Parthenolide Enhances Cisplatin Sensitivity in Uveal Melanoma by Regulated Mitogen-Activated Protein Kinase Signal Pathway

2021 ◽  
Vol 11 (1) ◽  
pp. 51-58
Author(s):  
Baotong Shu ◽  
Yi Liu ◽  
Yu Ma ◽  
Li Li
Keyword(s):  
Treatment Group ◽  
Protein Kinase ◽  
Cell Line ◽  
Uveal Melanoma ◽  
Cell Activity ◽  
Signal Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Control Group ◽  
Mitogen Activated Protein ◽  
Mapk Signal Pathway

To investigate parthenolide (PTL)’s effect to cisplatin (DDP) sensitivity in uveal melanoma and to show the underlying mechanism. Human uveal melanoma cell line M23 was split into the control group, PTL treatment group, DDP treatment group, PTL + DDP treatment group, DDP + Mitogen-activated protein kinase (MAPK) signal inhibitor (SB203580) treatment group, and PTL + DDP + MAPK signal activator (anisomycin) treatment group. CCK-8 test was conducted to detect cell viability, flow cytometry was utilized for cell apoptosis detection, and western blot was utilized to determine the phosphorylation of p38MAPK and JNK. Compared to the control group, PLT treatment group M23 cell activity, and expression of p-p38MAPK, p-JNK were reduced notably (P < 0.05). Meanwhile, these indices of DDP treatment group were lower than of the control group but higher than of the PTL treatment group. In the PTL + DDP treatment group M23 cell activity and expression level of p-p38MAPK, p-JNK was significantly lower than in the PTL and DDP treatment groups (P < 0.05). Inhibition of MAPK signal pathway increased the DDP effect to proliferation inhibition and apoptosis promotion. In contrast, MAPK signal pathway activator treatment alleviates PTL + DDP treatment effect on M23 cell line apoptosis and proliferation. Parthenolide (PTL) increased cisplatin (DDP) sensitivity in uveal melanoma through the inhibition of MAPK signal pathway.

scholarly journals Correlations between Insulin Receptor Substrate-1 with Phosphoinositide 3-Kinase and P38 Mitogen-Activated Protein Kinase Levels after Treatment of Diabetic Rats with Puguntano (Curanga Fel-Terrae [Merr.]) Leaf Extract

2019 ◽  
Vol 7 (8) ◽  
pp. 1247-1251 ◽  
Author(s):  
Santi Syafril ◽  
Dharma Lindarto ◽  
Aznan Lelo ◽  
Rosita Juwita Sembiring ◽  
Awaluddin Saragih
Keyword(s):  
Treatment Group ◽  
Protein Kinase ◽  
P38 Mapk ◽  
Leaf Extract ◽  
Mitogen Activated Protein Kinase ◽  
Control Group ◽  
Insulin Receptor Substrate ◽  
Mitogen Activated Protein ◽  
Positive Correlations ◽  
Phosphoinositide 3 Kinase

BACKGROUND: Defects in post-receptor insulin signalling are the major cause of insulin resistance in type 2 diabetes mellitus (T2DM). AIM: This study aimed to investigate the correlations between insulin receptor substrate (IRS)-1 with phosphoinositide 3-kinase (PI3K) and p38 mitogen-activated protein kinase (MAPK) levels after puguntano (Curanga fel-terrae [Merr.]) leaf extract treatment in a rat model of T2DM. METHODS: A combination of high-fat diet-feeding (HFD) and multiple low dose intraperitoneal injections of streptozotocin was used to induced T2DM in 48 Wistar rats, which were then randomly divided into control and treatment groups (n = 24 per group). Puguntano leaf extract was administered to the treatment group once daily (200 mg/kg.bw) for 10 days. IRS-1, PI3K and p38 MAPK levels were measured in skeletal muscle using sandwich ELISAs in control group after becoming T2DM and in the treatment group after 10 days of puguntano treatment. Data were analysed using the Wilcoxon test and Spearman’s correlation. RESULTS: IRS-1, PI3K and p38 MAPK levels were significantly higher in the treatment group than in the control group. There were also significant positive correlations between IRS-1 with PI3K and p38 MAPK levels (r = 0.375, p = 0.035; r = 0.552, p = 0.003; respectively) after the treatment. CONCLUSION: This study demonstrated significant positive correlations between IRS-1 with PI3K and p38 MAPK levels after puguntano leaf extract treatment of T2DM rats.

