help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kato, H.
Right arrow Articles by Hirata, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kato, H.
Right arrow Articles by Hirata, Y.
Endocrinology Vol. 138, No. 6 2615-2620
Copyright © 1997 by The Endocrine Society

ARTICLES

Adrenomedullin as an Autocrine/Paracrine Apoptosis Survival Factor for Rat Endothelial Cells1

Hiroki Kato, Masayoshi Shichiri, Fumiaki Marumo and Yukio Hirata

Endocrine-Hypertension Division, Second Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo 113, Japan

Address all correspondence and requests for reprints to: Masayoshi Shichiri, M.D., Second Department of Internal Medicine, Tokyo Medical and Dental University, Yushima 1–5-45, Bunkyo-ku, Tokyo 113, Japan. (Masayoshi Shichiri). E-mail address: mshichiri.med2{at}med.tmd.ac.jp

Adrenomedullin is a potent vasorelaxant/hypotensive peptide recently isolated from human pheochromocytoma. We demonstrate here a novel role of this peptide as an apoptosis survival factor for rat endothelial cells. When rendered quiescent by serum deprivation, a fraction of endothelial cell cultures showed morphological and biochemical features characteristic of apoptosis. Adrenomedullin significantly suppressed apoptosis without inducing cell proliferation. Rat endothelial cells that contained high affinity binding sites for adrenomedullin expressed adrenomedullin gene and released the peptide into culture media. Addition of preimmune rabbit serum prevented apoptosis, whereas rabbit antiadrenomedullin antiserum partially, but significantly, abrogated the protective effect of the preimmune serum, suggesting its autocrine/paracrine role. Although adrenomedullin induced intracellular cAMP formation, other cAMP-elevating agonists, such as prostaglandin I2 and forskolin, did not affect apoptosis. Furthermore, adenosine 3',5'-cyclicmonophosphothioate Rp-isomer, a cAMP antagonist, did not block the cell survival effect of adrenomedullin. Adrenomedullin neither increased intracellular Ca2+ concentrations nor inositol-1,4,5-trisphosphate levels in rat endothelial cells. These results demonstrate that adrenomedullin suppresses serum deprivation-induced apoptosis of rat endothelial cells via cAMP-independent mechanism.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
H. N. Woodward, A. Anwar, S. Riddle, L. Taraseviciene-Stewart, M. Fragoso, K. R. Stenmark, and E. V. Gerasimovskaya
PI3K, Rho, and ROCK play a key role in hypoxia-induced ATP release and ATP-stimulated angiogenic responses in pulmonary artery vasa vasorum endothelial cells
Am J Physiol Lung Cell Mol Physiol, November 1, 2009; 297(5): L954 - L964.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
R. Norregaard, T. Bodker, B. L. Jensen, L. Stodkilde, S. Nielsen, and J. Frokiaer
Increased renal adrenomedullin expression in rats with ureteral obstruction
Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2009; 296(1): R185 - R192.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Miksa, R. Wu, X. Cui, W. Dong, P. Das, H. H. Simms, T. S. Ravikumar, and P. Wang
Vasoactive Hormone Adrenomedullin and Its Binding Protein: Anti-Inflammatory Effects by Up-Regulating Peroxisome Proliferator-Activated Receptor-{gamma}
J. Immunol., November 1, 2007; 179(9): 6263 - 6272.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
T. Itoh, H. Obata, S. Murakami, K. Hamada, K. Kangawa, H. Kimura, and N. Nagaya
Adrenomedullin ameliorates lipopolysaccharide-induced acute lung injury in rats
Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L446 - L452.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Pathol.Home page
M. Nowicki, D. Ostalska-Nowicka, B. Kondraciuk, and B. Miskowiak
The significance of substance P in physiological and malignant haematopoiesis
J. Clin. Pathol., July 1, 2007; 60(7): 749 - 755.
[Abstract] [Full Text] [PDF]

