppress mechanic hyperalgesia in a model of delayed inflammatory pain. 43 , 44 In addition, Amaya et al have shown that inhibiting the activity of GDNF alleviates thermal hyperesthesia connected with the acute phase of inflammation, and as a result, it may be assumed that restoring the physiological concentration of GDNF constitutes a promising therapeutic approach to treating hyperalgesia induced by a chronic inflammatory condition. 45 In the context of our study, the measurement of the concentration of GAP-43 has added significance, as it constitutes a marker for the newly created nerve fibers that contribute to the creation of nociceptive stimuli during IVD degeneration.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Evaluation of the concentration of growth associated protein-43 and glial cell-derived neurotrophic factor in degenerated intervertebral discs of the lumbosacral region of the spine

et al. 2023

View full text Add to dashboard Cite

mportant neurotrophic factors that are potentially involved in degenerative intervertebral disc (IVD) disease of the spine’s lumbosacral (L/S) region include glial cell-derived neurotrophic factor (GDNF) and growth associated protein 43 (GAP-43). The aim of this study was to determine and compare the concentrations of GAP-43 and GDNF in degenerated and healthy IVDs and to quantify and compare the GAP-43-positive and GDNF-positive nerve fibers. The study group consisted of 113 Caucasian patients with symptomatic lumbosacral discopathy (confirmed by a specialist surgeon), an indication for surgical treatment. The control group included 81 people who underwent postmortem examination. GAP-43 and GDNF concentrations were significantly higher in IVD samples from the study group compared with the control group, and the highest concentrations were observed in the degenerated IVDs that were graded 4 on the Pfirrmann scale. In the case of GAP-43, it was found that as the degree of IVD degeneration increased, the number of GAP-43-positive nerve fibers decreased. In the case of GDNF, the greatest number of fibers per mm2 of surface area was found in the IVD samples graded 3 on the Pfirrmann scale, and the number was found to be lower in samples graded 4 and 5. Hence, GAP-43 and GDNF are promising targets for analgesic treatment of degenerative IVD disease of the lumbosacral region of the spine.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evaluation of the concentration of growth associated protein-43 and glial cell-derived neurotrophic factor in degenerated intervertebral discs of the lumbosacral region of the spine

et al. 2023

View full text Add to dashboard Cite

show abstract

“…DRG and mitochondrial protein were homogenized in radioimmunoprecipitation assay (RIPA) buffer containing phosphatase and protease inhibitor cocktails (Sigma). The experimental protocol was performed in accordance with a previous study 19 . Antibodies against SIRT3 (ab246522; Abcam), FoxO3a (2497#; Cell Signaling Technology), PINK1 (23274‐1‐AP; Proteintech), Parkin (2132#; Cell Signaling Technology), LC3B (ab48394; Abcam), Beclin‐1 (3495#; Cell Signaling Technology), and P62 (5114#; Cell Signaling Technology) were purchased.…”

Section: Methodsmentioning

confidence: 99%

“…To further examine the firing properties of neurons, a large depolarizing current (500 ms, 2‐fold rheobase) was delivered to elicit the cell generating sufficient firing. All recordings were performed on medium‐small diameter neurons as described in previous reports 19,24 . We measured the rest membrane potential (RMP), the inter‐spike interval (ISI), the after‐hyperpolarization (AHP) 80% duration, the AP amplitude, the AHP amplitude, the threshold potential (TP), and the frequency of AP to evaluate the intrinsic electrophysiological properties of cells.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

SIRT3 alleviates painful diabetic neuropathy by mediating the FoxO3a‐PINK1‐Parkin signaling pathway to activate mitophagy

Yang,

Yu,

Jiang

et al. 2024

CNS Neurosci Ther

Self Cite

View full text Add to dashboard Cite

IntroductionPainful diabetic neuropathy (PDN) is a common complication of diabetes. Previous studies have implicated that mitochondrial dysfunction plays a role in the development of PDN, but its pathogenesis and mechanism have not been fully investigated.MethodsIn this study, we used high‐fat diet/low‐dose streptozotocin‐induced rats as a model of type 2 diabetes mellitus. Behavioral testing, whole‐cell patch‐clamp recordings of dorsal root ganglion (DRG) neurons, and complex sensory nerve conduction velocity studies were used to assess peripheral neuropathy. Mitochondrial membrane potential (MMP), ATP, tissue reactive oxygen species, and transmission electron microscopy were used to evaluate the function and morphology of mitochondria in DRG. Real‐time PCR, western blot, and immunofluorescence were performed to investigate the mechanism.ResultsWe found that damaged mitochondria were accumulated and mitophagy was inhibited in PDN rats. The expression of sirtuin 3 (SIRT3), which is an NAD+‐dependent deacetylase in mitochondria, was inhibited. Overexpression of SIRT3 in DRG neurons by intrathecally administered LV‐SIRT3 lentivirus ameliorated neurological and mitochondrial dysfunctions. This was evidenced by the reversal of allodynia and nociceptor hyperexcitability, as well as the restoration of MMP and ATP levels. Overexpression of SIRT3 restored the inhibited mitophagy by activating the FoxO3a‐PINK1‐Parkin signaling pathway. The effects of SIRT3 overexpression, including the reversal of allodynia and nociceptor hyperexcitability, the improvement of impaired mitochondria and mitophagy, and the restoration of PINK1 and Parkin expression, were counteracted when FoxO3a siRNA was intrathecally injected.ConclusionThese results showed that SIRT3 overexpression ameliorates PDN via activation of FoxO3a‐PINK1‐Parkin‐mediated mitophagy, suggesting that SIRT3 may become an encouraging therapeutic strategy for PDN.

show abstract

ALPK1 Expressed in IB4-Positive Neurons of Mice Trigeminal Ganglions Promotes MIA-Induced TMJ pain

Zhu

Chen

et al. 2023

Mol Neurobiol

View full text Add to dashboard Cite

Activation of GDNF-ERK-Runx1 signaling contributes to P2X3R gene transcription and bone cancer pain

Cited by 8 publications

References 119 publications

Evaluation of the concentration of growth associated protein-43 and glial cell-derived neurotrophic factor in degenerated intervertebral discs of the lumbosacral region of the spine

Evaluation of the concentration of growth associated protein-43 and glial cell-derived neurotrophic factor in degenerated intervertebral discs of the lumbosacral region of the spine

SIRT3 alleviates painful diabetic neuropathy by mediating the FoxO3a‐PINK1‐Parkin signaling pathway to activate mitophagy

ALPK1 Expressed in IB4-Positive Neurons of Mice Trigeminal Ganglions Promotes MIA-Induced TMJ pain

Contact Info

Product

Resources

About