[go: up one dir, main page]
More Web Proxy on the site http://driver.im/
You seem to have javascript disabled. Please note that many of the page functionalities won't work as expected without javascript enabled.
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.1
4.9
Journals
IJMS
Special Issues
Programmed Cell Death and Oxidative Stress: 3rd Edition
ijms-logo
Submit to Special Issue Submit Abstract to Special Issue Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Programmed Cell Death and Oxidative Stress: 3rd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 20 July 2025 | Viewed by 1695

Special Issue Editor

Dr. Takuya Noguchi

E-Mail Website
Guest Editor
Department of Biopharmaceutical Science, Tohoku University, Sendai 980-8578, Japan
Interests: apoptosis; signaling pathways; phosphorylation; signal transduction; cell signaling; reactive oxygen species; molecular cell biology; cell biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous Special Issue “Programmed Cell Death and Oxidative Stress 2.0” (https://www.mdpi.com/journal/ijms/special_issues/94P8FIF763).

Cells that constitute aerobic organisms are continuously exposed to reactive oxygen species (ROS), whose accumulation often initiates oxidative stress. Importantly, oxidative stress plays a critical role in the determination of cell fate by inducing cellular responses, such as proliferation, differentiation, and programmed cell death. Accumulating evidence indicates that oxidative stress initiates various forms of programmed cell death including apoptosis, necroptosis, pyroptosis, parthanatos, and ferroptosis. Moreover, all types of oxidative-stress-induced cell death are closely associated with a wide variety of diseases. For this Special Issue, studies of a wide range of signaling mechanisms and pathological processes related to oxidative stress-induced cell death are welcome.

Dr. Takuya Noguchi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • oxidative stress
  • programmed cell death
  • cellular stresses
  • senescence
  • cytotoxicity
  • cancer
  • neurodegenerative disease
  • inflammatory disease
  • organelle stress

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue policies can be found here.

Related Special Issues

Published Papers (2 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

17 pages, 5547 KiB  
Article
The Selective 3-MST Inhibitor I3MT-3 Works as a Potent Caspase-1 Inhibitor
by Kohei Otani, Ryuto Komatsu, Takuya Noguchi, Wakana Suzuki, Yusuke Hirata and Atsushi Matsuzawa
Int. J. Mol. Sci. 2025, 26(5), 2237; https://doi.org/10.3390/ijms26052237 - 2 Mar 2025
Viewed by 366
Abstract
I3MT-3 (HMPSNE) has been identified as a selective inhibitor of the supersulfide-producing enzyme 3-MST. In this study, we found that I3MT-3 inhibits inflammatory responses, including the secretion of the pro-inflammatory cytokine interleukin-1β (IL-1β) and inflammatory cell death pyroptosis, induced by the activation of [...] Read more.
I3MT-3 (HMPSNE) has been identified as a selective inhibitor of the supersulfide-producing enzyme 3-MST. In this study, we found that I3MT-3 inhibits inflammatory responses, including the secretion of the pro-inflammatory cytokine interleukin-1β (IL-1β) and inflammatory cell death pyroptosis, induced by the activation of the inflammasomes composed of NLRP1, NLRP3, or AIM2. However, interestingly, the knockdown of 3-MST did not affect the activation of the inflammasomes, suggesting that the inhibitory effect of I3MT-3 on inflammasome activation is mediated by alternative ways rather than the inhibition of 3-MST. Interestingly, an in vitro caspase assay revealed that I3MT-3 directly inhibits caspase-1 activation, and molecular docking simulations raised the possibility that the pyrimidone ring in I3MT-3 stabilizes direct interaction of I3MT-3 with caspase-1. Taken together, our data suggest that I3MT-3 inhibits inflammasome activation by targeting caspase-1, and show I3MT-3 as a potent inhibitor of caspase-1. Full article
(This article belongs to the Special Issue Programmed Cell Death and Oxidative Stress: 3rd Edition)
►▼ Show Figures