Home page
 Poult. Sci.Home page
A. P. Gomez, M. J. Moreno, A. Iglesias, P. X. Coral, and A. Hernandez
Endothelin 1, its Endothelin Type A Receptor, Connective Tissue Growth Factor, Platelet-Derived Growth Factor, and Adrenomedullin Expression in Lungs of Pulmonary Hypertensive and Nonhypertensive Chickens
Poult. Sci., May 1, 2007; 86(5): 909 - 916.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
V. Ramachandran, T. Arumugam, R. F. Hwang, J. K. Greenson, D. M. Simeone, and C. D. Logsdon
Adrenomedullin Is Expressed in Pancreatic Cancer and Stimulates Cell Proliferation and Invasion in an Autocrine Manner via the Adrenomedullin Receptor, ADMR
Cancer Res., March 15, 2007; 67(6): 2666 - 2675.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
Q. Xu, N. Ohara, W. Chen, J. Liu, H. Sasaki, A. Morikawa, R. Sitruk-Ware, E. D.B. Johansson, and T. Maruo
Progesterone receptor modulator CDB-2914 down-regulates vascular endothelial growth factor, adrenomedullin and their receptors and modulates progesterone receptor content in cultured human uterine leiomyoma cells
Hum. Reprod., September 1, 2006; 21(9): 2408 - 2416.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
B. Uzan, H.-K. Ea, J.-M. Launay, J.-M. Garel, R. Champy, M. Cressent, and F. Liote
A Critical Role for Adrenomedullin-Calcitonin Receptor-Like Receptor in Regulating Rheumatoid Fibroblast-Like Synoviocyte Apoptosis
J. Immunol., May 1, 2006; 176(9): 5548 - 5558.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
L. L. Nikitenko, N. Blucher, S. B. Fox, R. Bicknell, D. M. Smith, and M. C. P. Rees
Adrenomedullin and CGRP interact with endogenous calcitonin-receptor-like receptor in endothelial cells and induce its desensitisation by different mechanisms.
J. Cell Sci., March 1, 2006; 119(Pt 5): 910 - 922.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
H Watanabe, E Takahashi, M Kobayashi, M Goto, A Krust, P Chambon, and T Iguchi
The estrogen-responsive adrenomedullin and receptor-modifying protein 3 gene identified by DNA microarray analysis are directly regulated by estrogen receptor
J. Mol. Endocrinol., February 1, 2006; 36(1): 81 - 89.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
J. Kato, T. Tsuruda, T. Kita, K. Kitamura, and T. Eto
Adrenomedullin: A Protective Factor for Blood Vessels
Arterioscler Thromb Vasc Biol, December 1, 2005; 25(12): 2480 - 2487.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
X. Zhang, K. E. Green, C. Yallampalli, and Y. L. Dong
Adrenomedullin Enhances Invasion by Trophoblast Cell Lines
Biol Reprod, October 1, 2005; 73(4): 619 - 626.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
S. Murakami, N. Nagaya, T. Itoh, T. Iwase, T. Fujisato, K. Nishioka, K. Hamada, K. Kangawa, and H. Kimura
Adrenomedullin Regenerates Alveoli and Vasculature in Elastase-induced Pulmonary Emphysema in Mice
Am. J. Respir. Crit. Care Med., September 1, 2005; 172(5): 581 - 589.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Frede, P. Freitag, T. Otto, C. Heilmaier, and J. Fandrey
The Proinflammatory Cytokine Interleukin 1{beta} and Hypoxia Cooperatively Induce the Expression of Adrenomedullin in Ovarian Carcinoma Cells through Hypoxia Inducible Factor 1 Activation
Cancer Res., June 1, 2005; 65(11): 4690 - 4697.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
N. Nagaya, H. Mori, S. Murakami, K. Kangawa, and S. Kitamura
Adrenomedullin: angiogenesis and gene therapy
Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2005; 288(6): R1432 - R1437.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
K. Hanabusa, N. Nagaya, T. Iwase, T. Itoh, S. Murakami, Y. Shimizu, W. Taki, K. Miyatake, and K. Kangawa
Adrenomedullin Enhances Therapeutic Potency of Mesenchymal Stem Cells After Experimental Stroke in Rats
Stroke, April 1, 2005; 36(4): 853 - 858.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
N. Fukai, T. Yoshimoto, T. Sugiyama, N. Ozawa, R. Sato, M. Shichiri, and Y. Hirata
Concomitant expression of adrenomedullin and its receptor components in rat adipose tissues
Am J Physiol Endocrinol Metab, January 1, 2005; 288(1): E56 - E62.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
J. Penchalaneni, S. J. Wimalawansa, and C. Yallampalli
Adrenomedullin Antagonist Treatment During Early Gestation in Rats Causes Fetoplacental Growth Restriction Through Apoptosis
