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Protective effect of hygrolansamycin C against corticosterone-induced toxicity and oxidative stress-mediated via autophagy and the MAPK signaling pathway

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A Correction to this article was published on 04 April 2024

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Abstract

Background

Excessive stress, a major problem in modern societies, affects people of all ages worldwide. Corticosterone is one of the most abundant hormones secreted during stressful conditions and is associated with various dysfunctions in the body. In particular, we aimed to investigate the protective effects of hygrolansamycin C (HYGC) against corticosterone-induced cellular stress, a manifestation of excessive stress prevalent in contemporary societies.

Methods

We isolated HYGC from Streptomyces sp. KCB17JA11 and subjected PC12 cells to corticosterone-induced stress. The effects of HYGC were assessed by measuring autophagy and the expression of mitogen-activated protein kinase (MAPK) phosphorylation-related genes. We used established cellular and molecular techniques to analyze protein levels and pathways.

Results

HYGC effectively protected cells against corticosterone-induced injury. Specifically, it significantly reduced corticosterone-induced oxidative stress and inhibited the expression of autophagy-related proteins induced by corticosterone, which provided mechanistic insight into the protective effects of HYGC. At the signaling level, HYGC suppressed c-Jun N-terminal kinase and extracellular signal-regulated kinase phosphorylation and p38 activation.

Conclusions

HYGC is a promising candidate to counteract corticosterone-induced apoptosis and oxidative stress. Autophagy and MAPK pathway inhibition contribute to the protective effects of HYGC. Our findings highlight the potential of HYGC as a therapeutic agent for stress-related disorders and serve as a stepping stone for further exploration and development of stress management strategies.

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Data availability

The datasets generated and/or analyzed in this study are available from the corresponding author upon reasonable request.

Change history

Abbreviations

AA:

Ascorbic acid

HYGC:

Hygrolansamycin C

HYGs:

Hygrolansamycins

CORT:

Corticosterone

LC3:

Light chain 3

PI:

Propidium iodide

MAPK:

Mitogen-activated protein kinase

DMEM:

Dulbecco's modified Eagle's medium

FBS:

Fetal bovine serum

ERK:

Extracellular signal regulated kinase

JNK:

C-Jun N-terminal kinase

DPPH:

1,1-diphenyl-2-picryl-hydrazyl

ROS:

Reactive oxygen species

GSH:

Glutathione

DCFH-DA:

20,70-dichlorodihydrofluorescein diacetate

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Funding

This work was supported by a grant from the National Research Foundation of Korea (NRF) (2017R1C1B2002602 [S.-K.K.]), the National Research Council of Science & Technology (NST) (CAP23011-300 [Y.-S.H.]), and Korea Research Institute of Bioscience and Biotechnology Research Initiative Program (KGM5292423 and KGM1222413) funded by the Ministry of Science ICT (MSIT) of the Republic of Korea.

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Authors and Affiliations

Authors

Contributions

Jongtae Roh: Conceptualization, Data curation, Formal analysis, Writing – original draft. Jun-Pil Jang: Formal analysis, Resource provision. Taehoon Oh: Data curation, Formal analysis. Jihong Kim: Data curation, Formal analysis. Byeongsan Lee: Data curation, Formal analysis. Young-Soo Hong: Data curation, Formal analysis. Jae-Hyuk Jang: Data curation, Formal analysis, Resource provision, Funding acquisition. Sung-Kyun Ko: Conceptualization, Data curation, Formal analysis, Writing – review & editing, Project administration, and Supervision.

Corresponding authors

Correspondence to Jae-Hyuk Jang or Sung-Kyun Ko.

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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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The original online version of this article was revised: In this article "μ" symbol was missing from the "μM" notation for substance concentration in Figures 2 and 4. Additionally, the symbol "β" in "β-Actin" is missing in Figures 5-7.

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Roh, J., Jang, JP., Oh, T. et al. Protective effect of hygrolansamycin C against corticosterone-induced toxicity and oxidative stress-mediated via autophagy and the MAPK signaling pathway. Pharmacol. Rep 76, 368–378 (2024). https://doi.org/10.1007/s43440-024-00572-x

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