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Expression and localization of the diacylglycerol kinase family and of phosphoinositide signaling molecules in adrenal gland

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Abstract

Adrenal glands play a central role in the secretion of steroid hormones and catecholamines. Previous studies have revealed that molecules engaged in phosphoinositide (PI) turnover are expressed in the adrenal gland, suggesting the importance of PI signaling in adrenal signal transduction. Diacylglycerol kinase (DGK) catalyzes the phosphorylation of diacylglycerol (DG), a major second messenger in the PI signaling cascade. The DGK family is expressed in distinct patterns in endocrine organs at the mRNA and protein levels. Nevertheless, little is known about the characteristics and morphological aspects of DGKs in the adrenal gland. We have performed immunohistochemical analyses to investigate the expression and localization of DGK isozymes, together with PI signaling molecules, in the adrenal gland at the protein level. Our results show that the DGK family and a set of PI signaling molecules are expressed intensely in zona glomerulosa cells and medullary chromaffin cells in the adrenal gland. In adrenal cells, DGKγ localizes to the Golgi complex, DGKε to the plasma membrane, and DGKζ to the nucleus. These findings show the distinct expression and subcellular localization of DGK isozymes and PI signaling molecules in the adrenal gland, suggesting that each DGK isozyme has a role in signal transduction in adrenal cells, especially in the zona glomerulosa and medulla.

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References

  • Anand U, Facer P, Yiangou Y, Sinisi M, Fox M, McCarthy T, Bountra C, Korchev YE, Anand P (2013) Angiotensin II type 2 receptor (AT2 R) localization and antagonist-mediated inhibition of capsaicin responses and neurite outgrowth in human and rat sensory neurons. Eur J Pain 17:1012–1026

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Aunis D (1998) Exocytosis in chromaffin cells of the adrenal medulla. Int Rev Cytol 181:213–320

    Article  CAS  PubMed  Google Scholar 

  • Berk BC, Corson MA (1997) Angiotensin II signal transduction in vascular smooth muscle: role of tyrosine kinases. Circ Res 80:607–616

    Article  CAS  PubMed  Google Scholar 

  • Bernstein KE, Ali MS, Sayeski PP, Semeniuk D, Marrero MB (1998) New insights into the cellular signaling of seven transmembrane receptors: the role of tyrosine phosphorylation. Lab Invest 78:3–7

    CAS  PubMed  Google Scholar 

  • Bittner MA, Holz RW (2005) Phosphatidylinositol-4,5-bisphosphate: actin dynamics and the regulation of ATP-dependent and -independent secretion. Mol Pharmacol 67:1089–1098

    Article  CAS  PubMed  Google Scholar 

  • Bunn SJ, Dunkley PR (1997) Histamine-stimulated phospholipase C signalling in the adrenal chromaffin cell: effects on inositol phospholipid metabolism and tyrosine hydroxylase phosphorylation. Clin Exp Pharmacol Physiol 24:624–631

    Article  CAS  PubMed  Google Scholar 

  • Cockcroft S, Thomas GM (1992) Inositol-lipid-specific phospholipase C isoenzymes and their differential regulation by receptors. Biochem J 288:1–14

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cote M, Payet MD, Dufour MN, Guillon G, Gallo-Payet N (1997) Association of the G protein alpha(q)/alpha11-subunit with cytoskeleton in adrenal glomerulosa cells: role in receptor-effector coupling. Endocrinology 138:3299–3307

    CAS  PubMed  Google Scholar 

  • Danser AH, Anand P (2014) The angiotensin II type 2 receptor for pain control. Cell 157:1504–1506

    Article  CAS  PubMed  Google Scholar 

  • Frei N, Weissenberger J, Beck-Sickinger AG, Hofliger M, Weis J, Imboden H (2001) Immunocytochemical localization of angiotensin II receptor subtypes and angiotensin II with monoclonal antibodies in the rat adrenal gland. Regul Pept 101:149–155

    Article  CAS  PubMed  Google Scholar 

  • Gasc JM, Shanmugam S, Sibony M, Corvol P (1994) Tissue-specific expression of type 1 angiotensin II receptor subtypes. An in situ hybridization study. Hypertension 24:531–537

    Article  CAS  PubMed  Google Scholar 

  • Giles ME, Fernley RT, Nakamura Y, Moeller I, Aldred GP, Ferraro T, Penschow JD, McKinley MJ, Oldfield BJ (1999) Characterization of a specific antibody to the rat angiotensin II AT1 receptor. J Histochem Cytochem 47:507–516

    Article  CAS  PubMed  Google Scholar 

  • Goto K, Kondo H (2004) Functional implications of the diacylglycerol kinase family. Adv Enzym Regul 44:187–199

