Leptin mediates protection of hydrogen sulfide against 6-hydroxydopamine-induced Parkinson's disease: Involving enhancement in Warburg effect

• Published in: Neurochemistry international Vol. 135; p. 104692
• Main Authors: Yang, San-Qiao, Tian, Qing, Li, Dan, He, Shi-Qing, Hu, Min, Liu, Shu-Yun, Zou, Wei, Chen, Yong-Jun, Zhang, Ping, Tang, Xiao-Qing
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2020
• Subjects: 6-Hydroxydopamine; Animals; Dose-Response Relationship, Drug; Hydrogen sulfide; Hydrogen Sulfide - pharmacology; Hydrogen Sulfide - therapeutic use; Leptin; Leptin - metabolism; Male; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Oxidopamine - toxicity; Parkinson disease; Parkinsonian Disorders - chemically induced; Parkinsonian Disorders - metabolism; Parkinsonian Disorders - prevention & control; Random Allocation; Rats; Rats, Sprague-Dawley; Warburg effect; Warburg Effect, Oncologic - drug effects; 6-Hydroxydopamine; Parkinson disease; H2S; 6-OHDA; HK-2; PFA; Hydrogen sulfide; LDHA; PD; PDH; Leptin; PDK-1; PKM-2; Warburg effect
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2020.104692

Hydrogen sulfide (H2S) 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. To determine whether the mechanism underlying protection of H2S against PD is involved in promoting Warburg effect via upregulation of leptin. 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. We showed that NaHS (a donor of H2S) 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 H2S against 6-OHDA-exerted PD-like behaviors and the loss of dopaminergic neurons in the substantia nigra, and abolished H2S-enhanced in the Warburg effect in the substantia nigra. Conclusion: These data indicated that leptin mediates the protection of H2S against PD, which involves enhancing the Warburg effect of the substantia nigra. •H2S attenuates dopaminergic neurons loss and enhances Warburg effect in the substantial nigra of PD rats.•H2S increases leptin expression in the substantial nigra of PD rats.•Inhibited leptin signaling pathway reverses H2S-blocked PD-like behaviors.•Inhibited leptin signaling pathway reverses H2S-reduced dopaminergic neurons loss.•Inhibited leptin signaling pathway reverses H2S-enhanced Warburg effect.