Klotho regulates retinal pigment epithelial functions and protects against oxidative stress

Journal of Neuroscience

Volumn 33, Issue 41, 2013, Pages 16346-16359

  Kokkinaki, Maria ^a   Abu Asab, Mones ^c   Gunawardena, Nishantha ^a   Ahern, Gerard ^a   Javidnia, Monica ^a   Young, John ^b   Golestaneh, Nady ^a  

^a GEORGETOWN UNIVERSITY MEDICAL CENTER   (United States)

^b HOWARD UNIVERSITY COLLEGE OF MEDICINE   (United States)

^c NATIONAL EYE INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIC AMP DEPENDENT PROTEIN KINASE; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; KLOTHO PROTEIN; LEVODOPA; MANGANESE SUPEROXIDE DISMUTASE; MELANIN; MICROPHTHALMIA ASSOCIATED TRANSCRIPTION FACTOR; MONOPHENOL MONOOXYGENASE; REACTIVE OXYGEN METABOLITE; SOMATOMEDIN C; VASCULOTROPIN; VASCULOTROPIN A; VASCULOTROPIN RECEPTOR 2;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DRUSEN; ENZYME LINKED IMMUNOSORBENT ASSAY; FLUOROMETRY; GENE CONTROL; GENE EXPRESSION; GENE SILENCING; HISTOLOGY; HUMAN; HUMAN CELL; IMMUNOBLOTTING; IMMUNOHISTOCHEMISTRY; MASS SPECTROMETRY; MELANOGENESIS; MOUSE; NONHUMAN; OXIDATIVE STRESS; PHAGOCYTOSIS; PHOTORECEPTOR CELL; PIGMENT EPITHELIUM; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; RADIOIMMUNOPRECIPITATION; REAL TIME POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; TRANSMISSION ELECTRON MICROSCOPY;

ANIMALS; CELL LINE; GENE EXPRESSION REGULATION; GLUCURONIDASE; HUMANS; IMMUNOBLOTTING; IMMUNOHISTOCHEMISTRY; IMMUNOPRECIPITATION; MASS SPECTROMETRY; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; OXIDATIVE STRESS; REAL-TIME POLYMERASE CHAIN REACTION; RETINAL DEGENERATION; RETINAL PIGMENT EPITHELIUM; SIGNAL TRANSDUCTION;

EID: 84885102096     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.0402-13.2013     Document Type: Article

References (95)

1. Abdelsalam A, Del Priore L, Zarbin MA (1999) Drusen in age-related macular degeneration: pathogenesis, natural course, and laser photocoagulationinduced regression. Surv Ophthalmol 44:1-29. CrossRef Medline
2. Beitz E, Volkel H, Guo Y, Schultz JE (1998) Adenylyl cyclase type 7 is the predominant isoform in the bovine retinal pigment epithelium. Acta Anat (Basel) 162:157-162. CrossRef Medline
3. Bertolotto C, Abbe P, Hemesath TJ, Bille K, Fisher DE, Ortonne JP, Ballotti R (1998) Microphthalmia gene product as a signal transducer in cAMPinduced differentiation of melanocytes. J Cell Biol 142:827-835. CrossRef Medline
4. Bonilha VL (2008) Age and disease-related structural changes in the retinal pigment epithelium. Clin Ophthalmol 2:413-424. CrossRef Medline
5. Boulton M, Dayhaw-Barker P (2001) The role of the retinal pigment epithelium: topographical variation and ageing changes. Eye (Lond) 15:384-389. CrossRef Medline
6. Boulton M, Rozanowska M, Rozanowski B, Wess T (2004) The photoreactivity of ocular lipofuscin. Photochem Photobiol Sci 3:759-764. CrossRef Medline
7. Burns MS, Hartz MJ (1992) The retinal pigment epithelium induces fenestration of endothelial cells in vivo. Curr Eye Res 11:863-873. CrossRef Medline
8. Cai J, Nelson KC, Wu M, Sternberg P Jr, Jones DP (2000) Oxidative damage and protection of the RPE. Prog Retin Eye Res 19:205-221. CrossRef Medline
9. Carracedo J, Buendía P, Merino A, Madueno JA, Peralbo E, Ortiz A, Martín-Malo A, Aljama P, Rodríguez M, Ramírez R (2012) Klotho modulates the stress response in human senescent endothelial cells. Mech Ageing Dev 133:647-654. CrossRef Medline