Figure 1

Figure 1
<p>I3MT-3 inhibits inflammatory responses induced by the inflammasomes. (<b>A</b>) Structural formula of I3MT-3. (<b>B</b>) PMA-differentiated THP-1 cells were cotreated with the indicated concentrations of I3MT-3 or VX-765 (a caspase-1 inhibitor used as a positive control that inhibits Alum-induced IL-1β release), and 200 μg/mL Alum for 4 h [<a href="#B22-ijms-26-02237" class="html-bibr">22</a>]. Cell-free supernatants (Sup) and cell lysates were subjected to immunoblotting with the indicated antibodies. (<b>C</b>) PMA-differentiated THP-1 cells were pretreated with the indicated concentrations of I3MT-3 for 1 h and then treated with 40 μg/mL PMB for 2 h. Cell-free supernatants (Sup) and cell lysates were subjected to immunoblotting with the indicated antibodies. (<b>D</b>) PMA-differentiated THP-1 cells were cotreated with the indicated concentrations of I3MT-3 and 3 μg/mL Poly dA:dT for 4 h. Cell-free supernatants (Sup) and cell lysates were subjected to immunoblotting with the indicated antibodies. (<b>E</b>) PMA-differentiated THP-1 cells were pretreated with the indicated concentrations of I3MT-3 for 1 h and then treated with 1 μM Talabostat for 3 h. Cell-free supernatants (Sup) and cell lysates were subjected to immunoblotting with the indicated antibodies. (<b>F</b>,<b>G</b>) PMA-differentiated THP-1 cells were cotreated with the indicated concentrations of I3MT-3, or VX-765 as a positive control, and 200 μg/mL Alum for 4 h (<b>F</b>), or 3 μg/mL Poly dA:dT for 4 h (<b>G</b>). IL-1β release was analyzed by ELISA. Data shown are the mean ± S.D. Significant differences were determined by one-way ANOVA, followed by the Tukey–Kramer test; *** <span class="html-italic">p</span> &lt; 0.001, ** <span class="html-italic">p</span> &lt; 0.01, * <span class="html-italic">p</span> &lt; 0.05, N.S. not significant. (<b>H</b>) PMA-differentiated THP-1 cells were pretreated with the indicated concentrations of I3MT-3 for 1 h and then treated with 1 μM Talabostat for 3 h. IL-1β release was analyzed by ELISA. Data shown are the mean ± S.D. Significant differences were determined by one-way ANOVA, followed by the Tukey–Kramer test; *** <span class="html-italic">p</span> &lt; 0.001, ** <span class="html-italic">p</span> &lt; 0.01. (<b>I</b>,<b>J</b>) BMDMs were treated with the indicated concentrations of I3MT-3 and 100 ng/mL LPS for 4 h, and then treated with 5 μM nigericin for 1.5 h (<b>I</b>), or 1 mM ATP for 1.5 h (<b>J</b>). IL-1β release was analyzed by ELISA. Data shown are the mean ± S.D. Significant differences were determined by one-way ANOVA, followed by the Tukey–Kramer test; *** <span class="html-italic">p</span> &lt; 0.001. (<b>K</b>) The inhibitory effect of I3MT-3 on inflammatory cell death. PMA-differentiated THP-1 cells were cotreated with the indicated concentrations of I3MT-3 and 200 μg/mL Alum for 4 h. Cell cytotoxicity was measured by LDH release assay. Data shown are the mean ± S.D. Significant differences were determined by one-way ANOVA, followed by the Tukey–Kramer test; *** <span class="html-italic">p</span> &lt; 0.001, ** <span class="html-italic">p</span> &lt; 0.01. (<b>L</b>) Mice were treated with 1 µg LPS and 20 mg/kg I3MT-3 by intraperitoneal injection (IP) for 2 h, and then treated with 20 mg/kg gefitinib by IP. After 1 h, peritoneal lavage fluid was collected, and IL-1β levels were analyzed by ELISA. Data shown are the mean ± S.D. (<span class="html-italic">n</span> = 3). Significant differences were determined by one-way ANOVA, followed by the Tukey–Kramer test; ** <span class="html-italic">p</span> &lt; 0.01, * <span class="html-italic">p</span> &lt; 0.05.</p> Full article ">Figure 2