scholarly journals Ghrelin exerts a proliferative effect on a rat pituitary somatotroph cell line via the mitogen-activated protein kinase pathway

2004 ◽  
pp. 233-240 ◽  
Author(s):  
AM Nanzer ◽  
S Khalaf ◽  
AM Mozid ◽  
RC Fowkes ◽  
MV Patel ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Protein Kinase ◽  
Cell Line ◽  
Kinase Inhibitor ◽  
Thymidine Incorporation ◽  
Mapk Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Gh3 Cells ◽  
Rat Pituitary ◽  
Mitogen Activated Protein

OBJECTIVES: Ghrelin is a brain-gut peptide with GH-releasing and appetite-inducing activities and a widespread tissue distribution. Ghrelin is the endogenous ligand of the GH secretagogue receptor type 1a (GHS-R1a), and both ghrelin and the GHS-R1a are expressed in the pituitary. There are conflicting data regarding the effects of ghrelin on cell proliferation. A positive effect on proliferation and activation of the mitogen-activated protein kinase (MAPK) pathway has been found in hepatoma, adipose, cardiomyocyte and prostate cell lines. However, ghrelin has also been shown to have anti-proliferative effects on breast, lung and thyroid cell lines. We therefore examined the effect of ghrelin on the rat pituitary cell line GH3. METHODS: RT-PCR was used for the detection of GHS-R1a and pre-proghrelin mRNA expression in GH3 cells. The effect of ghrelin on cell proliferation was studied using [(3)H]thymidine incorporation; cell counting and the activation of the MAPK pathway were studied using immunoblotting and inhibitors of the extracellular signal-regulated kinase 1 and 2 (ERK 1/2), protein kinase C (PKC) and tyrosine phosphatase pathways. RESULTS: GHS-R1a and ghrelin mRNA expression were detected in GH3 cells. Ghrelin, at 10(-10) to 10(-6) M concentrations, significantly increased [(3)H]thymidine incorporation (at 10(-9) M, 183+/-13% (means+/-s.e.m.) compared with untreated controls), while 12-phorbol 13-myristate acetate (PMA) at 10(-7) M (used as a positive control) caused a 212+/-14% increase. A reproducible stimulatory effect of desoctanoyl ghrelin was also observed on [(3)H]thymidine incorporation (135+/-5%; P<0.01 at 10(-9) M compared with control), as well as on the cell count (control 6.8 x 10(4)+/-8.7 x 10(3) cells/ml vs desoctanoyl ghrelin (10(-9) M) 1.04 x 10(5)+/-7.5 x 10(3) cells/ml; P<0.01). Ghrelin caused a significant increase in phosphorylated ERK 1/2 in immunoblotting, while desoctanoyl ghrelin showed a smaller but also significant stimulatory effect. The positive effect of ghrelin and desoctanoyl ghrelin on [(3)H]thymidine incorporation was abolished by the MAPK kinase inhibitor U0126, the PKC inhibitor GF109203X and the tyrosine kinase inhibitor tyrphostin 23, suggesting that the ghrelin-induced cell proliferation of GH3 cells is mediated both via a PKC-MAPK-dependent pathway and via a tyrosine kinase-dependent pathway. This could also be clearly demonstrated by Western blot analysis, where a transient increase in ERK 1/2 phosphorylation by ghrelin was attenuated by all three inhibitors. CONCLUSION: We have shown a novel role for ghrelin in stimulating the proliferation of a somatotroph pituitary tumour cell line, suggesting that ERK activation is involved in mediating the effects of ghrelin on cell proliferation. Desoctanoyl ghrelin showed a similar effect. As ghrelin has been shown to be expressed in both normal and adenomatous pituitary tissue, locally produced ghrelin may play a role in pituitary tumorigenesis via an autocrine/paracrine pathway.

