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Int. J. Mol. Sci. 2017, 18(5), 1096; doi:10.3390/ijms18051096

The 1-Tosylpentan-3-one Protects against 6-Hydroxydopamine-Induced Neurotoxicity

1,2,3,†
,
1,4,†
,
1
,
1,5,6
,
1,5,6
,
1
,
7,8
,
9,10,11,12
,
3
,
13,14,* and 1,5,*
1
Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 804, Taiwan
2
Department of Internal Medicine, Gangshan Branch of Armed Forces Kaohsiung General Hospital, No. 1, Dayi 2nd Rd., Gangshan Dist., Kaohsiung City 820, Taiwan
3
National Defense Medical Center, Department of Internal Medicine of Gangshan Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung 82049, Taiwan
4
Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 804, Taiwan
5
Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University, 70 Lien-Hai Road, Kaohsiung 804, Taiwan
6
Doctoral Degree Program in Marine Biotechnology, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan
7
Department of Anesthesiology, Taipei Veterans General Hospital, No. 201, Section 2, Shipai Road, Taipei 11217, Taiwan
8
School of Medicine, National Yang-Ming University, No. 155, Section 2, Linong Street, Taipei 11221, Taiwan
9
Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung 804, Taiwan
10
Department of Obstetrics and Gynecology and Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan
11
Department of Biological Science, National Sun Yat-sen University, Kaohsiung 804, Taiwan
12
Department of Pharmacy and Master Program, College of Pharmacy and Health Care, Tajen University, Pingtung 900, Taiwan
13
Division of Neurosurgery, Department of Surgery, Kaohsiung Armed Forces General Hospital, Kaohsiung 804, Taiwan
14
Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Katalin Prokai-Tatrai
Received: 5 April 2017 / Revised: 12 May 2017 / Accepted: 13 May 2017 / Published: 19 May 2017
(This article belongs to the Special Issue Neuroprotective Strategies 2017)
View Full-Text   |   Download PDF [4808 KB, uploaded 19 May 2017]   |  

Abstract

Previous studies have demonstrated that the marine compound austrasulfone, isolated from the soft coral Cladiella australis, exerts a neuroprotective effect. The intermediate product in the synthesis of austrasulfone, dihydroaustrasulfone alcohol, attenuates several inflammatory responses. The present study uses in vitro and in vivo methods to investigate the neuroprotective effect of dihydroaustrasulfone alcohol-modified 1-tosylpentan-3-one (1T3O). Results from in vitro experiments show that 1T3O effectively inhibits 6-hydroxydopamine-induced (6-OHDA-induced) activation of both p38 mitogen-activated protein kinase (MAPK) and caspase-3 in SH-SY5Y cells; and enhances nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression via phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling. Hoechst staining and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining results reveal that 1T3O significantly inhibits 6-OHDA-induced apoptosis. In addition, the addition of an Akt or HO-1 inhibitor decreases the protective effect of 1T3O. Thus, we hypothesize that the anti-apoptotic activity of 1T3O in neuronal cells is mediated through the regulation of the Akt and HO-1 signaling pathways. In vivo experiments show that 1T3O can reverse 6-OHDA-induced reduction in locomotor behavior ability in zebrafish larvae, and inhibit 6-OHDA-induced tumor necrosis factor-alpha (TNF-α) increase at the same time. According to our in vitro and in vivo results, we consider that 1T3O exerts its anti-apoptotic activities at SH-SY5Y cells after 6-OHDA challenges, probably via the regulation of anti-oxidative signaling pathways. Therefore, this compound may be a promising therapeutic agent for neurodegenerations. View Full-Text
Keywords: neuroprotection; 6-OHDA-induced apoptosis; marine compounds; zebrafish; SH-SY5Y cells; 1-tosylpentan-3-one neuroprotection; 6-OHDA-induced apoptosis; marine compounds; zebrafish; SH-SY5Y cells; 1-tosylpentan-3-one
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MDPI and ACS Style

Kao, C.-J.; Chen, W.-F.; Guo, B.-L.; Feng, C.-W.; Hung, H.-C.; Yang, W.-Y.; Sung, C.-S.; Tsui, K.-H.; Chu, H.; Chen, N.-F.; Wen, Z.-H. The 1-Tosylpentan-3-one Protects against 6-Hydroxydopamine-Induced Neurotoxicity. Int. J. Mol. Sci. 2017, 18, 1096.

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