Biol Reprod, November 1, 2004; 71(5): 1475 - 1483.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
N. Ozawa, M. Shichiri, N. Fukai, T. Yoshimoto, and Y. Hirata
Regulation of Adrenomedullin Gene Transcription and Degradation by the c-myc Gene
Endocrinology, September 1, 2004; 145(9): 4244 - 4250.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
T. Yoshimoto, N. Fukai, R. Sato, T. Sugiyama, N. Ozawa, M. Shichiri, and Y. Hirata
Antioxidant Effect of Adrenomedullin on Angiotensin II-Induced Reactive Oxygen Species Generation in Vascular Smooth Muscle Cells
Endocrinology, July 1, 2004; 145(7): 3331 - 3337.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
P. Sandner, K. H. Hofbauer, H. Tinel, A. Kurtz, H. C. Thiesson, P. D. Ottosen, S. Walter, O. Skott, and B. L. Jensen
Expression of adrenomedullin in hypoxic and ischemic rat kidneys and human kidneys with arterial stenosis
Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2004; 286(5): R942 - R951.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
N. Tokunaga, N. Nagaya, M. Shirai, E. Tanaka, H. Ishibashi-Ueda, M. Harada-Shiba, M. Kanda, T. Ito, W. Shimizu, Y. Tabata, et al.
Adrenomedullin Gene Transfer Induces Therapeutic Angiogenesis in a Rabbit Model of Chronic Hind Limb Ischemia: Benefits of a Novel Nonviral Vector, Gelatin
Circulation, February 3, 2004; 109(4): 526 - 531.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
H. Okumura, N. Nagaya, T. Itoh, I. Okano, J. Hino, K. Mori, Y. Tsukamoto, H. Ishibashi-Ueda, S. Miwa, K. Tambara, et al.
Adrenomedullin Infusion Attenuates Myocardial Ischemia/Reperfusion Injury Through the Phosphatidylinositol 3-Kinase/Akt-Dependent Pathway
Circulation, January 20, 2004; 109(2): 242 - 248.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
N. Fukai, M. Shichiri, N. Ozawa, M. Matsushita, and Y. Hirata
Coexpression of Calcitonin Receptor-Like Receptor and Receptor Activity-Modifying Protein 2 or 3 Mediates the Antimigratory Effect of Adrenomedullin
Endocrinology, February 1, 2003; 144(2): 447 - 453.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
A. Martinez, M. Vos, L. Guedez, G. Kaur, Z. Chen, M. Garayoa, R. Pio, T. Moody, W. G. Stetler-Stevenson, H. K. Kleinman, et al.
The Effects of Adrenomedullin Overexpression in Breast Tumor Cells
J Natl Cancer Inst, August 21, 2002; 94(16): 1226 - 1237.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
Y. Imai, T. Shindo, K. Maemura, M. Sata, Y. Saito, Y. Kurihara, M. Akishita, J. Osuga, S. Ishibashi, K. Tobe, et al.
Resistance to Neointimal Hyperplasia and Fatty Streak Formation in Mice With Adrenomedullin Overexpression
Arterioscler Thromb Vasc Biol, August 1, 2002; 22(8): 1310 - 1315.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
T. Tsuruda and J. C. Burnett Jr
Adrenomedullin: An Autocrine/Paracrine Factor for Cardiorenal Protection
Circ. Res., April 5, 2002; 90(6): 625 - 627.
[Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
L'H. Ouafik, S. Sauze, F. Boudouresque, O. Chinot, C. Delfino, F. Fina, V. Vuaroqueaux, C. Dussert, J. Palmari, H. Dufour, et al.
Neutralization of Adrenomedullin Inhibits the Growth of Human Glioblastoma Cell Lines in Vitro and Suppresses Tumor Xenograft Growth in Vivo
Am. J. Pathol., April 1, 2002; 160(4): 1279 - 1292.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
G. S. Filippatos, N. Gangopadhyay, O. Lalude, N. Parameswaran, S. I. Said, W. Spielman, and B. D. Uhal
Regulation of apoptosis by vasoactive peptides
Am J Physiol Lung Cell Mol Physiol, October 1, 2001; 281(4): L749 - L761.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
T. Moriyama, T. Otani, and T. Maruo
Expression of Adrenomedullin by Human Placental Cytotrophoblasts and Choriocarcinoma JAr Cells
J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3958 - 3961.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
B. C. Berk
Vascular Smooth Muscle Growth: Autocrine Growth Mechanisms
Physiol Rev, July 1, 2001; 81(3): 999 - 1030.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
T. Udono, K. Takahashi, M. Nakayama, A. Yoshinoya, K. Totsune, O. Murakami, Y. K. Durlu, M. Tamai, and S. Shibahara
Induction of Adrenomedullin by Hypoxia in Cultured Retinal Pigment Epithelial Cells
Invest. Ophthalmol. Vis. Sci., April 1, 2001; 42(5): 1080 - 1086.
[Abstract] [Full Text]