    Article  CAS  Google Scholar 

  • Goto K, Watanabe M, Kondo H, Yuasa H, Sakane F, Kanoh H (1992) Gene cloning, sequence, expression and in situ localization of 80 kDa diacylglycerol kinase specific to oligodendrocyte of rat brain. Brain Res Mol Brain Res 16:75–87

    Article  CAS  PubMed  Google Scholar 

  • Goto K, Nakano T, Hozumi Y (2006) Diacylglycerol kinase and animal models: the pathophysiological roles in the brain and heart. Adv Enzym Regul 46:192–202

    Article  CAS  Google Scholar 

  • Goto K, Hozumi Y, Nakano T, Saino SS, Kondo H (2007) Cell biology and pathophysiology of the diacylglycerol kinase family: morphological aspects in tissues and organs. Int Rev Cytol 264:25–63

    Article  CAS  PubMed  Google Scholar 

  • Goto K, Tanaka T, Nakano T, Okada M, Hozumi Y, Topham MK, Martelli AM (2014) DGKzeta under stress conditions: "to be nuclear or cytoplasmic, that is the question". Adv Biol Regul 54:242–253

    Article  CAS  PubMed  Google Scholar 

  • Griendling KK, Ushio-Fukai M, Lassegue B, Alexander RW (1997) Angiotensin II signaling in vascular smooth muscle. New concepts. Hypertension 29:366–373

    Article  CAS  PubMed  Google Scholar 

  • Hasegawa H, Nakano T, Hozumi Y, Takagi M, Ogino T, Okada M, Iseki K, Kondo H, Watanabe M, Martelli AM, Goto K (2008) Diacylglycerol kinase zeta is associated with chromatin, but dissociates from condensed chromatin during mitotic phase in NIH3T3 cells. J Cell Biochem 105:756–765

    Article  CAS  PubMed  Google Scholar 

  • Hokin MR, Benfey BG, Hokin LE (1958) Phospholipides and adrenaline secretion in guinea pig adrenal medulla. J Biol Chem 233:814–817

    CAS  PubMed  Google Scholar 

  • Hozumi Y, Goto K (2012) Diacylglycerol kinase beta in neurons: functional implications at the synapse and in disease. Adv Biol Regul 52:315–325

    Article  CAS  PubMed  Google Scholar 

  • Hozumi Y, Ito T, Nakano T, Nakagawa T, Aoyagi M, Kondo H, Goto K (2003) Nuclear localization of diacylglycerol kinase zeta in neurons. Eur J Neurosci 18:1448–1457

    Article  PubMed  Google Scholar 

  • Hozumi Y, Fukaya M, Adachi N, Saito N, Otani K, Kondo H, Watanabe M, Goto K (2008) Diacylglycerol kinase beta accumulates on the perisynaptic site of medium spiny neurons in the striatum. Eur J Neurosci 28:2409–2422

    Article  PubMed  Google Scholar 

  • Hozumi Y, Watanabe M, Otani K, Goto K (2009) Diacylglycerol kinase beta promotes dendritic outgrowth and spine maturation in developing hippocampal neurons. BMC Neurosci 10:99

    Article  PubMed Central  PubMed  Google Scholar 

  • Hozumi Y, Watanabe M, Goto K (2010) Signaling cascade of diacylglycerol kinase beta in the pituitary intermediate lobe: dopamine D2 receptor/phospholipase Cbeta4/diacylglycerol kinase beta/protein kinase Calpha. J Histochem Cytochem 58:119–129

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hozumi Y, Matsui H, Sakane F, Watanabe M, Goto K (2013) Distinct expression and localization of diacylglycerol kinase isozymes in rat retina. J Histochem Cytochem 61:462–476

    Article  PubMed Central  PubMed  Google Scholar 

  • Ito T, Hozumi Y, Sakane F, Saino-Saito S, Kanoh H, Aoyagi M, Kondo H, Goto K (2004) Cloning and characterization of diacylglycerol kinase iota splice variants in rat brain. J Biol Chem 279:23317–23326

    Article  CAS  PubMed  Google Scholar 

  • Johren O, Inagami T, Saavedra JM (1995) AT1A, AT1B, and AT2 angiotensin II receptor subtype gene expression in rat brain. Neuroreport 6:2549–2552

    Article  CAS  PubMed  Google Scholar 

  • Kanoh H, Yamada K, Sakane F (1990) Diacylglycerol kinase: a key modulator of signal transduction? Trends Biochem Sci 15:47–50

    Article  CAS  PubMed  Google Scholar 

  • Kim S, Iwao H (2000) Molecular and cellular mechanisms of angiotensin II-mediated cardiovascular and renal diseases. Pharmacol Rev 52:11–34