<p>I3MT-3 inhibits inflammasome activation independently of 3-MST inhibition. (<b>A</b>) PMA-differentiated control or 3-MST KD THP-1 cells were cotreated with 50 μM I3MT-3 and 200 μg/mL Alum for 4 h. Cell-free supernatants (Sup) and cell lysates were subjected to immunoblotting with the indicated antibodies. (<b>B</b>,<b>C</b>) PMA-differentiated control or 3-MST KD THP-1 cells were cotreated with 50 μM I3MT-3 and 200 μg/mL Alum for 4 h (<b>B</b>), or 3 μg/mL Poly dA:dT for 4 h (<b>C</b>). IL-1β release was analyzed by ELISA. Data shown are the mean ± S.D. Significant differences were determined by one-way ANOVA, followed by the Tukey–Kramer test; *** <span class="html-italic">p</span> &lt; 0.001, ** <span class="html-italic">p</span> &lt; 0.01, * <span class="html-italic">p</span> &lt; 0.05. (<b>D</b>) PMA-differentiated control or 3-MST KD THP-1 cells were pretreated with 50 μM I3MT-3 for 1 h and then treated with 1 μM Talabostat for 3 h. IL-1β release was analyzed by ELISA. Data shown are the mean ± S.D. Significant differences were determined by one-way ANOVA, followed by the Tukey–Kramer test; *** <span class="html-italic">p</span> &lt; 0.001. (<b>E</b>,<b>F</b>) PMA-differentiated THP-1 cells were pretreated with the indicated concentrations of TFA (<b>E</b>) or PAG for 24 h (<b>F</b>), and then treated with 200 μg/mL Alum for 4 h. Cell-free supernatants (Sup) and cell lysates were subjected to immunoblotting with the indicated antibodies.</p> Full article ">Figure 3
<p>I3MT-3 does not affect the transcriptional upregulation of pro-IL-1β. (<b>A</b>) PMA-differentiated THP-1 cells were treated with the indicated concentrations of I3MT-3 or 10 μM ML120B for 6 h. Cell lysates were subjected to immunoblotting with the indicated antibodies. (<b>B</b>,<b>C</b>) PMA-differentiated THP-1 cells were treated with the indicated concentrations of I3MT-3 or 10 μM ML120B for 6 h. qRT-PCR was performed, with relative mRNA levels of IL-6 (<b>B</b>) or TNF-α (<b>C</b>). Data shown are the mean ± S.D. Significant differences were determined by one-way ANOVA, followed by the Tukey–Kramer test; *** <span class="html-italic">p</span> &lt; 0.001, ** <span class="html-italic">p</span> &lt; 0.01, N.S. not significant. (<b>D</b>) HEK293-TLR4 cells were pretreated with the indicated concentrations of I3MT-3 or 10 μM ML120B for 4 h and then treated with 100 ng/mL LPS for 4 h. Cell lysates were subjected to immunoblotting with the indicated antibodies. (<b>E</b>) HEK293-TLR4 cells were transfected with a plasmid and a Renilla luciferase plasmid for normalization. After 24 h, cells were pretreated with the indicated concentrations of I3MT-3 or 10 μM ML120B for 4 h and then treated with 100 ng/mL LPS for 4 h. Firefly and Renilla luciferase activities were quantified with a dual-luciferase assay kit. Data shown are the mean ± S.D. Significant differences were determined by one-way ANOVA, followed by the Tukey–Kramer test; ** <span class="html-italic">p</span> &lt; 0.01, * <span class="html-italic">p</span> &lt; 0.05, N.S. not significant.</p> Full article ">Figure 4
<p>I3MT-3 exerts an inhibitory effect on inflammasome activation by targeting caspase-1 but not ASC. (<b>A</b>,<b>B</b>) HEK293A cells were transfected with plasmids of pro-caspase-1 and pro-IL-1β for 6 h, followed by overnight treatment with the above concentrations of I3MT-3. Cell-free supernatants (Sup) and cell lysates were subjected to immunoblotting with the indicated antibodies (<b>A</b>). IL-1β release was analyzed by ELISA (<b>B</b>). Data shown are the mean ± S.D. Significant differences were determined by one-way ANOVA, followed by the Tukey–Kramer test; *** <span class="html-italic">p</span> &lt; 0.001. (<b>C</b>) BMDMs were treated with the indicated concentrations of I3MT-3 and 100 ng/mL LPS for 4 h, and then treated with 1 mM ATP for 1.5 h. Cell-free supernatants (Sup) and cell lysates were subjected to immunoblotting with the indicated antibodies. (<b>D</b>) PMA-differentiated ASC KO THP-1 cells were pretreated with 50 µM I3MT-3 for 1 h and then treated with 1 μM Talabostat for 3 h. Cell-free supernatants (Sup) and cell lysates were subjected to immunoblotting with the indicated antibodies. (<b>E</b>) HEK293A cells were transfected with plasmids of Flag-pro-caspase-1 for 24 h and then treated with 50 μM I3MT-3 or 50 μM VX-765 for 4 h. Purified Flag-caspase-1 was incubated for 20 min at RT in assay buffer. Then Ac-WEHD-pNA Colorimetric substrate 100 µM was added, and it was