Home page
 FASEB J.Home page
M. SHICHIRI and Y. HIRATA
Antiangiogenesis signals by endostatin
FASEB J, April 1, 2001; 15(6): 1044 - 1053.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
P. Rocchi, F. Boudouresque, A. J. Zamora, X. Muracciole, E. Lechevallier, P.-M. Martin, and L'H. Ouafik
Expression of Adrenomedullin and Peptide Amidation Activity in Human Prostate Cancer and in Human Prostate Cancer Cell Lines
Cancer Res., February 1, 2001; 61(3): 1196 - 1206.
[Abstract] [Full Text]

Home page
 HypertensionHome page
M. Sata, M. Kakoki, D. Nagata, H. Nishimatsu, E. Suzuki, T. Aoyagi, S. Sugiura, H. Kojima, T. Nagano, K. Kangawa, et al.
Adrenomedullin and Nitric Oxide Inhibit Human Endothelial Cell Apoptosis via a Cyclic GMP-Independent Mechanism
Hypertension, July 1, 2000; 36(1): 83 - 88.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
M. Garayoa, A. Martínez, S. Lee, R. Pío, W. G. An, L. Neckers, J. Trepel, L. M. Montuenga, H. Ryan, R. Johnson, et al.
Hypoxia-Inducible Factor-1 (HIF-1) Up-Regulates Adrenomedullin Expression in Human Tumor Cell Lines during Oxygen Deprivation: A Possible Promotion Mechanism of Carcinogenesis
Mol. Endocrinol., June 1, 2000; 14(6): 848 - 862.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
P. G. Andreis, A. Markowska, H. C. Champion, G. Mazzocchi, L. K. Malendowicz, and G. G. Nussdorfer
Adrenomedullin Enhances Cell Proliferation and Deoxyribonucleic Acid Synthesis in Rat Adrenal Zona Glomerulosa: Receptor Subtype Involved and Signaling Mechanism
Endocrinology, June 1, 2000; 141(6): 2098 - 2104.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
J. P. Hinson, S. Kapas, and D. M. Smith
Adrenomedullin, a Multifunctional Regulatory Peptide
Endocr. Rev., April 1, 2000; 21(2): 138 - 167.
[Abstract] [Full Text]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
M. Shichiri, M. Yokokura, F. Marumo, and Y. Hirata
Endothelin-1 Inhibits Apoptosis of Vascular Smooth Muscle Cells Induced by Nitric Oxide and Serum Deprivation via MAP Kinase Pathway
Arterioscler Thromb Vasc Biol, April 1, 2000; 20(4): 989 - 997.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
T. Stefanec
Endothelial Apoptosis: Could It Have a Role in the Pathogenesis and Treatment of Disease?
Chest, March 1, 2000; 117(3): 841 - 854.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
K. Shimizu, H. Tanaka, M. Sunamori, F. Marumo, and M. Shichiri
Adrenomedullin Receptor Antagonism by Calcitonin Gene-Related Peptide(8-37) Inhibits Carotid Artery Neointimal Hyperplasia After Balloon Injury
Circ. Res., December 3, 1999; 85(12): 1199 - 1205.
[Abstract] [Full Text] [PDF]

