Rotenone induces KATP channel opening in PC12 cells in association with the expression of tyrosine hydroxylase

Bai,Qunhua; He,Junlin; Qiu,Jingfu; Wang,Yang; Wang,Shibo; Xiu,Yun; Yu,Chao

doi:10.3892/or.2012.1959

Rotenone induces KATP channel opening in PC12 cells in association with the expression of tyrosine hydroxylase

Authors:
- Qunhua Bai
- Junlin He
- Jingfu Qiu
- Yang Wang
- Shibo Wang
- Yun Xiu
- Chao Yu
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Affiliations: Institute of Life Science, Chongqing Medical University, Chongqing 400016, P.R. China, School of Public Health, Chongqing Medical University, Chongqing 400016, P.R. China
Published online on: August 8, 2012 https://doi.org/10.3892/or.2012.1959
Pages: 1376-1384

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Abstract

The activation of ATP-sensitive potassium (KATP) channels in PC12 cells play a pivotal role in protection against the neurotoxic effect of rotenone. However, it remains unclear why rotenone seems to preferentially affect activation of KATP channels and if this could affect its physiological activity. In this study, we sought to determine how the different energy states caused by various doses of rotenone affect the KATP opening state and whether the KATP opening state influences the expression of tyrosine hydroxylase (TH) which is related with DA synthesis. With patch clamp technology, results showed that treatment of PC12 cells with rotenone (0.2-1 µg/ml) for 15 min can cause KATP channel opening with significantly increased intracellular ROS production. Treatment with rotenone (2-16 ng/ml) for 24 h also caused the channels to open with gently increased ROS. In order to study if the rather long-term action on KATP channel opening states could affect the specified function of PC12 cells, the KATP channel opener pinacidil and the inhibitor glibenclamide were used to treat cells for 24 h, and the expression of TH was detected. Our results showed that treatment of PC12 cells with glibenclamide for 24 h can notably promote TH expression and can also enhance the expression of TH which were reduced by rotenone. These data indicate that the energy states in PC12 induced by various doses of rotenone could significantly influence the opening states of KATP channels. However long-term energy stress may raise the opening rate and opening sensitivity of this channel. In addition, our results demonstrate for the first time that activation of plasma membrane KATP channels induced by rotenone inhibits TH expression which influences DA synthesis in PC12 cells.