Preparation of Snake Neurotoxin Nanocapsules and the Analgesic Mechanism of P38 Mitogen-Activated Protein Kinase Signal Pathway Combining Snake Neurotoxin Nanocapsules with Gabapentin

2021 ◽  
Vol 13 (3) ◽  
pp. 463-472
Author(s):  
Fengting Yin ◽  
Xiaokun Li ◽  
Weili Zhang
Keyword(s):  
Neuropathic Pain ◽  
Protein Kinase ◽  
Signaling Pathway ◽  
Glycolic Acid ◽  
Mapk Signaling ◽  
Signal Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Water Phase ◽  
Mitogen Activated Protein ◽  
Snake Neurotoxin

This study aimed to explore the analgesic effect of snake neurotoxin combined with gabapentin (Gab) on neuropathic pain in rats with chronic compression injury (CCI) of the sciatic nerve based on the nanotechnology. Firstly, various solutions were prepared to obtain the inner water phase, the oil phase, the outer water phase, and the dilution phase. Poly(lactic-co-glycolic) Acid (PLGA) and polyethylene glycol-poly(lactic-co-glycolic) acid (PEG-PLGA) were added to the prepared oil phase solution to obtain the PLGA snake neurotoxin nanocapsule and PEG-PLGA snake neurotoxin nanocapsule, respectively. After the nanocapsules were obtained, a rat CCI model was further modelled, and the reactive oxygen species (ROS) content in the rat brain tissue was analyzed and tested by the kit, and the optimal physical conditions for preparing the nanocapsules were tested. In order to test the effect of nanocapsules on the p38 mitogen-activated protein kinase (MAPK) signaling pathway, the rats were divided into Control group, Sham group, CCI group, Gabapentin (Gab) group, and PEG-PLGA snake neurotoxin nanocapsule + Gab group. The rats in different groups were given abdominal injections to compare relevant indicators of signal pathway. In the experiment, neuropathic pain was related to changes in ROS content, and snake neurotoxin nanocapsules could reduce the ROS content; PLGA snake neurotoxin nanocapsules and PEG-PLGA snake neurotoxin nanocapsules had encapsulation efficiencys of 24.7% and 22.8% and drug loading of 3.28% and 3.02%, respectively, and the particle sizes of prepared nanocapsules were 760 nm~1,150 nm. Besides, the phase transition temperature of about 50 °C and the light time of 1 h can accelerate the release of nanocapsules to the greatest extent; and the snake neurotoxin could inhibit the activation of p38 MAPK signaling pathway so as to play the analgesic effects on neuropathic pain.

scholarly journals Heterogeneity in Mitogen-Activated Protein Kinase (MAPK) Pathway Activation in Uveal Melanoma With Somatic GNAQ and GNA11 Mutations

2019 ◽  
Vol 60 (7) ◽  
pp. 2474 ◽  
Author(s):  
Getachew Boru ◽  
Colleen M. Cebulla ◽  
Klarke M. Sample ◽  
James B. Massengill ◽  
Frederick H. Davidorf ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Uveal Melanoma ◽  
Mapk Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Pathway Activation ◽  
Mitogen Activated Protein

scholarly journals A-Type Cinnamon Procyanidin Oligomers Protect Against 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Neurotoxicity in Mice Through Inhibiting the P38 Mitogen-Activated Protein Kinase/P53/BCL-2 Associated X Protein Signaling Pathway

2020 ◽  
Vol 150 (7) ◽  
pp. 1731-1737
Author(s):  
Qi Xu ◽  
Ziyu Chen ◽  
Borong Zhu ◽  
Gaorui Wang ◽  
Qi Jia ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Motor Behavior ◽  
Neurodegenerative Disorder ◽  
Mitogen Activated Protein Kinase ◽  
Saline Control ◽  
Control Group ◽  
X Protein ◽  
Neuroprotective Effects ◽  
Mitogen Activated Protein ◽  
Underlying Mechanisms

