scholarly journals Activation of transient receptor potential vanilloid 4 induces apoptosis in hippocampus through downregulating PI3K/Akt and upregulating p38 MAPK signaling pathways

2015 ◽  
Vol 6 (6) ◽  
pp. e1775-e1775 ◽  
Author(s):  
P Jie ◽  
Z Hong ◽  
Y Tian ◽  
Y Li ◽  
L Lin ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
P38 Mapk ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Mapk Signaling ◽  
Transient Receptor Potential Vanilloid ◽  
Transient Receptor ◽  
Mapk Signaling Pathways

scholarly journals Suppression of TRPV1/TRPM8/P2Y Nociceptors by Withametelin via Downregulating MAPK Signaling in Mouse Model of Vincristine-Induced Neuropathic Pain

2021 ◽  
Vol 22 (11) ◽  
pp. 6084
Author(s):  
Adnan Khan ◽  
Bushra Shal ◽  
Ashraf Ullah Khan ◽  
Rahim Ullah ◽  
Muhammad Waleed Baig ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Transient Receptor Potential ◽  
Purinergic Receptor ◽  
Receptor Potential ◽  
B Cell Lymphoma ◽  
Mapk Signaling ◽  
Transient Receptor Potential Vanilloid ◽  
Transient Receptor

Vincristine (VCR) is a widely used chemotherapy drug that induced peripheral painful neuropathy. Yet, it still lacks an ideal therapeutic strategy. The transient receptor potential (TRP) channels, purinergic receptor (P2Y), and mitogen-activated protein kinase (MAPK) signaling play a crucial role in the pathogenesis of neuropathic pain. Withametelin (WMT), a potential Phytosteroid isolated from datura innoxa, exhibits remarkable neuroprotective properties. The present investigation was designed to explore the effect of withametelin on VCR-induced neuropathic pain and its underlying molecular mechanism. Initially, the neuroprotective potential of WMT was confirmed against hydrogen peroxide (H2O2)-induced PC12 cells. To develop potential candidates for neuropathic pain treatment, a VCR-induced neuropathic pain model was established. Vincristine (75 μg/kg) was administered intraperitoneally (i.p.) for 10 consecutive days (day 1–10) for the induction of neuropathic pain. Gabapentin (GBP) (60 mg/kg, i.p.) and withametelin (0.1 and 1 mg/kg i.p.) treatments were given after the completion of VCR injection on the 11th day up to 21 days. The results revealed that WMT significantly reduced VCR-induced pain hypersensitivity, including mechanical allodynia, cold allodynia, and thermal hyperalgesia. It reversed the VCR-induced histopathological changes in the brain, spinal cord, and sciatic nerve. It inhibited VCR-induced changes in the biochemical composition of the myelin sheath of the sciatic nerve. It markedly downregulated the expression levels of TRPV1 (transient receptor potential vanilloid 1); TRPM8 (Transient receptor potential melastatin 8); and P2Y nociceptors and MAPKs signaling, including ERK (Extracellular Signal-Regulated Kinase), JNK (c-Jun N-terminal kinase), and p-38 in the spinal cord. It suppressed apoptosis by regulating Bax (Bcl2-associated X-protein), Bcl-2 (B-cell-lymphoma-2), and Caspase-3 expression. It considerably attenuated inflammatory cytokines, oxidative stress, and genotoxicity. This study suggests that WMT treatment suppressed vincristine-induced neuropathic pain by targeting the TRPV1/TRPM8/P2Y nociceptors and MAPK signaling.

scholarly journals Aconitine Induces TRPV2-Mediated Ca2+ Influx through the p38 MAPK Signal and Promotes Cardiomyocyte Apoptosis

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Chunai Yang ◽  
Xiaoyan Zeng ◽  
Zhongfeng Cheng ◽  
Junbo Zhu ◽  
Yangshan Fu
Keyword(s):  
P38 Mapk ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Mapk Signaling ◽  
Cardiomyocyte Apoptosis ◽  
Dependent Manner ◽  
H9c2 Cardiomyocytes ◽  
Transient Receptor ◽  
Effective Component ◽  
Dose Dependent

Aconitine is the main effective component of traditional Chinese medicine Aconitum, which has been proved to have severe cardiovascular toxicity. The toxic effect of aconitine on cardiomyocytes is related to intracellular calcium overload, but the mechanism remains unclear. The aim of this study was to explore the mechanism of aconitine inducing intracellular Ca2+ overload and promoting H9c2 cardiomyocyte apoptosis through transient receptor potential cation channel subfamily V member 2 (TRPV2). After treated with different concentrations of aconitine, the level of cell apoptosis, intracellular Ca2+, and expression of p-p38 MAPK and TRPV2 of H9c2 cardiomyocytes were detected. The results showed that aconitine induced Ca2+ influx and H9c2 cardiomyocyte apoptosis in a dose-dependent manner and promoted p38 MAPK activation as well as TRPV2 expression and plasma membrane (PM) metastasis. siTRPV2, tranilast, and SB202190 reversed intracellular Ca2+ overload and H9c2 cardiomyocyte apoptosis induced by aconitine. These results suggested that aconitine promoted TRPV2 expression and PM metastasis through p38 MAPK signaling, thus inducing intracellular Ca2+ overload and cardiomyocyte apoptosis. Furthermore, TRPV2 is a potential molecular target for the treatment of aconitine poisoning.

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