10. Cha SK, Ortega B, Kurosu H, Rosenblatt KP, Kuro O M, Huang CL (2008) Removal of sialic acid involving Klotho causes cell-surface retention of TRPV5 channel via binding to galectin-1. Proc Natl Acad Sci U S A 105: 9805-9810. CrossRef Medline
11. Chen CD, Sloane JA, Li H, Aytan N, Giannaris EL, Zeldich E, Hinman JD, Dedeoglu A, Rosene DL, Bansal R, Luebke JI, Kuro-o M, Abraham CR (2013) The antiaging protein Klotho enhances oligodendrocyte maturation and myelination of the CNS. J Neurosci 33:1927-1939. CrossRef Medline
12. Chesik D, Wilczak N, De Keyser J (2008) IGF-1 regulates cAMP levels in astrocytes through a beta2-adrenergic receptor-dependant mechanism. Int J Med Sci 5:240-243. CrossRef Medline
13. Cho Y, Cao X, Shen D, Tuo J, Parver LM, Rickles FR, Chan CC (2011) Evidence for enhanced tissue factor expression in age-related macular degeneration. Lab Invest 91:519-526. CrossRef Medline
14. Cvekl A, Kashanchi F, Sax CM, Brady JN, Piatigorsky J (1995) Transcriptional regulation of the mouse alpha A-crystallin gene: activation dependent on a cyclic AMP-responsive element (DE1/CRE) and a Pax-6-binding site. Mol Cell Biol 15:653-660. Medline
15. D'Cruz PM, Yasumura D, Weir J, Matthes MT, Abderrahim H, LaVail MM, Vollrath D (2000) Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat. Hum Mol Genet 9:645-651. CrossRef Medline
16. de Oliveira RM (2006) Klotho RNAi induces premature senescence of human cells via a p53/p21 dependent pathway. FEBS Lett 580:5753-5758. CrossRef Medline
17. Economou MA, Wu J, Vasilcanu D, Rosengren L, All-Ericsson C, van der Ploeg I, Menu E, Girnita L, Axelson M, Larsson O, Seregard S, Kvanta A (2008) Inhibition of VEGF secretion and experimental choroidal neovascularization by picropodophyllin (PPP), an inhibitor of the insulinlike growth factor-1 receptor. Invest Ophthalmol Vis Sci 49:2620-2626. CrossRef Medline
18. Farinelli P, Arango-Gonzalez B, Volkl J, Alesutan I, Lang F, Zrenner E, Paquet-Durand F, Ekstrom PA (2013) Retinitis Pigmentosa: overexpression of anti-ageing protein Klotho in degenerating photoreceptors. J Neurochem. Advance online publication. doi:10.1111/jnc.12353. CrossRef Medline
19. Feeney-Burns L, Hilderbrand ES, Eldridge S (1984) Aging human RPE: morphometric analysis of macular, equatorial, and peripheral cells. Invest Ophthalmol Vis Sci 25:195-200. Medline
20. Feeney-Burns L, Gao CL, Tidwell M (1987) Lysosomal enzyme cytochemistry of human RPE, Bruch's membrane and drusen. Invest Ophthalmol Vis Sci 28:1138-1147. Medline
21. Gal A, Li Y, Thompson DA, Weir J, Orth U, Jacobson SG, Apfelstedt-Sylla E, Vollrath D (2000) Mutations in MERTK, the human orthologue of the RCS rat retinal dystrophy gene, cause retinitis pigmentosa. Nat Genet 26:270-271. CrossRef Medline
22. Gallicchio M, Mitola S, Valdembri D, Fantozzi R, Varnum B, Avanzi GC, Bussolino F (2005) Inhibition of vascular endothelial growth factor receptor 2-mediated endothelial cell activation by Axl tyrosine kinase receptor. Blood 105:1970-1976. CrossRef Medline
23. Gardner K, Bennett V (1986) A new erythrocyte membrane-associated protein with calmodulin binding activity. Identification and purification. J Biol Chem 261:1339-1348. Medline
24. Goding CR (2000) Mitf from neural crest to melanoma: signal transduction and transcription in the melanocyte lineage. Genes Dev 14:1712-1728. CrossRef Medline
25. Gregory CY, Abrams TA, Hall MO (1994) Stimulation of A2 adenosine receptors inhibits the ingestion of photoreceptor outer segments by retinal pigment epithelium. Invest Ophthalmol Vis Sci 35:819-825. Medline
26. Gu X, Neric NJ, Crabb JS, Crabb JW, Bhattacharya SK, Rayborn ME, Hollyfield JG, Bonilha VL (2012) Age-related changes in the retinal pigment epithelium (RPE). PLoS One 7:e38673. CrossRef Medline
