Effect of dopaminergic neurotoxin MPTP/MPP + on coenzyme Q content Muralikrishnan Dhanasekaran a, ⁎, Senthilkumar S. Karuppagounder a , Subramaniam Uthayathas a , Loren E. Wold b , Kodeeswaran Parameshwaran a , R. Jayachandra Babu a , Vishnu Suppiramaniam a , Holly Brown-Borg c a Division of Pharmacology and Toxicology, Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA b Center for Cardiovascular and Pulmonary Research, The Research Institute at Nationwide Children's Hospital and Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, 43205, USA c Department of Pharmacology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58201, USA ABSTRACT ARTICLE INFO Article history: Received 7 December 2007 Accepted 22 April 2008 Keywords: Coenzyme Q MPTP Oxidative stress Parkinson's disease Coenzyme Q10, an endogenous lipophilic antioxidant, plays an indispensable role in ATP synthesis. The therapeutic value of coenzyme Q10 in Parkinson's disease and other neurodegenerative disorders is still being tested and the preliminary results are promising. The 1-methyl-4-phenyl-1, 2, 3, 6 tetrahydropyridine (MPTP)-treated mouse is a valid and accepted animal model for Parkinson's disease. 1-methyl-4- phenylpyridinium (MPP + ) is an active toxic metabolite of MPTP. MPP + and MPTP are known to induce oxidative stress and mitochondrial dysfunction. However, the effect of MPP + and MPTP on coenzyme Q is not clearly understood. The present study investigated the in vitro and in vivo effect of MPP + and MPTP on coenzyme Q content. Coenzyme Q content was measured using HPLC–UV detection methods. In the in vitro studies, MPP + (0-50 μM) was incubated with SH-SY5Y human neuroblastoma cells and NG-108-15 (mouse/ rat, neuroblastoma × glioma hybrid) cells. MPP + concentration dependently increased coenzyme Q10 content in SH-SY5Y cells. In NG-108-15 cells, MPP + concentration dependently increased both coenzyme Q9 and Q10 content. In the in vivo study, mice were administered with MPTP (30 mg/kg, twice 16 h apart) and sacrificed one week after the last administration. Administration of MPTP to mice significantly increased coenzyme Q9 and coenzyme Q10 levels in the nigrostriatal tract. However, MPTP did not affect the coenzyme Q content in the cerebellum, cortex and pons. This study demonstrated that MPP + /MPTP significantly affected the coenzyme Q content in the SH-SY5Y and NG-108 cells and in the mouse nigrostriatal tract. © 2008 Elsevier Inc. All rights reserved. Introduction Coenzyme Q (ubiquinone) is an endogenous lipophilic antioxidant compound biosynthesized in most living cells (Beal, 2004; Beyer, 1990; Crane, 2001; Ebadi et al., 2000; Ebadi et al., 2001). It is ubiquitous in nature and widely distributed in animals, plants, and microorganisms (Albano et al,. 2002; Crane, 2001; Ebadi et al., 2000; Ebadi et al., 2001). Coenzyme Q is present in subcellular organelles, serum lipoproteins, blood plasma, urine, feces, plasma membrane and endomembranes (Kawamukai, 2002; Takahashi et al., 1993). Coenzyme Q's are amphi- pathic representing that it has both hydrophilic (benzoquinone ring) and the lipophilic (polyisoprenoid side chain moiety) groups. The coen- zymes Q n (n =0–12) differ from each other slightly in chemical structure with regard to the isoprenoid side chain which is attached to the benzoquinone ring (Albano et al., 2002; Crane, 2001). Coenzyme Q9 is found higher levels in the brains of rodents whereas not detectable in the brains of chickens and rabbits, and also in human cell lines (Albano et al., 2002). Coenzyme Q10 is the highest occurring coenzyme Q in humans and is an essential component in the translocation of protons and electrons in the mitochondrial electron transfer chain to generate ATP (Ebadi et al., 2000; Kagen et al., 1999). It is an important bioenergetic component in the living system due to its involvement in mitochondrial respiration and in cytoprotective mechanisms such as inhibition of apoptosis and reduction of generation of free radicals (Crane, 2001; Ebadi et al., 2000; Ebadi et al., 2001; Horvath et al., 2003; Kagen et al., 1999; Lagendijk et al., 1996; Papucci et al., 2003). Parkinson's disease is a degenerative neurological disorder char- acterized by degeneration of dopaminergic neurons in the substantia nigra. Oxidative stress and mitochondrial dysfunction play significant roles in the pathogenesis of this dopaminergic disorder (Beal, 2004; Ebadi et al., 2001). Platelets of mitochondria from parkinsonian pa- tients were found to have altered levels of coenzyme Q10 as compared to their age/sex-matched controls (Gotz et al., 2000; Isobe et al., 2007; Sohmiya et al., 2004). An age-related decline of coenzyme Q10 occurs in humans and animals (Lagendijk et al., 1996; Lenaz et al., 1999; Lonnrot et al., 1995). Oral administration of coenzyme Q10 in monkeys induces nigral mitochondrial uncoupling and protects dopaminergic Life Sciences 83 (2008) 92–95 ⁎ Corresponding author. Tel.: +1 334 844 8327; fax: +1 334 844 8331. E-mail address: dhanamu@auburn.edu (M. Dhanasekaran). 0024-3205/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.lfs.2008.04.016 Contents lists available at ScienceDirect Life Sciences journal homepage: www.elsevier.com/locate/lifescie