- Research Article
Cytosolic phospholipase A2 regulation in the hibernating thirteen-lined ground squirrel
Cellular & Molecular Biology Letters volume 12, Article number: 621 (2007)
Cytosolic calcium-dependent phospholipase A2 (cPLA2) has multiple roles including production of arachidonic acid (a key player in cellular signaling pathways) and membrane remodeling. Additionally, since catabolism of arachidonic acid generates free radicals, the enzyme is also implicated in ischemic injury to mammalian organs. Regulation of cPLA2 could be important in the suppression and prioritization of cellular pathways in animals that undergo reversible transitions into hypometabolic states. The present study examines the responses and regulation of cPLA2 in skeletal muscle and liver of hibernating thirteen-lined ground squirrels, Spermophilus tridecemlineatus. cPLA2 activity decreased significantly by 43% in liver during hibernation, compared with euthermic controls, and Km values for arachidonoyl thio-PC substrate fell in both organs during hibernation to 61% in liver and 28% in muscle of the corresponding euthermic value. To determine whether these responses were due to a change in the phosphorylation state of the enzyme, Western blotting was employed using antibodies recognizing phospho-Ser505 on α-cPLA2. The amount of phosphorylated α-cPLA2 in hibernator liver was just 38% of the value in euthermic liver. Furthermore, incubation of liver extracts under conditions that enhanced protein phosphatase action caused a greater reduction in the detectable amount of phospho-Ser505 enzyme content in euthermic, versus hibernator, extracts. The data are consistent with a suppression of cPLA2 function during torpor via enzyme dephosphorylation, an action that may contribute to the well-developed ischemia tolerance and lack of oxidative damage found in hibernating species over cycles of torpor and arousal.
- cPLA2 :
cytosolic calcium-dependent phospholipase A2
mitogen-activated protein kinase
Katsuki, H. and Okuda, S. Arachidonic acid as a neurotoxic and neurotrophic substance. Prog. Neurobiol.. 46 (1995) 607–636.
Asai, K., Hirabayashi, T., Houjou, T., Uozumi, N., Taguchi, R. and Shimizu, T. Human group IVC phospholipase A2 (PLA2γ). J. Biol. Chem. 278 (2003) 8809–8814.
Brown, W. J., Chambers, K. and Doody, A. Phospholipase A2 (PLA2) enzymes in membrane trafficking: mediators of membrane shape and function. Traffic 4 (2003) 214–221.
Han, C., Demetris, A. J., Michalopoulos, G., Shelhamer, J. H. and Wu, T. 85-kDa PLA2 plays a critical role in PPAR-mediated gene transcription in human hepatoma cells. Am. J. Physiol. 282 (2002) G586–G597.
Dessen, A. Structure and mechanism of human cytosolic phospholipase A2. Biochim. Biophys. Acta 1488 (2000) 40–47.
Hirabayashi, T. and Shimizu, T. Location and regulation of cytosolic phospholipase A2. Biochim. Biophys. Acta 1488 (2000) 124–138.
Balsinde, J., Balboa, M. A., Insel, P. A. and Dennis, E. A. Regulation and inhibition of phospholipase A2. Annu. Rev. Pharmacol. Toxicol. 39 (1999) 175–189.
Shimizu, T., Ohto, T. and Kita, Y. Cytosolic phospholipase A2: biochemical properties and physiological roles. IUBMB Life 58 (2006) 328–333.
Zhu, X., Sano, H., Kim, K. P., Sano, A., Boetticher, E., Munoz, N. M., Cho, W. and Leff, A. R. Role of mitogen-activated protein kinase-mediated cytosolic phospholipase A2 activation in arachidonic acid metabolism in human eosinophils. J. Immunol. 167 (2001) 461–468.
Zhou, H., Das, S. and Murthy, K.S. Erk1/2-and p38 MAP kinase-dependent phosphorylation and activation of PLA2 by m3 and m2 receptors. Am. J. Physiol. 284 (2003) G472–G480.
Muralikrishna Adibhatla, R. and Hatcher, J.F. Phospholipase A2, reactive oxygen species, and lipid peroxidation in cerebral ischemia. Free Radic. Biol. Med. 40 (2006) 376–387.