27. Guo S, Rena G, Cichy S, He X, Cohen P, Unterman T (1999) Phosphorylation of serine 256 by protein kinase B disrupts transactivation by FKHR and mediates effects of insulin on insulin-like growth factor-binding protein-1 promoter activity through a conserved insulin response sequence. J Biol Chem 274:17184-17192. CrossRef Medline
28. Halaban R (2002) Pigmentation in melanomas: changes manifesting underlying oncogenic and metabolic activities. Oncol Res 13:3-8. Medline
29. Halaban R, Cheng E, Svedine S, Aron R, Hebert DN (2001) Proper folding and endoplasmic reticulum to golgi transport of tyrosinase are induced by its substrates, DOPA and tyrosine. J Biol Chem 276:11933-11938. CrossRef Medline
30. Hall MO, Abrams TA, Mittag TW (1993) The phagocytosis of rod outer segments is inhibited by drugs linked to cyclic adenosine monophosphate production. Invest Ophthalmol Vis Sci 34:2392-2401. Medline
31. Holtkamp GM, Van Rossem M, de Vos AF, Willekens B, Peek R, Kijlstra A (1998) Polarized secretion of IL-6 and IL-8 by human retinal pigment epithelial cells. Clin Exp Immunol 112:34-43. CrossRef Medline
32. Huang CL (2012) Regulation of ion channels by secreted Klotho. Adv Exp Med Biol 728:100-106. CrossRef Medline
33. Imai M, Ishikawa K, Matsukawa N, Kida I, Ohta J, Ikushima M, Chihara Y, Rui X, Rakugi H, Ogihara T (2004) Klotho protein activates the PKC pathway in the kidney and testis and suppresses 25-hydroxyvitamin D3 1alpha-hydroxylase gene expression. Endocrine 25:229-234. CrossRef Medline
34. Imura A, Tsuji Y, Murata M, Maeda R, Kubota K, Iwano A, Obuse C, Togashi K, Tominaga M, Kita N, Tomiyama K, Iijima J, Nabeshima Y, Fujioka M, Asato R, Tanaka S, Kojima K, Ito J, Nozaki K, Hashimoto N, et al (2007) alpha-Klotho as a regulator of calcium homeostasis. Science 316:1615-1618. CrossRef Medline
35. Kennedy BG, Torabi AJ, Kurzawa R, Echtenkamp SF, Mangini NJ (2010) Expression of transient receptor potential vanilloid channels TRPV5 and TRPV6 in retinal pigment epithelium. Mol Vis 16:665-675. Medline
36. Kevany BM, Palczewski K (2010) Phagocytosis of retinal rod and cone photoreceptors. Physiology (Bethesda) 25:8-15. CrossRef Medline
37. Klettner A, Westhues D, Lassen J, Bartsch S, Roider J (2013) Regulation of constitutive vascular endothelial growth factor secretion in retinal pigment epithelium/choroid organ cultures: p38, nuclear factor kappaB, and the vascular endothelial growth factor receptor-2/phosphatidylinositol 3 kinase pathway. Mol Vis 19:281-291. Medline
38. Kliffen M, Sharma HS, Mooy CM, Kerkvliet S, de Jong PT (1997) Increased expression of angiogenic growth factors in age-related maculopathy. Br J Ophthalmol 81:154-162. CrossRef Medline
39. Kokkinaki M, Sahibzada N, Golestaneh N (2011) Human iPS-derived retinal pigment epithelium (RPE) cells exhibit ion transport, membrane potential, polarized VEGF secretion and gene expression pattern similar to native RPE. Stem Cells 29:825-835. CrossRef Medline
40. Korshunov VA (2012) Axl-dependent signalling: a clinical update. Clin Sci (Lond) 122:361-368. CrossRef Medline
41. Kozlowski MR (2012) RPE cell senescence: a key contributor to age-related macular degeneration. Med Hypotheses 78:505-510. CrossRef Medline
42. Kuro-o M (2009) Klotho and aging. Biochim Biophys Acta 1790:1049-1058. CrossRef Medline
43. Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R, Nabeshima YI (1997) Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390:45-51. CrossRef Medline