incubated at 37 °C for 2 h. Activity was measured using a microplate reader and the absorbance was read at 405 nm. Data shown are the mean ± S.D. Significant differences were determined by one-way ANOVA, followed by the Tukey–Kramer test; *** <span class="html-italic">p</span> &lt; 0.001. (<b>F</b>) HT1080 cells were pretreated with the indicated concentrations of I3MT-3 for 24 h and then treated with 50 ng/mL FasL for 4 h. Cell lysates were subjected to immunoblotting with the indicated antibodies. (<b>G</b>) HEK293A cells were transfected with plasmids of Flag-pro-caspase-3 for 24 h and then treated with 50 μM I3MT-3 or 20 μM z-VAD-fmk for 4 h. Caspase-3 activity was measured by the Colorimetric caspase-3 assay. Data are shown as the ratio of caspase-3 activity versus the corresponding controls. Data shown are the mean ± S.D. Significant differences were determined by one-way ANOVA, followed by the Tukey–Kramer test; *** <span class="html-italic">p</span> &lt; 0.001, N.S. not significant.</p> Full article ">Figure 5
<p>(<b>A</b>,<b>B</b>) Molecular docking to predict the binding of I3MT-3 to caspase-1 via AutoDock Vina, the results were visualized by PyMOL. The predicted binding conformation of caspase-1-I3MT-3 (<b>A</b>) and of caspase-1-VX-765 (<b>B</b>) are shown.</p> Full article ">Figure 6
<p>Schematic model to explain our study. I3MT-3 inhibits mature IL-1β release and pyroptosis associated with inflammasome activation. Mechanistically, I3MT-3 selectively inhibits the activity of caspase-1, an essential protein common to all inflammasomes such as NLRP3, AIM2, and NLRP1, and thereby suppresses a wide range of inflammatory stimuli.</p> Full article ">
25 pages, 5679 KiB  
Article
Malvidin-3-O-Glucoside Mitigates α-Syn and MPTP Co-Induced Oxidative Stress and Apoptosis in Human Microglial HMC3 Cells
by Rachit Sood, Sanjay, Sung-Ung Kang, Na Young Yoon and Hae-Jeung Lee
Int. J. Mol. Sci. 2024, 25(23), 12733; https://doi.org/10.3390/ijms252312733 - 27 Nov 2024
Viewed by 971
Abstract
Parkinson’s disease (PD) is a widespread age-related neurodegenerative disorder characterized by the presence of an aggregated protein, α-synuclein (α-syn), which is encoded by the SNCA gene and localized to presynaptic terminals in a normal human brain. The α-syn aggregation is induced by the [...] Read more.
Parkinson’s disease (PD) is a widespread age-related neurodegenerative disorder characterized by the presence of an aggregated protein, α-synuclein (α-syn), which is encoded by the SNCA gene and localized to presynaptic terminals in a normal human brain. The α-syn aggregation is induced by the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mitochondrial neurotoxin and is therefore used to mimic PD-like pathology in various in vitro and in vivo models. However, in vitro PD-like pathology using α-syn and MPTP in human microglial cells has not yet been reported. Malvidin-3-O-glucoside (M3G) is a major anthocyanin primarily responsible for pigmentation in various fruits and beverages and has been reported to possess various bioactivities. However, the neuroprotective effects of M3G in humanized in vitro PD-like pathologies have not been reported. Therefore, individual and co-treatments of α-syn and MPTP in a human microglial (HMC3) cell line were used to establish a humanized PD-like pathology model in vitro. The individual treatments were significantly less cytotoxic when compared to the α-syn and MPTP co-treatment. This study examined the neuroprotective effects of M3G by treating HMC3 cells with α-syn (8 μg/mL) and MPTP (2 mM) individually or in a co-treatment in the presence or absence of M3G (50 μM). M3G demonstrated anti-apoptotic, anti-inflammatory, and antioxidative properties against the α-syn- and MPTP-generated humanized in vitro PD-like pathology. This study determined that the cytoprotective effects of M3G are mediated by nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase (HO)-1 signaling. Full article
(This article belongs to the Special Issue Programmed Cell Death and Oxidative Stress: 3rd Edition)
►▼ Show Figures

