• The Korean Journal of Physiology and Pharmacology
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• v.5 no.6
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• pp.451-456
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• 2001

In rat hippocampus, kainic acid (KA; 10 mg/kg; i.p.) increased the phosphorylated forms of ERK1/2 (p-ERK1/2) and Jun kinase1 (p-JNK1), but not p-JNK2 and p38 (p-p38). The preadministration with cycloheximide (CHX; 5 mg/kg; i.p.) inhibited KA-induced increase of p-JNK1, but not p-ERK1/2. Surprisingly, the phosphorylated upstream MAP kinase kinases (p-MKKs) were not correlated with their downstream MAP kinases. The basal p-MKK1/2 levels were completely abolished by KA, which were reversed by CHX. In addition, p-MKK4 and p-MKK3/6 levels were enhanced by CHX alone, but were attenuated by KA. Thus, our results showed that KA increased the p-ERK and p-JNK levels in rat hippocampus, which were not parallel with their classical upstreamal kinases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.5
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• pp.1211-1216
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• 2006

The effect of a chronic programme of either low- or moderate-to-high-intensity treadmill running on the activation of the Extracellular-signal regulated protein kinase (ERK1/2), Phosphorylated ERK 1/2(pERK1/2) and the Phosphorylated c-Jun N-terminal kinase(pJNK) pathways was determined in rat Back skin Hair follicle. Sprague-Dawley rats were assigned to one of three groups: (i) sedentary group(NE; n=10); (ii) low-intensity exercise group (Bm/min; LIE; n=10); and (iii) moderate-high-intensity exercise group(28m1min; HIE; n=10). The training regimens were planned so that animals covered the same distance and had similar utilization for both LIE and HIE exercise sessions. The report runs as follows; A single bout of LIE or HIE following 4 weeks of exercise led to a twofold increase in the phosphorylation of ERK2, pERK2 and a threefold increase in pJNKl, pERKl. ERKI phosphorylation in LIE Back skin sampled and pJNK2 in HIE Back skin sampled 48h after the last exercise bout was similar to sedentary values, while pJNK2 phosphorylation in LIE Back skin sampled was 70-80% lower than sedentary. 48h after the last exercise bout of LIE or HIE increased ERK2, pERKl and pJNKl expression, with the magnitude of this increase being independent of prior exercise intensity or duration. PERK1/2, pJNKl expression was increased Three- to fourfold in Back skin Hair follicle sampled 48h after the last exercise bout irrespective of the prior exercise programme, but ERKI expression in HIE Back skin sampled was approximately 90% lower than sedentary values. In conclusion, exercise-training of different jntensities/durations results in selective postexercise activation of intracellular signal pathways, which may be one mechanism regulating specific adaptations induced by diverse training programmes.

• Journal of Life Science
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• v.21 no.2
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• pp.242-250
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• 2011

Although insulin-like growth factor-I (IGF-I) and androgen receptor (AR) coactivators are well known effectors of skeletal muscle, the molecular mechanism by which signaling pathways integrating AR coactivators and IGF-I in skeletal muscle cells has not been previously examined. In this study, the effects of IGF-I treatment on the gene expression of AR coactivators in the absence of AR ligands and the roles of the p38 MAPK and ERK1/2 signaling pathways in IGF-I-induced AR coactivators induction were examined. C2C12 cells were treated with 250 ng/ml of IGF-I in the presence or absence of specific inhibitors p38 MAPK (SB203580) or ERK1/2 (PD98059). Treatment of C2C12 cells with IGF-I resulted in increased in GRIP-1, SRC-1, and ARA70 protein expression. The levels of GRIP-1, SRC-1, and ARA70 mRNA were also significantly increased after 5min of IGF-I treatment. IGF-I-induced AR coactivator proteins were significantly blocked by pharmacological inhibitors of p38 MAPK and ERK1/2 pathways. However, there was no significant effect of those inhibitors on IGF-I-induced mRNA level of AR coactivators, suggesting that AR coactivators are post-transcriptionally regulated by IGF-I. Furthermore, the present results suggest that IGF-I stimulates the expression of AR coactivators by cooperative activation of the p38 MAPK and ERK1/2 pathways in C2C12 mouse skeletal muscle cells.