44. Kurosu H, Yamamoto M, Clark JD, Pastor JV, Nandi A, Gurnani P, McGuinness OP, Chikuda H, Yamaguchi M, Kawaguchi H, Shimomura I, Takayama Y, Herz J, Kahn CR, Rosenblatt KP, Kuro-o M (2005) Suppression of aging in mice by the hormone Klotho. Science 309:1829-1833. CrossRef Medline
45. Kurz DJ, Decary S, Hong Y, Erusalimsky JD (2000) Senescence-associated (beta)-galactosidase reflects an increase in lysosomal mass during replicative ageing of human endothelial cells. J Cell Sci 113:3613-3622. Medline
46. Kusaba T, Okigaki M, Matui A, Murakami M, Ishikawa K, Kimura T, Sonomura K, Adachi Y, Shibuya M, Shirayama T, Tanda S, Hatta T, Sasaki S, Mori Y, Matsubara H (2010) Klotho is associated with VEGF receptor-2 and the transient receptor potential canonical-1 Ca2+ channel to maintain endothelial integrity. Proc Natl Acad Sci U S A 107: 19308-19313. CrossRef Medline
47. Lin H, Xu H, Liang FQ, Liang H, Gupta P, Havey AN, Boulton ME, Godley BF (2011) Mitochondrial DNA damage and repair in RPE associated with aging and age-related macular degeneration. Invest Ophthalmol Vis Sci 52:3521-3529. CrossRef Medline
48. Liu H, Fergusson MM, Castilho RM, Liu J, Cao L, Chen J, Malide D, Rovira II, Schimel D, Kuo CJ, Gutkind JS, Hwang PM, Finkel T (2007) Augmented Wnt signaling in a mammalian model of accelerated aging. Science 317:803-806. CrossRef Medline
49. Lu P, Boros S, Chang Q, Bindels RJ, Hoenderop JG (2008) The betaglucuronidase klotho exclusively activates the epithelial Ca2+ channels TRPV5 and TRPV6. Nephrol Dial Transplant 23:3397-3402. CrossRef Medline
50. Lu W, Gong D, Bar-Sagi D, Cole PA (2001) Site-specific incorporation of a phosphotyrosine mimetic reveals a role for tyrosine phosphorylation of SHP-2 in cell signaling. Mol Cell 8:759-769. CrossRef Medline
51. Maminishkis A, Chen S, Jalickee S, Banzon T, Shi G, Wang FE, Ehalt T, Hammer JA, Miller SS (2006) Confluent monolayers of cultured human fetal retinal pigment epithelium exhibit morphology and physiology of native tissue. Invest Ophthalmol Vis Sci 47:3612-3624. CrossRef Medline
52. Matsunaga H, Handa JT, Aotaki-Keen A, Sherwood SW, West MD, Hjelmeland LM (1999) Beta-galactosidase histochemistry and telomere loss in senescent retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 40: 197-202. Medline
53. Matsuoka Y, Hughes CA, Bennett V (1996) Adducin regulation. Definition of the calmodulin-binding domain and sites of phosphorylation by protein kinases A and C. J Biol Chem 271:25157-25166. CrossRef Medline
54. Montague W, Cook JR (1971) The role of adenosine 3:5-cyclic monophosphate in the regulation of insulin release by isolated rat islets of Langerhans. Biochem J 122:115-120. Medline
55. Nakae J, Park BC, Accili D (1999) Insulin stimulates phosphorylation of the forkhead transcription factor FKHR on serine 253 through a Wortmannin-sensitive pathway. J Biol Chem 274:15982-15985. CrossRef Medline
56. Negi A, Marmor MF (1984) Experimental serous retinal detachment and focal pigment epithelial damage. Arch Ophthalmol 102:445-449. CrossRef Medline
57. Nowak JZ (2006) Age-related macular degeneration (AMD): pathogenesis and therapy. Pharmacol Rep 58:353-363. Medline
58. Nunes P, Demaurex N (2010) The role of calcium signaling in phagocytosis. J Leukoc Biol 88:57-68. CrossRef Medline
59. Pierce KL, Premont RT, Lefkowitz RJ (2002) Seven-transmembrane receptors. Nat Rev Mol Cell Biol 3:639-650. CrossRef Medline
60. Rakugi H, Matsukawa N, Ishikawa K, Yang J, Imai M, Ikushima M, Maekawa Y, Kida I, Miyazaki J, Ogihara T (2007) Anti-oxidative effect of Klotho on endothelial cells through cAMP activation. Endocrine 31:82-87. CrossRef Medline
