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Real-Time Translocation and Function of PKCβII Isoform in Response to Nociceptive Signaling via the TRPV1 Pain Receptor
Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N4N1, Canada
Brain Mind Research Institute and the Nerve Research Foundation, University of Sydney, Sydney, NSW 2006, Australia
Faculty of Pharmacy, University of Sydney, Room 341, Pharmacy and Bank Building A15, Sydney, NSW 2006, Australia
* Authors to whom correspondence should be addressed.
Received: 12 October 2011; in revised form: 26 October 2011 / Accepted: 7 November 2011 / Published: 11 November 2011
Abstract: Serine/threonine protein kinase C βII isoform (PKCβII) or the pain receptor transient receptor potential vanilloid 1 (TRPV1) have been separately implicated in mediating heat hyperalgesia during inflammation or diabetic neuropathy. However, detailed information on the role of PKC βII in nociceptive signaling mediated by TRPV1 is lacking. This study presents evidence for activation and translocation of the PKC βII isoform as a signaling event in nociception mediated by activation of TRPV1 by capsaicin. We show that capsaicin induces translocation of cytosolic PKCβII isoform fused with enhanced green fluorescence protein (PKCβII-EGFP) in dorsal root ganglion (DRG) neurons. We also show capsaicin-induced translocation in Chinese Hamster Ovarian (CHO) cells co-transfected with TRPV1 and PKCβII-EGFP, but not in CHO cells expressing PKCβII-EGFP alone. By contrast, the PKC activator phorbol-12-myristate-13-acetate (PMA) induced translocation of PKCβII-EGFP which was sustained and independent of calcium or TRPV1. In addition PMA-induced sensitization of TRPV1 to capsaicin response in DRG neurons was attenuated by PKCβII blocker CGP 53353. Capsaicin response via TRPV1 in the DRG neurons was confirmed by TRPV1 antagonist AMG 9810. These results suggested a novel and potential signaling link between PKCβII and TRPV1. These cell culture models provide a platform for investigating mechanisms of painful neuropathies mediated by nociceptors expressing the pain sensing gene TRPV1, and its regulation by the PKC isoform PKCβII.
Keywords: pain; protein kinase C; transient receptor potential vanilloid-1; real-time translocation; dorsal root ganglion neurons; nociceptive signaling
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Mandadi, S.; Armati, P.J.; Roufogalis, B.D. Real-Time Translocation and Function of PKCβII Isoform in Response to Nociceptive Signaling via the TRPV1 Pain Receptor. Pharmaceuticals 2011, 4, 1503-1517.
Mandadi S, Armati PJ, Roufogalis BD. Real-Time Translocation and Function of PKCβII Isoform in Response to Nociceptive Signaling via the TRPV1 Pain Receptor. Pharmaceuticals. 2011; 4(11):1503-1517.
Mandadi, Sravan; Armati, Patricia J.; Roufogalis, Basil D. 2011. "Real-Time Translocation and Function of PKCβII Isoform in Response to Nociceptive Signaling via the TRPV1 Pain Receptor." Pharmaceuticals 4, no. 11: 1503-1517.