• Journal of Ginseng Research
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• v.46 no.3
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• pp.426-434
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• 2022

Aim: This study investigates the effects of ginsenoside Rb1 (GsRb1) on methamphetamine (METH)-induced toxicity in SH-SY5Y neuroblastoma cells and METH-induced conditioned place preference (CPP) in adult Sprague-Dawley rats. It also examines whether GsRb1 can regulate these effects through the NR2B/ERK/CREB/BDNF signaling pathways. Methods: SH-SY5Y cells were pretreated with GsRb1 (20 mM and 40 mM) for 1 h, followed by METH treatment (2 mM) for 24 h. Rats were treated with METH (2 mg/kg) or saline on alternating days for 10 days to allow CPP to be examined. GsRb1 (5, 10, and 20 mg/kg) was injected intraperitoneally 1 h before METH or saline. Western blot was used to examine the protein expression of NR2B, ERK, P-ERK, CREB, P-CREB, and BDNF in the SH-SY5Y cells and the rats' hippocampus, nucleus accumbens (NAc), and prefrontal cortex (PFC). Results: METH dose-dependently reduced the viability of SH-SY5Y cells. Pretreatment of cells with 40 µM of GsRb1 increased cell viability and reduced the expression of METH-induced NR2B, p-ERK, p-CREB and BDNF. GsRb1 also attenuated the expression of METH CPP in a dose-dependent manner in rats. Further, GsRb1 dose-dependently reduced the expression of METH-induced NR2B, p-ERK, p-CREB, and BDNF in the PFC, hippocampus, and NAc of rats. Conclusion: GsRb1 regulated METH-induced neurotoxicity in vitro and METH-induced CPP through the NR2B/ERK/CREB/BDNF regulatory pathway. GsRb1 could be a therapeutic target for treating METH-induced neurotoxicity or METH addiction.

• International Journal of Oral Biology
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• v.31 no.1
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• pp.21-26
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• 2006

Periodontopathogens including Porphyromonas gingivalis interact with host periodontal cells and the excessive subsequent host responses contribute a major part to the development of periodontal diseases. Cyclooxygenase(COX)-2-synthesized $PGE_2$ has detrimental activities in terms of periodontal pathogenesis. The present study investigated induction of COX-2 expression by P. gingivalis in human monocytic THP-1 cells. Live P. gingivalis increased expression of COX-2, but not that of COX-1, which was demonstrated at both mRNA and protein levels. Elevated levels of $PGE_2$ were released from P. gingivalis-infected THP-1 cells. Pharma-cological inhibition of p38 mitogen-activated protein kinase(MAPK) and extracellular signal-regulated kinase(ERK) substantially attenuated P. gingivalis-induced COX-2 mRNA expression. Indeed, activation of p38 MAPK and ERK was observed in P. gingivalis-infected THP-1 cells. Also, P. gingivalis induced activation of nuclear $factor-{\kappa}B\;(NF-{\kappa}B)$ which is an important transcription factor for COX-2. These results suggest that COX-2 expression is up regulated in P. gingivalis-infected monocytic cells, at least in part, via p38 MAPK, ERK, and $NF-{\kappa}B$.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.6
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• pp.595-603
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• 2016

Ribosomal S6 kinase is a family of serine/threonine protein kinases involved in the regulation of cell viability. There are two subfamilies of ribosomal s6 kinase, (p90rsk, p70rsk). Especially, p90rsk is known to be an important downstream kinase of p44/42 MAPK. We investigated the role of p90rsk on ethanol-induced cell proliferation of HepG2 cells. HepG2 cells were treated with 10~50 mM of ethanol with or without ERK and p90rsk inhibitors. Cell viability was measured by MTT assay. The expression of pERK1, NHE1 was measured by Western blots. The phosphorylation of p90rsk was measured by ELISA kits. The expression of Bcl-2 was measured by qRT-PCR. When the cells were treated with 10~30 mM of ethanol for 24 hour, it showed significant increase in cell viability versus control group. Besides, 10~30 mM of ethanol induced increased expression of pERK1, p-p90rsk, NHE1 and Bcl-2. Moreover treatment of p90rsk inhibitor attenuated the ethanol-induced increase in cell viability and NHE1 and Bcl-2 expression. In summary, these results suggest that p90rsk, a downstream kinase of ERK, plays a stimulatory role on ethanol-induced hepatocellular carcinoma progression by activating anti-apoptotic factor Bcl-2 and NHE1 known to regulate cell survival.

• BMB Reports
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• v.49 no.4
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• pp.220-225
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• 2016

Cancer cells have different characteristics due to the genetic differences where these unique features may strongly influence the effectiveness of therapeutic interventions. Here, we show that the spontaneous reactivation of extracellular signalregulated kinase (ERK), distinct from conventional ERK activation, represents a potent mechanism for cancer cell survival. We studied ERK1/2 activation in vitro in SW480 colorectal cancer cells. Although ERK signaling tends to be transiently activated, we observed the delayed reactivation of ERK1/2 in epidermal growth factor (EGF)-stimulated SW480 cells. This effect was observed even after EGF withdrawal. While phosphorylated ERK1/2 translocated into the nucleus following its primary activation, it remained in the cytoplasm during late-phase activation. The inhibition of primary ERK1/2 activation or protein trafficking, blocked reactivation and concurrently increased caspase 3 activity. Our results suggest that the biphasic activation of ERK1/2 plays a role in cancer cell survival; thus, regulation of ERK1/2 activation may improve the efficacy of cancer therapies that target ERK signaling.

