Neoechinulin a impedes the progression of rotenone-induced cytotoxicity in PC12 cells.

Abstract

Neoechinulin A, an indole alkaloid from marine fungi, can protect PC12 cells from the cytotoxicity of 1-methyl-4-phenylpyridinium (MPP(+)), a Parkinson disease-inducing neurotoxin, by ameliorating downstream events resulting from mitochondrial complex I inactivation. However, the cytoprotective mechanisms remained unclear. In this study, by using rotenone, another parkinsonian-inducing neurotoxin targeting mitochondrial complex I, we investigated the cytoprotective mechanism of neoechinulin A. Rotenone-induced cell death was associated with accelerated glucose consumption, and excess glucose supplementation in the culture medium almost completely suppressed cell death, suggesting that glucose deficiency in the medium is critical for triggering cell death in this model. Co-treatment with neoechinulin A, but not neoechinulin A pre-treatment before rotenone exposure, significantly impeded cell death by rotenone. Although the presence of neoechinulin A did not affect the accelerated glycolytic turnover in rotenone-treated cells, it paradoxically decreased ATP levels in the cells, suggesting increased ATP consumption. Although the link between the decreased ATP levels and cytoprotection is not clear at present, it suggests that neoechinulin A may ameliorate rotenone toxicity by activating a cytoprotective machinery that requires ATP.

• Authors: Soichiro Akashi, Tomonori Kimura, Toshifumi Takeuchi, Kouji Kuramochi, Susumu Kobayashi, Fumio Sugawara, Nobuo Watanabe, Takao Arai
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 34 Issue 2 Pg. 243-8 ( 2011) ISSN: 1347-5215 [Electronic] Japan
• PMID: 21415535 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkaloids
• Biological Products
• Insecticides
• Piperazines
• Rotenone
• neoechinulin
• Adenosine Triphosphate
• Electron Transport Complex I
• Glucose
• 1-Methyl-4-phenylpyridinium

Topics

• 1-Methyl-4-phenylpyridinium
• Adenosine Triphosphate (metabolism)
• Alkaloids (administration & dosage, pharmacology, therapeutic use)
• Animals
• Biological Products (administration & dosage, pharmacology, therapeutic use)
• Cell Death (drug effects, physiology)
• Cytoprotection
• Electron Transport Complex I (metabolism)
• Fungi (chemistry)
• Glucose (metabolism, pharmacology)
• Insecticides (toxicity)
• Mitochondria (drug effects, metabolism)
• PC12 Cells
• Parkinson Disease (drug therapy, metabolism)
• Piperazines (administration & dosage, pharmacology, therapeutic use)
• Rats
• Rotenone (toxicity)