Figure 1

Figure 1
<p>α-syn- and MPTP-induced cytotoxicity in HMC3 cells. HMC3 cells treated with (<b>a</b>) different concentrations of α-syn (0.5, 1, 2, 4, and 8 μg/mL), (<b>b</b>) different concentrations of MPTP (0.25, 0.5, 1, and 2 mM), and (<b>c</b>) individual or co-treatment of MPTP (2 mM) in the presence of various concentrations of α-syn (0.5, 1, 2, 4, and 8 μg/mL) for 24 h. C, control; α-syn, α-synuclein; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Experiments were conducted in triplicate, and all the data are shown as the mean ± standard deviation (SD). * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, and **** <span class="html-italic">p</span> &lt; 0.0001.</p> Full article ">Figure 2
<p>M3G protects HMC3 cells from α-syn- and MPTP-induced cytotoxicity. HMC3 cells (<b>a</b>) treated with different concentrations of M3G (6.25, 12.5, 25, 50, and 100 μM) and (<b>b</b>) co-treated with α-syn (8 μg/mL) and MPTP (2 mM) in the presence or absence of various concentrations of M3G (6.25, 12.5, 25, 50, and 100 μM). (<b>c</b>–<b>f</b>) HMC3 cells co-treated with α-syn (8 μg/mL) and MPTP (2 mM) in the presence or absence of M3G (50 μM). C, control; α-syn, α-synuclein; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; M3G, malvidin-3-O-glucoside. Experiments were conducted in triplicate, and all the data are shown as the mean ± standard deviation (SD). *** <span class="html-italic">p</span> &lt; 0.001 and **** <span class="html-italic">p</span> &lt; 0.0001.</p> Full article ">Figure 3
<p>M3G ameliorates α-syn- and MPTP-induced apoptosis by upregulating the transcriptional expression level of the anti-apoptotic marker and downregulating the pro-apoptotic markers in HMC3 cells. HMC3 cells were co-treated with α-syn (8 μg/mL) and MPTP (2 mM) in the presence or absence of M3G (50 μM), and the mRNA expression levels of (<b>a</b>) Bax, (<b>b</b>) Bcl2, (<b>c</b>) Casp-3, and (<b>d</b>) Casp-8 were analyzed by RT-PCR. α-syn, α-synuclein; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; M3G, malvidin-3-O-glucoside; Bax, Bcl-2-Associated X-protein; Bcl2, B-cell lymphoma 2; Casp, caspase. Experiments were conducted in triplicate, and all the data are shown as the mean ± standard deviation (SD). ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, and **** <span class="html-italic">p</span> &lt; 0.0001.</p> Full article ">Figure 4
<p>M3G ameliorates α-syn- and MPTP-induced apoptosis by upregulating the translational expression level of the anti-apoptotic marker and downregulating the pro-apoptotic markers in HMC3 cells. HMC3 cells were co-treated with α-syn (8 μg/mL) and MPTP (2 mM) in the presence or absence of M3G (50 μM). The protein expression level of (<b>a</b>) Bax, (<b>b</b>) Bcl2, (<b>c</b>) cleaved casp-3/pro-casp-3, and (<b>d</b>) casp-8 were analyzed by Western blot. α-syn, α-synuclein; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; M3G, malvidin-3-O-glucoside; Bax, Bcl-2-Associated X-protein; Bcl2, B-cell lymphoma 2; Casp, caspase. Experiments were conducted in triplicate, and all the data are shown as the mean ± standard deviation (SD). * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, and **** <span class="html-italic">p</span> &lt; 0.0001.</p> Full article ">Figure 5