• Journal of Microbiology and Biotechnology
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• v.21 no.9
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• pp.903-913
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• 2011

Vibrio parahaemolyticus, which causes gastroenteritis, wound infection, and septicemia, has two sets of type III secretion systems (TTSS), TTSS1 and TTSS2. A TTSS1-deficient vcrD1 mutant of V. parahaemolyticus showed an attenuated cytotoxicity against HEp-2 cells, and a significant reduction in mouse lethality, which were both restored by complementation with the intact vcrD1 gene. V. parahaemolyticus also triggered phosphorylation of mitogen-activated protein kinases (MAPKs) including p38 and ERK1/2 in HEp-2 cells. The ability to activate p38 and ERK1/2 was significantly affected in a TTSS1-deficient vcrD1 mutant. Experiments using MAPK inhibitors showed that p38 and ERK1/2 MAPKs are involved in V. parahaemolyticus-induced death of HEp-2 cells. In addition, caspase-3 and caspase-9 were processed into active forms in V. parahaemolyticus-exposed HEp-2 cells, but activation of caspases was not essential for V. parahaemolyticus-induced death of HEp-2 cells, as shown by both annexin V staining and lactate dehydrogenase release assays. We conclude that secreted protein(s) of TTSS1 play an important role in activation of p38 and ERK1/2 in HEp-2 cells that eventually leads to cell death via a caspase-independent mechanism.

• Journal of Life Science
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• v.29 no.1
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• pp.129-134
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• 2019

In a previous study, we isolated 11 different kinds of compounds from ethyl acetate fractions of lees (jubak) which is a by-product of Korean traditional wine production. These compounds were identified as caffeic acid, coumaric acid, D-mannitol, ferulic acid, hesperetin, hesperidin, naringenin, naringin, sinapic acid, syringic acid, and vanilic acid. To evaluate their anti-inflammatory activities in an in vitro model, nitric oxide (NO) production was measured in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells after the treatment of these cells with each compound. Among the various chemicals, hesperetin and naringenin showed the highest inhibition of NO production in the LPS-activated RAW 264.7 cells. Hesperetin was chosen for further study because of its strong anti-inflammatory activity and because the mechanisms underlying its anti-inflammatory properties still remain unclear. Our results showed that hesperetin dramatically inhibited NO production in a dose-dependent manner as compared with in an LPS-only treated group, without affecting cell viability. In addition, hesperetin reduced the protein expression of the pro-inflammatory gene inducible nitric oxide synthase (iNOS) in a dose-dependent manner, whereas it did not affect cyclooxygenase-2 (COX-2) expression. Furthermore, hesperetin inhibited phosphorylation of p38 mitogen- activated protein kinase (MAPK) and extracellular signal regulated kinase (ERK) 1/2, whereas it did not affect phosphorylation of c-jun N- terminal kinase (JNK). The results indicated that hesperetin regulated the LPS-induced inflammatory response by suppressing p38 MAPK and ERK1/2 signaling. Overall, our results may help to understand the mechanisms underlying the anti-inflammatory activity mediated by hesperetin.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.1
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• pp.76-81
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• 2007

The effect of either low or high intensity four weeks exercise treadmill running on the activation of the extracellular-signal regulated protein kinase (ERK1/2) and the c-Jun N-terminal kinase(JNK) pathways was determined in rat tibialis muscle. Sprague-Dawley rats were assigned to one of three groups: (i) sedentary group(NE; n=10); (ii) low intensity exercise group (8m/min; LIE; n=10); and (iii) high intensity exercise group(28m/min; HIE; n=10). The training regimens were planned so that animals covered the same distance and had similar glycogenutilization for both LIE and HIE exercise sessions. After four weeks exercise, 48 h after the last exercise bout obtained samples. pERK1 increased 1.5 times comparing with the sedentary group in the low intensity group while it increased 11.7 times in high intensity group, in the tibialis of rats. In the low intensity group, pERK2 increased 1.4 times comparing with the sedentary group while it increased 3.3 times in high intensity group. While pJNK1 decreased 0.9 times, comparing with the sedentary group, pJNK2 was increased to 0.5 times in the low intensity group. But in high intensity group, pJNK2 decreased 0.7 times while pJNK1 didn't show any change. In conclusion, Four weeks exercise of different intensities results in tibialis muscle activation of intracellular signal pathways, which may be one mechanism regulating specific adaptations induced by different exercise intensities.