PEP-1-GLRX1 Protein Exhibits Anti-Inflammatory Effects by Inhibiting the Activation of MAPK and NF-κB Pathways in Raw 264.7 Cells

Shin, Min Jea; Kim, Dae Won; Choi, Yeon Joo; Ju, Hyun; Lee, Sung Ho; Park, Jinseu; Han, Kyu Hyung; Eum, Won Sik; Choi, Soo Young

doi:10.5483/bmbrep.2020.53.2.180

Cited by 11 publications

(9 citation statements)

References 55 publications

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“…Moreover, the MAPK pathway has been considered a typical molecular target for developing anti-inflammatory agents [ 46 ]. The activation of MAPKs has been reported to upregulate pro-inflammatory mediators [ 47 , 48 ]. Our results partially support these findings in that the treatment of PC inhibits the phosphorylation levels of ERK and JNK.…”

Section: Discussionmentioning

confidence: 99%

The Anti-Inflammatory and the Antinociceptive Effects of Mixed Agrimonia pilosa Ledeb. and Salvia miltiorrhiza Bunge Extract

Feng

Kim

Sim

et al. 2021

Plants

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Arthritis is a common condition that causes pain and inflammation in a joint. Previously, we reported that the mixture extract (ME) from Agrimonia pilosa Ledeb. (AP) and Salvia miltiorrhiza Bunge (SM) could ameliorate gout arthritis. In the present study, we aimed to investigate the potential anti-inflammatory and antinociceptive effects of ME and characterize the mechanism. We compared the anti-inflammatory and antinociceptive effects of a positive control, Perna canaliculus powder (PC). The results showed that one-off and one-week treatment of ME reduced the pain threshold in a dose-dependent manner (from 10 to 100 mg/kg) in the mono-iodoacetate (MIA)-induced osteoarthritis (OA) model. ME also reduced the plasma TNF-α, IL-6, and CRP levels. In LPS-stimulated RAW 264.7 cells, ME inhibited the release of NO, PGE2, LTB4, and IL-6, increased the phosphorylation of PPAR-γ protein, and downregulated TNF-α and MAPKs proteins expression in a concentration-dependent (from 1 to 100 µg/mL) manner. Furthermore, ME ameliorated the progression of ear edema in mice. In most of the experiments, ME-induced effects were almost equal to, or were higher than, PC-induced effects. Conclusions: The data presented here suggest that ME shows anti-inflammatory and antinociceptive activities, indicating ME may be a potential therapeutic for arthritis treatment.

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Section: Discussionmentioning

confidence: 99%

The Anti-Inflammatory and the Antinociceptive Effects of Mixed Agrimonia pilosa Ledeb. and Salvia miltiorrhiza Bunge Extract

Feng

Kim

Sim

et al. 2021

Plants

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“…Although GLRX1 is used to treat neuronal diseases, the therapeutic application is limited by its inability to transduce into cells. To resolve the protein delivery challenges, cell-permeable PTD-fused proteins are used in therapeutic protein applications for various diseases [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. Therefore, in the present study, we prepared a cell-permeable PEP-1-GLRX1 and investigated whether this fusion protein inhibited dopaminergic neuronal cell death in MPP + - and MPTP-induced cytotoxicity.…”

Section: Discussionmentioning

confidence: 99%

“…All antibodies used in Western blotting were obtained from Cell Signaling Technology (Beverly, MA, USA) except histidine antibody (Santa Cruz Biotechnology; Santa Cruz, CA, USA). PEP-1-GLRX1 protein was purified as previously described [ 27 , 33 ]. PEP-1 peptides were purchased from PEPTRON (Daejeon, Korea).…”

Section: Methodsmentioning

confidence: 99%

“…It is well known that protein transduction domains (PTD) can deliver proteins across the plasma membrane into cells and brain crossing the BBB [21,22]. These transduced PTD fusion proteins inhibited cell death [23][24][25][26][27][28][29][30][31][32]. In this study, we examined whether cell permeable PTD-fused PEP-1-GLRX1 protein inhibited dopaminergic neuronal cell death induced by MPP + -and MPTP-treated cells in a PD animal model.…”