    CAS  PubMed  Google Scholar 

  • Kobayashi N, Hozumi Y, Ito T, Hosoya T, Kondo H, Goto K (2007) Differential subcellular targeting and activity-dependent subcellular localization of diacylglycerol kinase isozymes in transfected cells. Eur J Cell Biol 86:433–444

    Article  CAS  PubMed  Google Scholar 

  • Lania A, Mantovani G, Spada A (2001) G protein mutations in endocrine diseases. Eur J Endocrinol 145:543–559

    Article  CAS  PubMed  Google Scholar 

  • Li D, Urs AN, Allegood J, Leon A, Merrill AH Jr, Sewer MB (2007) Cyclic AMP-stimulated interaction between steroidogenic factor 1 and diacylglycerol kinase theta facilitates induction of CYP17. Mol Cell Biol 27:6669–6685

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Marley PD (2003) Mechanisms in histamine-mediated secretion from adrenal chromaffin cells. Pharmacol Ther 98:1–34

    Article  CAS  PubMed  Google Scholar 

  • Martelli AM, Fala F, Faenza I, Billi AM, Cappellini A, Manzoli L, Cocco L (2004) Metabolism and signaling activities of nuclear lipids. Cell Mol Life Sci 61:1143–1156

    Article  CAS  PubMed  Google Scholar 

  • Martelli AM, Ognibene A, Buontempo F, Fini M, Bressanin D, Goto K, McCubrey JA, Cocco L, Evangelisti C (2011) Nuclear phosphoinositides and their roles in cell biology and disease. Crit Rev Biochem Mol Biol 46:436–457

    Article  CAS  PubMed  Google Scholar 

  • Matsui H, Hozumi Y, Tanaka T, Okada M, Nakano T, Suzuki Y, Iseki K, Kakehata S, Topham MK, Goto K (2014) Role of the N-terminal hydrophobic residues of DGKepsilon in targeting the endoplasmic reticulum. Biochim Biophys Acta 1842:1440–1450

    Article  PubMed  Google Scholar 

  • Mendelsohn FA, Allen AM, Chai SY, McKinley MJ, Oldfield BJ, Paxinos G (1990) The brain angiotensin system: insights from mapping its components. Trends Endocrinol Metab 1:189–198

    Article  CAS  PubMed  Google Scholar 

  • Merida I, Avila-Flores A, Merino E (2008) Diacylglycerol kinases: at the hub of cell signalling. Biochem J 409:1–18

    Article  CAS  PubMed  Google Scholar 

  • Murphy TJ, Alexander RW, Griendling KK, Runge MS, Bernstein KE (1991) Isolation of a cDNA encoding the vascular type-1 angiotensin II receptor. Nature 351:233–236

    Article  CAS  PubMed  Google Scholar 

  • Nakamura M, Sato K, Fukaya M, Araishi K, Aiba A, Kano M, Watanabe M (2004) Signaling complex formation of phospholipase Cbeta4 with metabotropic glutamate receptor type 1alpha and 1,4,5-trisphosphate receptor at the perisynapse and endoplasmic reticulum in the mouse brain. Eur J Neurosci 20:2929–2944

    Article  PubMed  Google Scholar 

  • Nakano T, Hozumi Y, Goto K, Wakabayashi I (2009) Localization of diacylglycerol kinase epsilon on stress fibers in vascular smooth muscle cells. Cell Tissue Res 337:167–175

    Article  CAS  PubMed  Google Scholar 

  • Nakano T, Hozumi Y, Goto K, Wakabayashi I (2012) Involvement of diacylglycerol kinase gamma in modulation of iNOS synthesis in Golgi apparatus of vascular endothelial cells. Naunyn Schmiedebergs Arch Pharmacol 385:787–795

    Article  CAS  PubMed  Google Scholar 

  • Nishizuka Y (1992) Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science 258:607–614

    Article  CAS  PubMed  Google Scholar 

  • Nomura S, Fukaya M, Tsujioka T, Wu D, Watanabe M (2007) Phospholipase Cbeta3 is distributed in both somatodendritic and axonal compartments and localized around perisynapse and smooth endoplasmic reticulum in mouse Purkinje cell subsets. Eur J Neurosci 25:659–672

    Article  PubMed  Google Scholar 

  • Oomori Y, Habara Y, Kanno T (1998) Muscarinic and nicotinic receptor-mediated Ca2+ dynamics in rat adrenal chromaffin cells during development. Cell Tissue Res 294:109–123

    Article  CAS  PubMed  Google Scholar 

  • O'Sullivan KM, Bunn SJ (2006) Phospholipase C isozymes are differentially distributed in the rat adrenal medulla. Neurosci Lett 396:212–216

    Article  PubMed  Google Scholar 

  • Oyesiku NM, Evans CO, Brown MR, Blevins LS, Tindall GT, Parks JS (1997) Pituitary adenomas: screening for G alpha q mutations. J Clin Endocrinol Metab 82:4184–4188