Hermes-Lima, M., Storey, J.M. and Storey, K.B. Antioxidant defenses and animal adaptation to oxygen availability during environmental stress. in: Cell and Molecular Responses to Stress (Storey, K.B. and Storey, J.M.), Elsevier Press, Amsterdam, 2001, 263–287.
Storey K. B. and Storey J. M. Mammalian hibernation: biochemical adaptation and gene expression. in: Functional Metabolism: Regulation and Adaptation (Storey, K.B., Ed.), Wiley-Liss, Hoboken, 2004, 443–471.
Storey, K.B. and Storey, J.M. Metabolic rate depression in animals: transcriptional and translational controls. Biol. Rev. Camb. Philos. Soc. 79 (2004) 207–233.
Brustovetsky, N. N., Mayesky, E. I., Grishina, E. V., Gogvadze, V. G. and Amerkhanov, Z. G. Regulation of the rate of respiration and oxidative phosphorylation in liver mitochondria from hibernating ground squirrels, Citellus undulatus. Comp. Biochem. Physiol. B 94 (1989) 537–541.
Brustovetsky, N. N., Egorova, M. V. and Mayevsky, E. I. Regulation of oxidative activity and ΔΨ of liver mitochondria of active and hibernating gophers. The role of phospholipase A2. Comp. Biochem. Physiol. B 102 (1992) 635–638.
Brooks, S.P.J. A program for analyzing enzyme rate data obtained from a microplate reader. BioTechniques 17 (1994) 1155–1161.
Brooks, S.P.J. A simple computer program with statistical tests for the analysis of enzyme kinetics. BioTechniques 13 (1992) 906–911.
Morin, P. and Storey, K. B. Cloning and expression of hypoxia-inducible factor 1α from the hibernating ground squirrel, Spermophilus tridecemlineatus. Biochim. Biophys. Acta 1729 (2005) 32–40.
Mamady, H. and Storey, K. B. Up-regulation of the endoplasmic reticulum molecular chaperone GRP78 during hibernation in thirteen-lined ground squirrels. Mol. Cell. Biochem. 292 (2006) 89–98.
Drew, K.L., Toien, O., Rivera, P.M., Smith, M.A., Perry, G. and Rice, M.E. Role of the antioxidant ascorbate in hibernation and warming from hibernation. Comp. Biochem. Physiol. C 133 (2002) 483–492.
Buzadzic, B., Spasic, M. Saicic, Z.S., Radojicic, R., Petrovic, V.M. and Halliwell, B. Antioxidant defenses in the ground squirrel Citellus citellus. 2. The effect of hibernation, Free Radic. Biol. Med. 9 (1990) 407–413.
Barja de Quiroga, G. Brown fat thermogenesis and exercise: two examples of physiological oxidative stress? Free Radic. Biol. Med. 13 (1992) 325–340.
Eddy, S.F., McNally, J.D. and Storey, K.B. Up-regulation of a thioredoxin peroxidase-like protein, proliferation associated gene, in hibernating bats. Arch. Biochem. Biophys. 435 (2005) 101–111.
Clark, J. D., Schievella, A. R., Nalefski, E. A. and Lin, L. L. Cytosolic phospholipase A2. J. Lipid Med. Cell Signal. 12 (1995) 83–117.
Chakraborti, S. Phospholipase A2 isoforms: a perspective. Cell. Signal. 15 (2003) 637–665.
Bailleux, A., Wendum, D., Audubert, F., Jouniau, A., Koumanov, K., Trugnan, G. and Masliah, J. Cytosolic phospholipase A2/p11 interaction controls arachidonic acid release as a function of epithelial cell confluence. Biochem. J. 378 (2004) 307–315.
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Woods, A.K., Storey, K.B. Cytosolic phospholipase A2 regulation in the hibernating thirteen-lined ground squirrel. Cell Mol Biol Lett 12, 621 (2007). https://doi.org/10.2478/s11658-007-0036-8
- Metabolic rate depression
- Arachidonic acid production
- Reversible phosphorylation
- Spermophilus tridecemlineatus