Hypoxia-induced adrenomedullin production in the kidney

Nagata, Daisuke; Hirata, Yasunobu; Suzuki, Emiko; Kakoki, Masao; Hayakawa, Hiroshi; Goto, Atsuo; Ishimitsu, Toshihiko; Minamino, Naoto; Ono, Yukari; Kangawa, Kenji; Matsuo, Hisayuki; Omata, Masao

doi:10.1046/j.1523-1755.1999.00361.x

Cited by 80 publications

(53 citation statements)

References 34 publications

(8 reference statements)

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“…After a 1-day incubation in low mitogen media, transduced cells were placed in a hypoxia chamber (GasPak anaerobic system; BD Biosciences) according to the manufacturer's instructions for the indicated period of time. This system induces anaerobic conditions of less than 2% of oxygen and more than 4% of carbon dioxide by using carbon dioxidegenerating reagents (34). All experiments utilized HUVECs at passage 6 or less.…”

Section: Methodsmentioning

confidence: 99%

AMP-activated Protein Kinase (AMPK) Signaling in Endothelial Cells Is Essential for Angiogenesis in Response to Hypoxic Stress

Nagata¹,

Mogi

Walsh

2003

Journal of Biological Chemistry

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319

338

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AMP-activated protein kinase (AMPK) is a stress-activated protein kinase that is regulated by hypoxia and other cellular stresses that result in diminished cellular ATP levels. Here, we investigated whether AMPK signaling in endothelial cells has a role in regulating angiogenesis. Hypoxia induced the activating phosphorylation of AMPK in human umbilical vein endothelial cells (HUVECs), and AMPK activation was required for the maintenance of pro-angiogenic Akt signaling under these conditions. Suppression of AMPK signaling inhibited both HUVEC migration to VEGF and in vitro differentiation into tube-like structures in hypoxic, but not normoxic cultures. Dominant-negative AMPK also inhibited in vivo angiogenesis in Matrigel plugs that were implanted subcutaneously in mice. These data identify AMPK signaling as a new regulator of angiogenesis that is specifically required for endothelial cell migration and differentiation under conditions of hypoxia. As such, endothelial AMPK signaling may be a critical determinant of blood vessel recruitment to tissues that are subjected to ischemic stress.Angiogenesis is central feature of normal embryonic and post-natal development, and this process plays a critical role in the neovascularization that is associated with tumor growth and occlusive vascular diseases (1-3). A large body of evidence has shown that vascular angiogenic growth factors promote angiogenesis through activation of MAP kinase (4) and phosphatidylinositol 3-kinase (PI3K)-Akt/PKB (5) intracellular signaling pathways. However, the signaling molecules involved in angiogenic cellular responses under conditions of hypoxic stress is incompletely understood.AMP-activated protein kinase (AMPK) 1 is a metabolite-sensing protein kinase that shares amino acid sequence homology with yeast SNF1 (6, 7). In myocytes, AMPK is activated by increases in the AMP:ATP ratio, which is brought about by hypoxia/anoxia (8 -10), vigorous exercise and muscle contraction (11-14) or pressure-overload hypertrophy (15). Under these conditions, AMPK is activated by a conformational change after binding AMP (16,17), and by phosphorylation by its upstream kinase AMPK kinase (AMPKK) (17-19). Upon activation, AMPK phosphorylates and down-regulates several anabolic enzymes including 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase (16,20), acetyl-CoA carboxylase (ACC) (16, 21), sn-glycerol-3-phosphate acetyltransferase (22, 23), and glycogen synthase (24); thereby diminishing metabolite flux through synthetic pathways that consume ATP. AMPK activation also accelerates ␤-oxidation of fatty acid, which promotes ATP production (25, 26).Endothelial nitric-oxide synthase (eNOS) residue 1177 (in human) is a substrate for both Akt (27, 28) and AMPK (29). Phosphorylation of eNOS at this residue leads to enzyme activation and nitric oxide (NO) production. AMPK is reported to phosphorylate eNOS in cardiac myocytes under hypoxic conditions (29), but it is not clear whether NO production by endothelial cells is regulated by this reaction. Recently, AMPK ...

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Section: Methodsmentioning

confidence: 99%

AMP-activated Protein Kinase (AMPK) Signaling in Endothelial Cells Is Essential for Angiogenesis in Response to Hypoxic Stress

Nagata¹,

Mogi

Walsh

2003

Journal of Biological Chemistry

Self Cite

319

338

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“…Assessment of mRNA Stability-Effects of t-RA on the stability of MKP-1 mRNA were assessed using the RNA synthesis inhibitor actinomycin D (39). In brief, mesangial cells were treated with or without t-RA (1 M) for 1 h in the presence of actinomycin D (5 g/ml; Serva, Heidelberg, Germany) for the last 0 -60 min.…”

Section: Methodsmentioning

confidence: 99%

Transcriptional Induction of Mitogen-activated Protein Kinase Phosphatase 1 by Retinoids

Xu¹,

Konta²,

Furusu³

et al. 2002

Journal of Biological Chemistry

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“…22 The cells migrating from male Wistar rat (8-week-old) aortas fragments were subcultured and expanded in Dulbecco's modied Eagle's medium with 10% fetal bovine serum, 100 U ml À1 penicillin and 100 mg ml À1 streptomycin. All experiments utilized VSMCs at passage 6 or less.…”

Section: Cell Culturementioning

confidence: 99%

Aldosterone-induced osteopontin gene transcription in vascular smooth muscle cells involves glucocorticoid response element

et al. 2011

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Osteopontin (OPN) is known to be one of the cytokines that is involved in the vascular inflammation caused by aldosterone (Aldo). Previous reports have shown that Aldo increases OPN transcripts, and the mechanisms for this remain to be clarified. In this study, we investigated how Aldo increases OPN transcripts in the vascular smooth muscle cells of rats. Aldosterone increased OPN transcripts time-dependently as well as dose-dependently. This increase was diminished by eplerenone, a mineralocorticoid receptor (MR) antagonist. Luciferase promoter assays showed that the OPN promoter deleted to the À1599 site retained the same promoting ability as the full-length OPN promoter when stimulated by 10 À7 M Aldo, but the promoter deleted to the À1300 site lost the promoting ability. A glucocorticoid response element (GRE) is located in that deleted region. Luciferase assays of a mutated promoter without the GRE lost the luciferase upregulation, although mutated promoters with the deletion of other consensus sites maintained the promoter activity. The binding of the Aldo-MR complex to the GRE fragment was confirmed by an electrophoretic-mobility shift assay. This is the first report showing that Aldo regulates the transcriptional levels of OPN and inflammatory responses in the vasculature through a specific GRE site in the OPN promoter region.

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Hypoxia-induced adrenomedullin production in the kidney

Abstract: Renal parenchymal cells as well as renal vessels may produce AM under hypoxic conditions.

Cited by 80 publications

References 34 publications

AMP-activated Protein Kinase (AMPK) Signaling in Endothelial Cells Is Essential for Angiogenesis in Response to Hypoxic Stress

AMP-activated Protein Kinase (AMPK) Signaling in Endothelial Cells Is Essential for Angiogenesis in Response to Hypoxic Stress

Transcriptional Induction of Mitogen-activated Protein Kinase Phosphatase 1 by Retinoids

Aldosterone-induced osteopontin gene transcription in vascular smooth muscle cells involves glucocorticoid response element

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