KATSUYA HIRASAKA, PhD
My research interests are focused on skeletal muscle metabolism and pathophysiology. In my former lab in Tokushima, Japan, I identified reactive oxidant species and the E3 ubiquitin ligase Cbl-b as critical components of the proteolytic cascade that leads to muscle degeneration in response to lack of use or microgravity. In the Mills lab, my project explores how intracellular redox signals coordinate skeletal muscle fatty acid metabolism, insulin sensitivity, and mitochondrial thermogenesis regulated by uncoupling protein 3 (UCP3).
Mikura M, Yamaoka I, Doi M, Kawano Y, Nakayama M, Nakao R, Hirasaka K, Okumura Y, Nikawa T (2009) Glucose infusion suppresses surgery-induced muscle protein breakdown by inhibiting ubiquitin-proteasome pathway in rats Anesthesiology 110: 81-88
Hirasaka K, Kohno S, Goto J, Furochi H, Mawatari K, Harada N, Hosaka T, Nakaya Y, Ishidoh K, Obata T, Ebina Y, Gu H, Takeda S, Kishi K, Nikawa T (2007) Deficiency of Cbl-b gene enhances infiltration and activation of macrophages in adipose tissue and causes peripheral insulin resistance in mice Diabetes 56: 2511-2522
Suzue N, Nikawa T, Onishi Y, Yamada C, Hirasaka K, Ogawa T, Furochi H, Kosaka H, Ishidoh K, Gu H, Takeda S, Ishimaru N, Hayashi Y, Yamamoto H, Kishi K, Yasui N (2006) Ubiquitin ligase Cbl-b downregulates bone formation through suppression of IGF-I signaling in osteoblasts during denervation J Bone Miner Res 21: 722-734
Hirasaka K, Nikawa T, Yuge L, Ishihara I, Higashibata A, Ishioka N, Okubo A, Miyashita T, Suzue N, Ogawa T, Oarada M, Kishi K (2005) Clinorotation prevents differentiation of rat myoblastic L6 cells in association with reduced NF-kappa B signaling Biochim Biophys Acta 1743: 130-140
Nikawa T, Ishidoh K, Hirasaka K, Ishihara I, Ikemoto M, Kano M, Kominami E, Nonaka I, Ogawa T, Adams GR, Baldwin Km, Yasui N, Kishi K, Takeda S (2004) Skeletal muscle gene expression in space-flown rats FASEB J 18: 522-524
Uncoupling proteins (UCPs) are mitochondrial transmembrane proteins that waste energy in the form of heat. Uncoupling protein 3 is enriched in skeletal muscle, an established thermogenic organ. UCP3 knockout (KO) mice almost completely lack the hyperthermic responses to the widely-abused drugs ecstasy and methamphetamine. My project uses multiple mouse strains and cultured primary and secondary myocytes cell lines to determine the physiological and cellular mechanisms of UCP3-driven thermogenesis.
M. Alexander Kenaston, Katsuya Hirasaka, Kristin Fathe, Sara M Nowinski, Matthew E Pfeiffer, Xianmei Yang, Takeshi Nikawa, and Edward M Mills. IDENTIFICATION OF THE FATTY ACID-SENSITIVE INTERACTION OF MITOCHONDRIAL UNCOUPLING PROTEIN 3 AND Δ3,5Δ2,4 DIENOYL-COA ISOMERASE IN SKELETAL MUSCLE (2011) Diabetes (in final revision, June 2011).
Banks ML, Buzard SK, Gehret CM, Monroy AN, Kenaston MA, Mills EM, Sprague JE (2009) Pharmacodynamic characterization of insulin on MDMA-induced thermogenesis Eur J Pharmacol 615: 257-261
Wyeth RP, Mills EM, Ullman A, Kenaston MA, Burwell J, Sprague JE (2009) The hyperthermia mediated by 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) is sensitive to sex differences Toxicol Appl Pharmacol 235: 33-38
Uncoupling proteins are highly conserved members of the mitochondrial anion superfamily. Unlike other UCP homologues, only UCP4 is present in the nematode Caenorhabditis elegans (C. elegans), suggesting that it is the ancestral uncoupling protein from which other homologues diverged. UCP4 knockout worms are obese, accumulate triglycerides, and have deficiencies in the import of mitochondrial substrates. My project involves molecular, cellular, and biochemical approaches to characterize the physiologic functions of UCP4 and the mechanisms by which UCP4 regulates mitochondrial functions.
Matthew Pfeiffer, Ernst-Bernhard Kayser, Xianmei Yang, Ellen Abramson, Monte A. Kenaston, Cory U Lago, Herng-Hsiang Lo, Margaret Sedensky, Adam Lunceford, Catherine Clark, Sarah Wu, Christopher McLeod, Toren Finkel, Philip Morgan, and Edward M Mills. Caenorhabditis elegans UCP4 controls complex II-mediated oxidative phosphorylation through succinate transport (2011) J. Biol. Chem. (Under Review, June 2011).
Kenaston MA, Abramson E, Pfeiffer ME, Mills EM (2009) Chapter 70: Toxicology of Skeletal Muscle General and Applied Toxicology 3rd Ed. Wiley, ISBN#978-470-72327-2
Mills EM, Weaver KL, Abramson E, Pfeiffer M, Sprague JE (2008) Influence of dietary fats on ecstasy-induced hyperthermia Brit J Pharmacol 151: 1103-1108
Pharmacology & Toxicology
College of Pharmacy
The University of Texas
107 W. Dean Keeton
Austin, TX, USA
Email Address: pharmtox
"Drugs, the Brain and Behavior" is co-authored by Dr. Carlton Erickson, the college's associate dean for research and graduate studies, and Dr. John Brick, executive director of Intoxikon International.