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1	Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV and Greenamyre JT: Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci. 3:1301–1306. 2000.
2	Dawson TM and Dawson VL: Molecular pathways of neurodegeneration in Parkinson’s disease. Science. 302:819–822. 2003.
3	Di Monte DA: The environment and Parkinson’s disease: is the nigrostriatal system preferentially targeted by neurotoxins? Lancet Neurol. 2:531–538. 2003.
4	Hartley A, Stone JM, Heron C, Cooper JM and Schapira AH: Complex I inhibitors induce dose-dependent apoptosis in PC12 cells: relevance to Parkinson’s disease. J Neurochem. 63:1987–1990. 1994.PubMed/NCBI
5	Pitkanen S and Robinson BH: Mitochondrial complex I deficiency leads to increased production of superoxide radicals and induction of superoxide dismutase. J Clin Invest. 98:345–351. 1996. View Article : Google Scholar : PubMed/NCBI
6	Votyakova TV and Reynolds IJ: ΔΨm-dependent and -independent production of reactive oxygen species by rat brain mitochondria. J Neurochem. 79:266–277. 2001.
7	Liss B, Haeckel O, Wildmann J, Miki T, Seino S and Roeper J: K-ATP channels promote the differential degeneration of dopaminergic midbrain neurons. Nat Neurosci. 8:1742–1751. 2005. View Article : Google Scholar : PubMed/NCBI
8	Javoy-Agid F, Hirsch EC, Dumas S, Duyckaerts C, Mallet J and Agid Y: Decreased tyrosine hydroxylase messenger RNA in the surviving dopamine neurons of the substantia nigra in parkinson’s disease: an in situ hybridization study. Neuroscience. 38:245–253. 1990.
9	Mosmann T: Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 65:55–63. 1983. View Article : Google Scholar : PubMed/NCBI
10	Wu C, Yang K, Liu Q, Wakui M, Jin GZ, Zhen XC and Wu J: Tetrahydroberberine blocks ATP-sensitive potassium channels in dopamine neurons acutely-dissociated from rat substantia nigra pars compacta. Neuropharmacology. 59:567–572. 2010. View Article : Google Scholar : PubMed/NCBI
11	Koshimura K, Tanaka J, Murakami Y and Kato Y: Effect of high concentration of glucose on dopamine release from pheochromocytoma-12 cells. Metabolism. 52:922–926. 2003. View Article : Google Scholar : PubMed/NCBI
12	Tai KK, McCrossan ZA and Abbott GW: Activation of mitochondrial ATP-sensitive potassium channels increases cell viability against rotenone-induced cell death. J Neurochem. 84:1193–1200. 2003. View Article : Google Scholar : PubMed/NCBI
13	Lamensdorf I, He LP, Nechushtan A, Harvey-White J, Eisenhofer G, Milan R, Rojas E and Kopin IJ: Effect of glipizide on dopamine synthesis, release and metabolism in PC12 cells. Eur J Pharmacol. 388:147–154. 2000. View Article : Google Scholar : PubMed/NCBI
14	Liss B and Roeper J: ATP-sensitive potassium channels in dopaminergic neurons: transducers of mitochondrial dysfunction. News Physiol Sci. 16:214–217. 2001.PubMed/NCBI
15	Zingman LV, Hodgson DM, Bast PH, Kane GC, Perez-Terzic C, Gumina RJ, Pucar D, Bienengraeber M, Dzeja PP, Miki T, et al: Kir6.2 is required for adaptation to stress. Proc Natl Acad Sci USA. 99:13278–13283. 2002. View Article : Google Scholar : PubMed/NCBI
16	Olson TM and Terzic A: Human K_ATP channelopathies: diseases of metabolic homeostasis. Pflugers Arch. 460:295–306. 2010.PubMed/NCBI
17	Van den Top M, Lyons DJ, Lee K, Coderre E, Renaud LP and Spanswick D: Pharmacological and molecular characterization of ATP-sensitive K⁺ conductances in CART and NPY/AgRP expressing neurons of the hypothalamic arcuate nucleus. Neuroscience. 144:815–824. 2007.PubMed/NCBI
18	Sherer TB, Betarbet R, Testa CM, Seo BB, Richardson JR, Kim JH, Miller GW, Yagi T, Matsuno-Yagi A and Greenamyre JT: Mechanism of toxicity in rotenone models of Parkinson’s disease. J Neurosci. 23:10756–10764. 2003.
19	Tai KK and Truong DD: Activation of ATP-sensitive potassium channel confers protection against rotenone-induced cell death: therapeutic implications for Parkinson’s disease. J Neurosci Res. 69:559–566. 2002.PubMed/NCBI
20	Saravanan KS, Sindhu KM and Mohanakumar KP: Acute intranigral infusion of rotenone in rats causes progressive biochemical lesions in the striatum similar to Parkinson’s disease. Brain Res. 1049:147–155. 2005.PubMed/NCBI
21	Liu YM, Jiang B, Bao YM and An LJ: Protocatechuic acid inhibits apoptosis by mitochondrial dysfunction in rotenone-induced PC12 cells. Toxicol In Vitro. 22:430–437. 2008. View Article : Google Scholar : PubMed/NCBI
22	Islam MS, Berggren PO and Larsson O: Sulfhydryl oxidation induces rapid and reversible closure of the ATP-regulated K⁺ channel in the pancreatic β-cell. FEBS Lett. 319:128–132. 1993. View Article : Google Scholar : PubMed/NCBI
23	Alekseev AE, Hodgson DM, Karger AB, Park S, Zingman LV and Terzic A: ATP-sensitive K⁺ channel channel/enzyme multimer: metabolic gating in the heart. J Mol Cell Cardiol. 38:895–905. 2005.
24	Kastner A, Hirsch E, Agid Y and Javoy-Agid F: Tyrosine hydroxylase protein and messenger RNA in the dopaminergic nigral neurons of patients with Parkinson’s disease. Brain Res. 606:341–345. 1993.PubMed/NCBI
25	Lee TM, Lin MS and Chang NC: Effect of pravastatin on sympathetic reinnervation in postinfarcted rats. Am J Physiol Heart Circ Physiol. 293:H3617–H3626. 2007. View Article : Google Scholar : PubMed/NCBI
26	He XB, Yi SH, Rhee YH, Kim H, Han YM, Lee SH, Lee H, Park CH, Lee YS, Richardson E, et al: Prolonged membrane depolarization enhances midbrain dopamine neuron differentiation via epigenetic histone modifications. Stem Cells. 29:1861–1873. 2011. View Article : Google Scholar
27	Kilbourne EJ, McMahon A and Sabban EL: Membrane depolarization by isotonic or hypertonic KCl: differential effects on mRNA levels of tyrosine hydroxylase and dopamine β-hydroxylase mRNA in PC12 cells. J Neurosci Methods. 40:193–202. 1991.