<p>M3G downregulates α-syn- and MPTP-induced pro-inflammatory cytokines and upregulates the anti-inflammatory cytokine expressions in HMC3 cells. HMC3 cells were treated with α-syn (8 μg/mL) and MPTP (2 mM) individually or co-treated with α-syn (8 μg/mL) and MPTP (2 mM) in the presence or absence of M3G (50 μM) for 24 h, and the mRNA expression of the pro-inflammatory cytokines (<b>a</b>) IL-1β, (<b>b</b>) IL-6, and (<b>c</b>) TNF-α and the anti-inflammatory cytokines (<b>d</b>) IL-4 and (<b>e</b>) TGF-β was analyzed by RT-PCR. α-syn, α-synuclein; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; M3G, malvidin-3-O-glucoside; IL, interleukin; TNF-α, tumor necrosis factor-alpha; TGF-β, transforming growth factor-beta. Experiments were conducted in triplicate, and all the data are shown as the mean ± standard deviation (SD). * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, and **** <span class="html-italic">p</span> &lt; 0.0001.</p> Full article ">Figure 6
<p>M3G attenuates α-syn- and MPTP-induced reactive oxygen species (ROS) production. HMC3 cells were individually or co-treated with α-syn (8 μg/mL) and MPTP (2 mM) in the presence or absence of M3G (50 μM). Intracellular ROS levels were determined using the DCFH-DA assay through (<b>a</b>) a microplate reader and (<b>b</b>) fluorescence microscopy. α-syn, α-synuclein; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; M3G, malvidin-3-O-glucoside; ROS, reactive oxygen species. * <span class="html-italic">p</span> &lt; 0.05 and **** <span class="html-italic">p</span> &lt; 0.0001.</p> Full article ">Figure 7
<p>M3G ameliorates the oxidative stress by upregulating the transcriptional expression levels of antioxidants in α-syn- and MPTP-induced HMC3 cells. HMC3 cells were individually or co-treated with α-syn (8 μg/mL) and MPTP (2 mM) in the presence or absence of M3G (50 μM). The relative mRNA expression levels of the antioxidants (<b>a</b>) Nrf2, (<b>b</b>) HO-1, (<b>c</b>) CAT, (<b>d</b>) SOD, (<b>e</b>) HO-2, and (<b>f</b>) GPx were analyzed using RT-PCR. α-syn, α-synuclein; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; M3G, malvidin-3-O-glucoside; Nrf2, nuclear factor erythroid 2-related factor 2; HO-1/2, heme oxygenase 1/2; CAT, catalase; SOD, superoxide dismutase; GPx, glutathione peroxidase. Experiments were conducted in triplicate, and all the data are shown as the mean ± standard deviation (SD). * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, and **** <span class="html-italic">p</span> &lt; 0.0001.</p> Full article ">Figure 8