Section: Introductionmentioning

confidence: 99%

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PEP-1-GLRX1 Reduces Dopaminergic Neuronal Cell Loss by Modulating MAPK and Apoptosis Signaling in Parkinson’s Disease

et al. 2021

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Parkinson’s disease (PD) is characterized mainly by the loss of dopaminergic neurons in the substantia nigra (SN) mediated via oxidative stress. Although glutaredoxin-1 (GLRX1) is known as one of the antioxidants involved in cell survival, the effects of GLRX1 on PD are still unclear. In this study, we investigated whether cell-permeable PEP-1-GLRX1 inhibits dopaminergic neuronal cell death induced by 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We showed that PEP-1-GLRX1 protects cell death and DNA damage in MPP+-exposed SH-SY5Y cells via the inhibition of MAPK, Akt, and NF-κB activation and the regulation of apoptosis-related protein expression. Furthermore, we found that PEP-1-GLRX1 was delivered to the SN via the blood–brain barrier (BBB) and reduced the loss of dopaminergic neurons in the MPTP-induced PD model. These results indicate that PEP-1-GLRX1 markedly inhibited the loss of dopaminergic neurons in MPP+- and MPTP-induced cytotoxicity, suggesting that this fusion protein may represent a novel therapeutic agent against PD.

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“…SARS-CoV-2-infected Calu-3 cells were lysed with cell lysis buffer (20 mM Tris-HCl, pH 8.0, 5 mM EDTA, 150 mM NaCl, 100 mM NaF, 2 mM Na3VO4, and 1% NP-40) and the cell lysates were run on SDS-PAGE and subsequently transferred onto a nitrocellulose membrane as described previously (22,34), and detailed information is provided in the Supplementary Material.…”

Section: Western Blottingmentioning

confidence: 99%

MUC1-C influences cell survival in lung adenocarcinoma Calu-3 cells after SARS-CoV-2 infection

Maharjan

Park

Kim

et al. 2021

BMB Rep

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces coronavirus disease 2019 (COVID-19) and may increase the risk of adverse outcomes in lung cancer patients. In this study, we investigated the expression and function of mucin 1 (MUC1) after SARS-CoV-2 infection in the lung epithelial cancer cell line Calu-3. MUC1 is a major constituent of the mucus layer in the respiratory tract and contributes to pathogen defense. SARS-CoV-2 infection induced MUC1 C-terminal subunit (MUC1-C) expression in a STAT3 activation-dependent manner. Inhibition of MUC1-C signaling increased apoptosis-related protein levels and reduced proliferation-related protein levels; however, SARS-CoV-2 replication was not affected. Together, these results suggest that increased MUC1-C expression in response to SARS-CoV-2 infection may trigger the growth of lung cancer cells, and COVID-19 may be a risk factor for lung cancer patients. [BMB Reports 2021; 54(8): 425-430]

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PEP-1-GLRX1 Protein Exhibits Anti-Inflammatory Effects by Inhibiting the Activation of MAPK and NF-κB Pathways in Raw 264.7 Cells

Cited by 11 publications

References 55 publications

The Anti-Inflammatory and the Antinociceptive Effects of Mixed Agrimonia pilosa Ledeb. and Salvia miltiorrhiza Bunge Extract

The Anti-Inflammatory and the Antinociceptive Effects of Mixed Agrimonia pilosa Ledeb. and Salvia miltiorrhiza Bunge Extract

PEP-1-GLRX1 Reduces Dopaminergic Neuronal Cell Loss by Modulating MAPK and Apoptosis Signaling in Parkinson’s Disease

MUC1-C influences cell survival in lung adenocarcinoma Calu-3 cells after SARS-CoV-2 infection

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