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.
Graphical abstract
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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
04 April 2024
A Correction to this paper has been published: https://doi.org/10.1007/s43440-024-00591-8
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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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.
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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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DOI: https://doi.org/10.1007/s43440-024-00572-x