Leptin mediates protection of hydrogen sulfide against 6-hydroxydopamine-induced Parkinson's disease: Involving enhancement in Warburg effect
Abstract
Background Hydrogen sulfide (H 2 S) has therapeutic effects on Parkinson's disease (PD). Warburg effect, namely aerobic glycolysis, is benefit to PD. Leptin, a hormone secreted in adipose, plays an important role in the treatment of PD.Objective To determine whether the mechanism underlying protection of H 2 S against PD is involved in promoting Warburg effect via upregulation of leptin.Methods We set a PD model via unilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA) in Sprague Dawley rat. PD-like behavior was analyzed by apomorphine-induced rotations, open field activity test, stepping test and cylinder test. Dopaminergic neurons were detected by immunohistochemistry. The expressions of Hexokinase-2, pyruvate kinase M-2, lactate dehydrogenase, pyruvate dehydrogenase kinase, pyruvate dehydrogenase, and leptin were measured by Western blot. Lactate dehydrogenase (LDHA) activity was monitored by ELISA. The lactate content was measured by lactate assay kit.Results We showed that NaHS (a donor of H 2 S) prevented 6-OHDA-induced PD-like behaviors as well as the loss of dopaminergic neurons. We also found that NaHS enhanced the Warburg effect and upregulated leptin expression in the substantia nigra of 6-OHDA-exposed rats. While, inhibited leptin signaling by OBR13-A reversed the protections of H 2 S against 6-OHDA-exerted PD-like behaviors and the loss of dopaminergic neurons in the substantia nigra, and abolished H 2 S-enhanced in the Warburg effect in the substantia nigra.Conclusion These data indicated that leptin mediates the protection of H 2 S against PD, which involves enhancing the Warburg effect of the substantia nigra.
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Leptin signaling has an important role in preserving the dopaminergic system.
“leptin signaling also has an important role in preserving the dopaminergic system.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [591]
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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193 · see citing works
- Authors
- Yang, S.-Q., Tian, Q., Li, D., He, S.-Q., Hu, M., Liu, S.-Y., Zou, W., Chen, Y.-J., Zhang, P., & Tang, X.-Q.
- Affiliations
- First Affiliated Hospital of University of South China (CN)
- University of South China (CN)
- Guangdong Medical College (CN)
- Corresponding author
- Tang, Xiao-Qing
- Venue
- Neurochemistry International
- Publisher
- Elsevier BV
- Published
- 2020-05
- Volume
- 135
- Pages
- 104692
- ISSN
- 0197-0186 (ISSN-L)
- OpenAlex
- W3005182452
- Cited by
- 25
- References
- 51
- Citations by year
- 2025: 4 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 6 · 2020: 4
- FWCI
- 1.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurochemistry International (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Natural Science Foundation of Guangdong Province
- National Natural Science Foundation of China
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- hydrogen sulfide, leptin, Parkinson's disease, Warburg effect, aerobic glycolysis, 6-hydroxydopamine, dopaminergic neurons, substantia nigra, hexokinase 2, lactate dehydrogenase, sodium hydrosulfide, neuroprotection
- MeSH terms
- Warburg Effect, Oncologic, Animals, Dose-Response Relationship, Drug, Hydrogen Sulfide, Male, Random Allocation, Oxidopamine, Rats, Sprague-Dawley, Neuroprotective Agents, Parkinsonian Disorders, Leptin, Rats
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