Apoptosis Signal-Regulating Kinase 1 Is Involved in  Brain-Derived Neurotrophic Factor (BDNF)-Enhanced Cell Motility and Matrix Metalloproteinase 1 Expression in Human Chondrosarcoma Cells

Lin, Chih-Yang; Chang, Sunny Li‐Yun; Fong, Yi‐Chin; Hsu, Chin‐Jung; Tang, Chih-Hsin

doi:10.3390/ijms140815459

Cited by 25 publications

(21 citation statements)

References 58 publications

(58 reference statements)

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“…In our study, the expression of p-p38 and p-JNK were upregulated in the SDH of our CYP-induced cystitis model, suggesting the activation of p38/JNK signaling pathway. In addition, ASK1-dependent p38/JNK was reported as a downstream molecule of the BDNF signaling pathway [49]. BDNF-TrkB signaling regulates the progress of p38/JNK signaling.…”

Section: Discussionmentioning

confidence: 99%

BDNF promotes activation of astrocytes and microglia contributing to neuroinflammation and mechanical allodynia in cyclophosphamide-induced cystitis

Ding

Chen

et al. 2020

J Neuroinflammation

102

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Background: Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) often grieve over a low quality of life brought about by chronic pain. In our previous studies, we determined that neuroinflammation of the spinal dorsal horn (SDH) was associated with mechanisms of interstitial cystitis. Moreover, it has been shown that brain-derived neurotrophic factor (BDNF) participates in the regulation of neuroinflammation and pathological pain through BDNF-TrkB signaling; however, whether it plays a role in cyclophosphamide (CYP)-induced cystitis remains unclear. This study aimed to confirm whether BDNF-TrkB signaling modulates neuroinflammation and mechanical allodynia in CYP-induced cystitis and determine how it occurs. Methods: Systemic intraperitoneal injection of CYP was performed to establish a rat cystitis model. BDNF-TrkB signaling was modulated by intraperitoneal injection of the TrkB receptor antagonist, ANA-12, or intrathecal injection of exogenous BDNF. Mechanical allodynia in the suprapubic region was assessed using the von Frey filaments test. The expression of BDNF, TrkB, p-TrkB, Iba1, GFAP, p-p38, p-JNK, IL-1β, and TNF-α in the L6-S1 SDH was measured by Western blotting and immunofluorescence analysis. Results: BDNF-TrkB signaling was upregulated significantly in the SDH after CYP was injected. Similarly, the expressions of Iba1, GFAP, p-p38, p-JNK, IL-1β, and TNF-α in the SDH were all upregulated. Treatment with ANA-12 could attenuate mechanical allodynia, restrain activation of astrocytes and microglia and alleviate neuroinflammation. Besides, the intrathecal injection of exogenous BDNF further decreased the mechanical withdrawal threshold, promoted activation of astrocytes and microglia, and increased the release of TNF-α and IL-1β in the SDH of our CYP-induced cystitis model. Conclusions: In our CYP-induced cystitis model, BDNF promoted the activation of astrocytes and microglia to release TNF-α and IL-1β, aggravating neuroinflammation and leading to mechanical allodynia through BDNF-TrkB-p38/JNK signaling.

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Section: Discussionmentioning

confidence: 99%

BDNF promotes activation of astrocytes and microglia contributing to neuroinflammation and mechanical allodynia in cyclophosphamide-induced cystitis

Ding

Chen

et al. 2020

J Neuroinflammation

102

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“…In human cervix carcinoma cells, p38MAPK activation may be a key upstream signal of TNF-α-induced apoptosis and attenuation of the p38MAPK pathway by overexpression of DDB2 (a DNA repair protein) may be responsible for acquired TNF-α resistance (31). ASK1, a MAPKKK activated in cells treated with TNF-α, activates MKK3/MAPKK6 (or MKK6) and p38MAPK in turn, thus inducing apoptosis (32). However, another study demonstrated that ASK1 mediates anti-apoptotic signals (33).…”

Section: Discussionmentioning

confidence: 99%

p38MAPK activation mediates tumor necrosis factor-α-induced apoptosis in glioma cells

Zhang

Wang

et al. 2014

Molecular Medicine Reports

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Gliomas are a type of heterogeneous primary central nervous system tumor, which arise from the glial cells; these types of tumor generally respond poorly to surgery, radiation and conventional chemotherapy. Tumor necrosis factor‑α (TNF‑α) has been suggested to produce an antitumor effect by binding to specific receptors on the tumor cell membrane to induce apoptosis. TNF‑α is known to activate a number of signaling pathways, including extracellular signal‑regulated protein kinase, c‑Jun N‑terminal kinase (JNK), p38 mitogen‑activated protein kinase (p38MAPK), nuclear factor‑κB and caspase cascades, depending on the cell type. However, the involvement of p38MAPK signaling in TNF‑α‑induced apoptosis in glioma cells remains unclear. In the current study, the role of p38MAPK in TNF‑α‑induced apoptosis in rat glioma C6 cells was investigated. TNF‑α was observed to induce cell apoptosis and the phosphorylation of p38MAPK in C6 cells. In addition, the inhibition of p38MAPK markedly reduced TNF‑α‑induced apoptosis, while JNK inhibition did not affect apoptosis. Furthermore, p38MAPK transfection altered the cell cycle of glioma cells and increased the rate of apoptosis. It also led to an increase in the level of soluble TNF‑α in the culture supernatant and membrane TNF receptor I levels in tumor cells. In conclusion, the results of the current study demonstrated that the activation of p38MAPK mediates TNF‑α‑induced apoptosis in glioma C6 cells, suggesting p38MAPK as a potential target for glioma therapy.