    CAS  PubMed  Google Scholar 

  • Rhee SG, Suh PG, Ryu SH, Lee SY (1989) Studies of inositol phospholipid-specific phospholipase C. Science 244:546–550

    Article  CAS  PubMed  Google Scholar 

  • Rice AS, Dworkin RH, McCarthy TD, Anand P, Bountra C, McCloud PI, Hill J, Cutter G, Kitson G, Desem N, Raff M (2014) EMA401, an orally administered highly selective angiotensin II type 2 receptor antagonist, as a novel treatment for postherpetic neuralgia: a randomised, double-blind, placebo-controlled phase 2 clinical trial. Lancet 383:1637–1647

    Article  CAS  PubMed  Google Scholar 

  • Roberts-Thomson EL, Herd LM, Saunders HI, Dunkley PR, Bunn SJ (2004) The tyrosine [correction of tryrosine] phosphorylation and cytoskeletal translocation of phospholipase C gamma 1 in bovine adrenal medullary chromaffin cells. Neurochem Res 29:1847–1855

    Article  CAS  PubMed  Google Scholar 

  • Ron D, Kazanietz MG (1999) New insights into the regulation of protein kinase C and novel phorbol ester receptors. FASEB J 13:1658–1676

    CAS  PubMed  Google Scholar 

  • Sakane F, Imai S, Kai M, Yasuda S, Kanoh H (2007) Diacylglycerol kinases: why so many of them? Biochim Biophys Acta 1771:793–806

    Article  CAS  PubMed  Google Scholar 

  • Sarria R, Diez J, Losada J, Donate-Oliver F, Kuhn R, Grandes P (2006) Immunocytochemical localization of metabotropic (mGluR2/3 and mGluR4a) and ionotropic (GluR2/3) glutamate receptors in adrenal medullary ganglion cells. Histol Histopathol 21:141–147

    CAS  PubMed  Google Scholar 

  • Schieffer B, Bernstein KE, Marrero MB (1996) The role of tyrosine phosphorylation in angiotensin II mediated intracellular signaling and cell growth. J Mol Med (Berl) 74:85–91

    Article  CAS  Google Scholar 

  • Schober A, Huber K, Fey J, Unsicker K (1998) Distinct populations of macrophages in the adult rat adrenal gland: a subpopulation with neurotrophin-4-like immunoreactivity. Cell Tissue Res 291:365–373

    Article  CAS  PubMed  Google Scholar 

  • Shapiro BA, Olala L, Arun SN, Parker PM, George MV, Bollag WB (2010) Angiotensin II-activated protein kinase D mediates acute aldosterone secretion. Mol Cell Endocrinol 317:99–105

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Timmermans PB, Chiu AT, Herblin WF, Wong PC, Smith RD (1992) Angiotensin II receptor subtypes. Am J Hypertens 5:406–410

    Article  CAS  PubMed  Google Scholar 

  • Timmermans PB, Wong PC, Chiu AT, Herblin WF, Benfield P, Carini DJ, Lee RJ, Wexler RR, Saye JA, Smith RD (1993) Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol Rev 45:205–251

    CAS  PubMed  Google Scholar 

  • Topham MK (2006) Signaling roles of diacylglycerol kinases. J Cell Biochem 97:474–484

    Article  CAS  PubMed  Google Scholar 

  • Tsuzuki S, Ichiki T, Nakakubo H, Kitami Y, Guo DF, Shirai H, Inagami T (1994) Molecular cloning and expression of the gene encoding human angiotensin II type 2 receptor. Biochem Biophys Res Commun 200:1449–1454

    Article  CAS  PubMed  Google Scholar 

  • Wang QJ (2006) PKD at the crossroads of DAG and PKC signaling. Trends Pharmacol Sci 27:317–323

    Article  CAS  PubMed  Google Scholar 

  • Yoshida T, Fukaya M, Uchigashima M, Miura E, Kamiya H, Kano M, Watanabe M (2006) Localization of diacylglycerol lipase-alpha around postsynaptic spine suggests close proximity between production site of an endocannabinoid, 2-arachidonoyl-glycerol, and presynaptic cannabinoid CB1 receptor. J Neurosci 26:4740–4751

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Du G (2009) Phosphatidic acid signaling regulation of Ras superfamily of small guanosine triphosphatases. Biochim Biophys Acta 1791:850–855

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Correspondence to Yasukazu Hozumi.

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This work was supported by Grants-in-Aid from The Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (Y.H., K.G.).

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Hozumi, Y., Akimoto, R., Suzuki, A. et al. Expression and localization of the diacylglycerol kinase family and of phosphoinositide signaling molecules in adrenal gland. Cell Tissue Res 362, 295–305 (2015). https://doi.org/10.1007/s00441-015-2199-3

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