ABSTRACT Background Parkinson's disease (PD) is a common neurodegenerative disorder. Cinnamon procyanidin oligomers (CPOs) are flavonoids with many claimed health benefits. Objective This study aimed to elucidate the neuroprotection of A-type CPOs (CPO-A) and the underlying mechanisms in cultured cell and animal models of PD. Methods Thirty male mice (C57BL/6, 9-wk old) were assigned to 3 groups (n = 10), and were given daily gavage of saline [control and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) groups] or CPO-A (150 mg/kg, CPO-A group) during days 1–15 and daily intraperitoneal injections of saline (control group) or MPTP (20 mg/kg; MPTP and MPTP + CPO-A groups) during days 11–15. After the motor behavior test, all mice were killed on day 16 to collect the substantia nigra (SN) for assaying the neuroprotective effects of CPO-A. SH-SY5Y cells were treated with 12.5 μM CPO-A for 2 h or 3 activators of stress-related kinases (5–25 μM) for 12–48 h followed by 1 mM 1-methyl-4-phenylpyridinium (MPP+) for assays of viability, morphology, and stress status. Results Compared with the control, the MPTP treatment decreased (P &lt; 0.05) locomotor activity by 21%, and tyrosine hydroxylase (TH) positive neurons by 55% and Th mRNA concentration by 51% in the SN. The CPO-A treatment attenuated or restored (P &lt; 0.05) these changes and inhibited (P &lt; 0.05) the MPTP-induced activation of P38 mitogen-activated protein kinase (P38MAPK) and P53, along with the downstream expression of BCL-2 associated X protein (BAX) in the SN. In SH-SY5Y cells, the CPO-A treatment blocked (P &lt; 0.01) the MPP+-induced accumulation of intracellular reactive oxygen species and neurotoxicity. However, this protection was abolished (P &lt; 0.05) by activators of the P38MAPK/P53/BAX pathway. Conclusion CPO-A protected against MPP+-induced cytotoxicity in SH-SY5Y cells and MPTP-induced neurotoxicity in mice by regulating the P38MAPK/P53/BAX signaling. Our findings reveal a novel role and mechanism of a food flavonoid CPO-A in preventing neurodegeneration.

Synergistic Activation of Mitogen-Activated Protein Kinase by Cyclic AMP and Myeloid Growth Factors Opposes Cyclic AMP’s Growth-Inhibitory Effects

Blood ◽  
1999 ◽  
Vol 93 (2) ◽  
pp. 537-553 ◽  
Author(s):  
Angel Wai-mun Lee
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Cell Line ◽  
Mapk Pathway ◽  
Dominant Negative ◽  
Mitogen Activated Protein Kinase ◽  
Erk Activation ◽  
Mitogen Activated Protein ◽  
Erk Activity ◽  
Myeloid Progenitors

Abstract Colony-stimulating factors (CSFs) promote the proliferation, differentiation, commitment, and survival of myeloid progenitors, whereas cyclic AMP (cAMP)-mediated signals frequently induce their growth arrest and apoptosis. The ERK/mitogen-activated protein kinase (MAPK) pathway is a target for both CSFs and cAMP. We investigated how costimulation by cAMP and colony-stimulating factor-1 (CSF-1) or interleukin-3 (IL-3) modulates MAPK in the myeloid progenitor cell line, 32D. cAMP dramatically increased ERK activity in the presence of CSF-1 or IL-3. IL-3 also synergized with cAMP to activate ERK in another myeloid cell line, FDC-P1. The increase in ERK activity was transmitted to a downstream target, p90rsk. cAMP treatment of 32D cells transfected with oncogenic Ras was found to recapitulate the superactivation of ERK seen with cAMP and CSF-1 or IL-3. ERK activation in the presence of cAMP did not appear to involve any of the Raf isoforms and was blocked by expression of dominant-negative MEK1 or treatment with a MEK inhibitor, PD98059. Although cAMP had an overall inhibitory effect on CSF-1–mediated proliferation and survival, the inhibition was markedly increased if ERK activation was blocked by PD98059. These findings suggest that upregulation of the ERK pathway is one mechanism induced by CSF-1 and IL-3 to protect myeloid progenitors from the growth-suppressive and apoptosis-inducing effects of cAMP elevations.

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