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“…Therefore, it is possible that this augmentation in resting BDNF concentration is linked to an increase in enzymatic profile, which is responsible for extracellular cleavage of BDNF, and physical exercise influences this constitutive context. It has been found that chronic exercise seems to be closely related to activation of matrix metalloproteinases (38) and increased plasmin (16), which is mainly responsible for extracellular cleavage of BDNF (27,41), which are related to angiogenesis processes mediated by increases in serum BDNF concentration (19,20,41).…”

Section: Discussionmentioning

confidence: 99%

Peripheral vascular reactivity and serum BDNF responses to aerobic training are impaired by the BDNF Val66Met polymorphism

Lemos

Alves

Souza

et al. 2016

Physiological Genomics

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-Besides neuronal plasticity, the neurotrophin brain-derived neurotrophic factor (BDNF) is also important in vascular function. The BDNF has been associated with angiogenesis through its specific receptor tropomyosin-related kinase B (TrkB). Additionally, Val66Met polymorphism decreases activity-induced BDNF. Since BDNF and TrkB are expressed in vascular endothelial cells and aerobic exercise training can increase serum BDNF, this study aimed to test the hypotheses: 1) Serum BDNF levels modulate peripheral blood flow; 2) The Val66Met BDNF polymorphism impairs exercise training-induced vasodilation. We genotyped 304 healthy male volunteers (Val66Val, n ϭ 221; Val66Met, n ϭ 83) who underwent intense aerobic exercise training on a running track three times/wk for 4 mo. We evaluated pre-and post-exercise training serum BDNF and proBDNF concentration, heart rate (HR), mean blood pressure (MBP), forearm blood flow (FBF), and forearm vascular resistance (FVR). In the pre-exercise training, BDNF, proBDNF, BDNF/proBDNF ratio, FBF, and FVR were similar between genotypes. After exercise training, functional capacity (V O2 peak) increased and HR decreased similarly in both groups. Val66Val, but not Val66Met, increased BDNF (interaction, P ϭ 0.04) and BDNF/proBDNF ratio (interaction, P Ͻ 0.001). Interestingly, FBF (interaction, P ϭ 0.04) and the FVR (interaction, P ϭ 0.01) responses during handgrip exercise (HG) improved in Val66Val compared with Val66Met, even with similar responses of HR and MBP. There were association between BDNF/proBDNF ratio and FBF (r ϭ 0.64, P Ͻ 0.001) and FVR (r ϭ Ϫ0.58, P Ͻ 0.001) during HG exercise. These results show that peripheral vascular reactivity and serum BDNF responses to exercise training are impaired by the BDNF Val66Met polymorphism and such responsiveness is associated with serum BDNF concentrations in healthy subjects.BDNF Val66Met polymorphism; exercise training; vascular reactivity EXERCISE TRAINING HAS BEEN considered a key element in the improvement in brain-derived neurotrophic factor (BDNF) levels (39), which is the strongest factor linking exercise with cognitive benefits. However, the variability of individual responses may be linked to genetic differences.While BDNF promotes neuronal survival and enhanced synaptic plasticity by activating the tropomyosin kinase B (TrkB) receptor, the action of its precursor proBDNF results in apoptosis by interacting with the p75 neurotrophin receptor (p75NTR), and both are significantly involved in different physiological functions (15,53).Considering the fact that the BDNF gene and its TrkB receptor are expressed in several tissues, such as brain, heart, lungs, and endothelial cells (12, 28), besides neuronal plasticity, it is possible that the neurotrophin BDNF also is involved in the health of other tissues. Indeed, besides the hippocampus, the circulating BDNF is produced by a number of peripheral nonneuronal tissues, including vascular endothelial cells (28,53). Moreover, the neurotrophin BDNF has been associated with angiogenesis thro...

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Apoptosis Signal-Regulating Kinase 1 Is Involved in Brain-Derived Neurotrophic Factor (BDNF)-Enhanced Cell Motility and Matrix Metalloproteinase 1 Expression in Human Chondrosarcoma Cells

Cited by 25 publications

References 58 publications

BDNF promotes activation of astrocytes and microglia contributing to neuroinflammation and mechanical allodynia in cyclophosphamide-induced cystitis

BDNF promotes activation of astrocytes and microglia contributing to neuroinflammation and mechanical allodynia in cyclophosphamide-induced cystitis

p38MAPK activation mediates tumor necrosis factor-α-induced apoptosis in glioma cells

Peripheral vascular reactivity and serum BDNF responses to aerobic training are impaired by the BDNF Val66Met polymorphism

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