Home page
 J. Histochem. Cytochem.Home page
N. Jiménez, A. Calvo, A. Martínez, D. Rosell, F. Cuttitta, and L. M. Montuenga
Expression of Adrenomedullin and Proadrenomedullin N-terminal 20 Peptide in Human and Rat Prostate
J. Histochem. Cytochem., September 1, 1999; 47(9): 1167 - 1178.
[Abstract] [Full Text]

Home page
 Mol. Endocrinol.Home page
M. Shichiri, H. Kato, M. Doi, F. Marumo, and Y. Hirata
Induction of Max by Adrenomedullin and Calcitonin Gene-Related Peptide Antagonizes Endothelial Apoptosis
Mol. Endocrinol., August 1, 1999; 13(8): 1353 - 1363.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
E. B. Pewitt, R. Haleem, and Z. Wang
Adrenomedullin Gene Is Abundantly Expressed and Directly Regulated by Androgen in the Rat Ventral Prostate
Endocrinology, May 1, 1999; 140(5): 2382 - 2386.
[Abstract] [Full Text]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
N. Suenobu, M. Shichiri, M. Iwashina, F. Marumo, and Y. Hirata
Natriuretic Peptides and Nitric Oxide Induce Endothelial Apoptosis via a cGMP–Dependent Mechanism
Arterioscler Thromb Vasc Biol, January 1, 1999; 19(1): 140 - 146.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
T. Horio, T. Nishikimi, F. Yoshihara, N. Nagaya, H. Matsuo, S. Takishita, and K. Kangawa
Production and Secretion of Adrenomedullin in Cultured Rat Cardiac Myocytes and Nonmyocytes: Stimulation by Interleukin-1{beta} and Tumor Necrosis Factor-{alpha}
Endocrinology, November 1, 1998; 139(11): 4576 - 4580.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
M. Shichiri, J. M. Sedivy, F. Marumo, and Y. Hirata
Endothelin-1 Is a Potent Survival Factor for c-Myc-Dependent Apoptosis
Mol. Endocrinol., February 1, 1998; 12(2): 172 - 180.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
M. Shichiri, S. Adachi, J. M. Sedivy, F. Marumo, and Y. Hirata
Biphasic Regulation of the Preproendothelin-1 Gene by c-myc
Endocrinology, November 1, 1997; 138(11): 4584 - 4590.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
M. Shichiri, H. Kato, F. Marumo, and Y. Hirata
Endothelin-1 as an Autocrine/Paracrine Apoptosis Survival Factor for Endothelial Cells
Hypertension, November 1, 1997; 30(5): 1198 - 1203.
[Abstract] [Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1997 by The Endocrine Society