Changes in opioid receptor proteins during mitochondrial impairment in differentiated SK-N-SH cells.
Aging and neurodegenerative diseases are associated with oxidative damage that may contribute to changes in neurosensory processing, including pain. The effects of neuronal oxidation on the opioid receptor system are poorly understood. Earlier, we have reported that 3-nitroproprionic acid (3-NPA)-induced oxidative stress and impairment of mitochondrial energy metabolism significantly reduced the function of mu but not delta opioid receptors [A. Raut, M. Iglewski, A. Ratka, Differential effects of impaired mitochondrial energy production on the function of mu and delta opioid receptors in neuronal SK-N-SH cells, Neurosci. Lett. 404 (2006) 242-246]. In the present study, we studied the effects of 3-NPA-induced oxidative stress on protein levels of the mu, delta, and kappa opioid receptors (MOR, DOR, and KOR, respectively). The opioid-responsive differentiated SK-N-SH neuronal cells were used as an in vitro model. Cells were exposed to 0, 5, 10, and 20mM of 3-NPA for 0, 1, 2, 12, and 24h. After the 3-NPA treatments, plasma membrane preparations were made and used for the Western blot assay. There was a significant reduction in the level of the MOR protein while levels of DOR and KOR proteins remained unaffected after exposure to 3-NPA. These findings demonstrate for the first time that there is a selective impairment of the MOR protein under conditions of mitochondrial oxidative damage at the neuronal level. The reduction in the level of the MOR protein may contribute to the impairment of MOR function under oxidative damage conditions shown in our previous study.
Raut
Atul
A
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, TX 76107, USA.
Rao
Vidhya R
VR
Ratka
Anna
A
D000927:Anticonvulsants / Q000633:toxicity; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology*; D009574:Nitro Compounds / Q000633:toxicity; D018384:Oxidative Stress / Q000502:physiology*; D011422:Propionates / Q000633:toxicity; D011957:Receptors, Opioid / Q000096:biosynthesis* / Q000187:drug effects
D000927:Anticonvulsants; D009574:Nitro Compounds; D011422:Propionates; D011957:Receptors, Opioid; C015392:3-nitropropionic acid