61. Reinisalo M, Putula J, Mannermaa E, Urtti A, Honkakoski P (2012) Regulation of the human tyrosinase gene in retinal pigment epithelium cells: the significance of transcription factor orthodenticle homeobox 2 and its polymorphic binding site. Mol Vis 18:38-54. Medline
62. Rena G, Guo S, Cichy SC, Unterman TG, Cohen P (1999) Phosphorylation of the transcription factor forkhead family member FKHR by protein kinase B. J Biol Chem 274:17179-17183. CrossRef Medline
63. Rosenthal R, Strauss O (2002) Ca2+-channels in the RPE. Adv Exp Med Biol 514:225-235. CrossRef Medline
64. Sarna T, Burke JM, Korytowski W, Rozanowska M, Skumatz CM, Zareba A, Zareba M (2003) Loss of melanin from human RPE with aging: possible role of melanin photooxidation. Exp Eye Res 76:89-98. CrossRef Medline
65. Schmidt SY, Peisch RD (1986) Melanin concentration in normal human retinal pigment epithelium. Regional variation and age-related reduction. Invest Ophthalmol Vis Sci 27:1063-1067. Medline
66. Schraermeyer U, Kopitz J, Peters S, Henke-Fahle S, Blitgen-Heinecke P, Kokkinou D, Schwarz T, Bartz-Schmidt KU (2006) Tyrosinase biosynthesis in adult mammalian retinal pigment epithelial cells. Exp Eye Res 83:315-321. CrossRef Medline
67. Seagle BL, Rezai KA, Kobori Y, Gasyna EM, Rezaei KA, Norris JR Jr (2005a) Melanin photoprotection in the human retinal pigment epithelium and its correlation with light-induced cell apoptosis. Proc Natl Acad SciU S A 102:8978-8983. CrossRef Medline
68. Seagle BL, Rezai KA, Gasyna EM, Kobori Y, Rezaei KA, Norris JR Jr (2005b) Time-resolved detection of melanin free radicals quenching reactive oxygen species. J Am Chem Soc 127:11220-11221. CrossRef Medline
69. Semba RD, Cappola AR, Sun K, Bandinelli S, Dalal M, Crasto C, Guralnik JM, Ferrucci L (2011) Plasma klotho and mortality risk in older communitydwelling adults. J Gerontol A Biol Sci Med Sci 66:794-800. CrossRef Medline
70. Shelton DN, Chang E, Whittier PS, Choi D, Funk WD (1999) Microarray analysis of replicative senescence. Curr Biol 9:939-945. CrossRef Medline
71. Slomiany MG, Rosenzweig SA (2004) IGF-1-induced VEGF and IGFBP-3 secretion correlates with increased HIF-1 alpha expression and activity in retinal pigment epithelial cell line D407. Invest Ophthalmol Vis Sci 45: 2838-2847. CrossRef Medline
72. Slominski A, Costantino R (1991a) Molecular mechanism of tyrosinase regulation by L-dopa in hamster melanoma cells. Life Sci 48:2075-2079. CrossRef Medline
73. Slominski A, Costantino R (1991b) L-tyrosine induces tyrosinase expression via a posttranscriptional mechanism. Experientia 47:721-724. CrossRef Medline
74. Slominski A, Moellmann G, Kuklinska E, Bomirski A, Pawelek J (1988) Positive regulation of melanin pigmentation by two key substrates of the melanogenic pathway, L-tyrosine and L-dopa. J Cell Sci 89:287-296. Medline
75. Slominski A, Moellmann G, Kuklinska E (1989a) L-tyrosine, L-dopa, and tyrosinase as positive regulators of the subcellular apparatus of melanogenesis in Bomirski Ab amelanotic melanoma cells. Pigment Cell Res 2:109-116. CrossRef Medline
76. Slominski A, Jastreboff P, Pawelek J (1989b) L-tyrosine stimulates induction of tyrosinase activity by MSH and reduces cooperative interactions between MSH receptors in hamster melanoma cells. Biosci Rep 9:579-586. CrossRef Medline
77. Slominski A, Tobin DJ, Shibahara S, Wortsman J (2004) Melanin pigmentation in mammalian skin and its hormonal regulation. Physiol Rev 84: 1155-1228. CrossRef Medline
78. + ATPase by Klotho. FEBS Lett 585:1759-1764. CrossRef Medline