<p>M3G ameliorates oxidative stress by upregulating the translational expression levels of antioxidants in α-syn- and MPTP-induced HMC3 cells. HMC3 cells were individually or co-treated with α-syn (8 μg/mL) and MPTP (2 mM) in the presence or absence of M3G (50 μM). The relative protein expression levels of the antioxidants (<b>a</b>) Nrf2, (<b>b</b>) Keap1, (<b>c</b>) HO-1, (<b>d</b>) CAT, (<b>e</b>) SOD, (<b>f</b>) HO-2, and (<b>g</b>) GPx were analyzed using Western blotting. α-syn, α-synuclein; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; M3G, malvidin-3-O-glucoside; Nrf2, nuclear factor erythroid 2-related factor 2; Keap1, Kelch-like ECH-associated protein 1; HO-1/2, heme oxygenase 1/2; CAT, catalase; SOD, superoxide dismutase; GPx, glutathione peroxidase. Experiments were conducted in triplicate, and all the data are shown as the mean ± standard deviation (SD). * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, and **** <span class="html-italic">p</span> &lt; 0.0001.</p> Full article ">Figure 9
<p>M3G mediates antioxidative effects through Nrf2/HO-1 signaling. HMC3 cells were individually or co-treated with α-syn (8 μg/mL) and MPTP (2 mM) in the presence or absence of M3G (50 μM), with or without ML385 (5 μM). Intracellular ROS levels in α-syn- and MPTP-induced HMC3 cells were determined using the DCFH-DA assay through (<b>a</b>) a microplate reader and (<b>b</b>) fluorescence microscopy. α-syn, α-synuclein; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; M3G, malvidin-3-O-glucoside; ROS, reactive oxygen species. **** <span class="html-italic">p</span> &lt; 0.0001.</p> Full article ">Figure 10
<p>M3G mediates anti-apoptotic effects through Nrf2/HO-1 signaling. (<b>a</b>–<b>e</b>) HMC3 cells were co-treated with α-syn (8 μg/mL) and MPTP (2 mM) in presence or absence of M3G (50 μM), with/without ML385 (5 μM), and were analyzed for the relative cell count of apoptotic cells using the annexin V–FITC apoptosis assay kit. α-syn, α-synuclein; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; M3G, malvidin-3-O-glucoside. Experiments were conducted in triplicate, and all the data are shown as the mean ± standard deviation (SD). **** <span class="html-italic">p</span> &lt; 0.0001.</p> Full article ">Scheme 1
<p>Malvidin-3-O-glucoside ameliorates α-syn and MPTP co-induced cytotoxicity in HMC3 cell model of Parkinson’s disease. PD, Parkinson’s disease; HMC3, human microglial cells; α-syn, α-synuclein; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; M3G, malvidin-3-O-glucoside; IL, interleukin; TNF-α, tumor necrosis factor-alpha; TGF-β, transforming growth factor-beta; ROS, reactive oxygen species; SOD, superoxide dismutase; CAT, catalase; Nrf2, nuclear factor erythroid 2-related factor 2; HO-1/2, heme oxygenase 1/2; GPx, glutathione peroxidase; Keap1, Kelch-like ECH-associated protein 1; ARE, antioxidant responsive element; Bax, Bcl-2-Associated X-protein; Bcl2, B-cell lymphoma 2; Casp, caspase; ↑, upregulation; ↓, downregulation.</p> Full article ">
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-2
Back to TopTop