79. Strauss O (2005) The retinal pigment epithelium in visual function. Physiol Rev 85:845-881. CrossRef Medline
80. Sun K, Cai H, Tezel TH, Paik D, Gaillard ER, Del Priore LV (2007) Bruch's membrane aging decreases phagocytosis of outer segments by retinal pigment epithelium. Mol Vis 13:2310-2319. Medline
81. Sundelin S, Wihlmark U, Nilsson SE, Brunk UT (1998) Lipofuscin accumulation in cultured retinal pigment epithelial cells reduces their phagocytic capacity. Curr Eye Res 17:851-857. CrossRef Medline
82. Tassabehji M, Newton VE, Read AP (1994) Waardenburg syndrome type 2 caused by mutations in the human microphthalmia (MITF) gene. Nat Genet 8:251-255. CrossRef Medline
83. Wan P, Hu Y, He L (2011) Regulation of melanocyte pivotal transcription factor MITF by some other transcription factors. Mol Cell Biochem 354: 241-246. CrossRef Medline
84. Wang J, Ohno-Matsui K, Morita I (2012a) Elevated amyloid beta production in senescent retinal pigment epithelium, a possible mechanism of subretinal deposition of amyloid beta in age-related macular degeneration. Biochem Biophys Res Commun 423:73-78. CrossRef Medline
85. Wang N, Hebert DN (2006) Tyrosinase maturation through the mammalian secretory pathway: bringing color to life. Pigment Cell Res 19:3-18. CrossRef Medline
86. Wang Y, Kuro-o M, Sun Z (2012b) Klotho gene delivery suppresses Nox2 expression and attenuates oxidative stress in rat aortic smooth muscle cells via the cAMP-PKA pathway. Aging Cell 11:410-417. CrossRef Medline
87. Wang Z, Dillon J, Gaillard ER (2006) Antioxidant properties of melanin in retinal pigment epithelial cells. Photochem Photobiol 82:474-479. CrossRef Medline
88. Weiter JJ, Delori FC, Wing GL, Fitch KA (1986) Retinal pigment epithelial lipofuscin and melanin and choroidal melanin in human eyes. Invest Ophthalmol Vis Sci 27:145-152. Medline
89. Widlund HR, Fisher DE (2003) Microphthalamia-associated transcription factor: a critical regulator of pigment cell development and survival. Oncogene 22:3035-3041. CrossRef Medline
90. Wolf I, Levanon-Cohen S, Bose S, Ligumsky H, Sredni B, Kanety H, Kuro-o M, Karlan B, Kaufman B, Koeffler HP, Rubinek T (2008) Klotho: a tumor suppressor and a modulator of the IGF-1 and FGF pathways in human breast cancer. Oncogene 27:7094-7105. CrossRef Medline
91. Yamamoto M, Clark JD, Pastor JV, Gurnani P, Nandi A, Kurosu H, Miyoshi M, Ogawa Y, Castrillon DH, Rosenblatt KP, Kuro-o M (2005) Regulation of oxidative stress by the anti-aging hormone klotho. J Biol Chem 280:38029-38034. CrossRef Medline
92. Yamazaki Y, Imura A, Urakawa I, Shimada T, Murakami J, Aono Y, Hasegawa H, Yamashita T, Nakatani K, Saito Y, Okamoto N, Kurumatani N, Namba N, Kitaoka T, Ozono K, Sakai T, Hataya H, Ichikawa S, Imel EA, Econs MJ, et al. (2010) Establishment of sandwich ELISA for soluble alpha- Klotho measurement: age-dependent change of soluble alpha-Klotho levels in healthy subjects. Biochem Biophys Res Commun 398:513-518. CrossRef Medline
93. Yang J, Matsukawa N, Rakugi H, Imai M, Kida I, Nagai M, Ohta J, Fukuo K, Nabeshima Y, Ogihara T (2003) Upregulation of cAMP is a new functional signal pathway of Klotho in endothelial cells. Biochem Biophys Res Commun 301:424-429. CrossRef Medline
94. Yin D (1996) Biochemical basis of lipofuscin, ceroid, and age pigment-like fluorophores. Free Radic Biol Med 21:871-888. CrossRef Medline
95. Zhang L, Insel PA (2001) Bcl-2 protects lymphoma cells from apoptosis but not growth arrest promoted by cAMP and dexamethasone. Am J Physiol Cell Physiol 281:C1642-C1647. Medline