Myogenic Akt Signaling Regulates Blood Vessel Recruitment during Myofiber Growth

Takahashi, Akihiro; Kureishi, Yasuko; Jiang, Yang; Luo, Zhengyu; Guo, Kun; Mukhopadhyay, Debabrata; Ivashchenko, Yuri; Branellec, Didier; Walsh, Kenneth

doi:10.1128/mcb.22.13.4803-4814.2002

Cited by 150 publications

(151 citation statements)

References 69 publications

Supporting

Mentioning

134

Contrasting

Unclassified

Order By: Relevance

“…Transduction with dominant-negative Akt also inhibited capillary formation in Matrigel plugs implanted in mice. While a number of studies have shown that constitutive activation of Akt signaling is sufficient to promote angiogenesis in vivo (37,56,57), the data presented here provide the first direct evidence showing that Akt signaling is essential for neovascularization in an animal model.…”

Section: Ampk Regulates Capillary Formation In Matrigel Plugs In Vivo-mentioning

confidence: 71%

“…Stimuli that may activate endothelial AMPK in vivo include decreases in oxygen tension that are associated with tumor growth or occlusive vessel diseases (29,59). In contrast, angiogenesis associated with normal tissue growth and organ enlargement during development can be subject to regulatory controls that function independently of tissue oxygen gradients (56,60). Collectively, these data suggest endothelial AMPK signaling may be an essential feature of the angiogenic response to ischemic stress, while having minimal effects on angiogenic endothelial cell responses during FIG.…”

Section: Ampk Regulates Capillary Formation In Matrigel Plugs In Vivo-mentioning

confidence: 83%

See 1 more Smart Citation

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

320

338

View full text Add to dashboard Cite

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 ...

show abstract

Section: Ampk Regulates Capillary Formation In Matrigel Plugs In Vivo-mentioning

confidence: 71%

Section: Ampk Regulates Capillary Formation In Matrigel Plugs In Vivo-mentioning

confidence: 83%

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

320

338

View full text Add to dashboard Cite

show abstract

“…It is also recognized that skeletal muscle hypertrophy is coupled to angiogenesis, through molecular mechanisms that are independent of tissue hypoxia (6). VEGF, a strong stimulator of angiogenesis, is up-regulated during myofiber hypertrophy by myogenic Akt signaling.…”

Section: Discussionmentioning

confidence: 99%

“…The expression of constitutively active Akt1 in skeletal muscle stimulates muscle hypertrophy both in vitro and in vivo (6 -9). Adenovirus-mediated transduction of constitutively active Akt1 also promotes the induction of the vascular endothelial growth factor (VEGF), 3 and this is accompanied by an increase in limb perfusion and capillary density in muscles where Akt1 is overexpressed (6). Constitutive activation of Akt1 in the heart also promotes myocardial angiogenesis, which is partly mediated by the induction of VEGF (10,11).…”

mentioning

confidence: 99%

Follistatin-like 1, a Secreted Muscle Protein, Promotes Endothelial Cell Function and Revascularization in Ischemic Tissue through a Nitric-oxide Synthase-dependent Mechanism

Ouchi

Oshima²,

Ohashi

et al. 2008

Journal of Biological Chemistry

Self Cite

273

249

View full text Add to dashboard Cite

show abstract

“…Therefore, PI3K activity is necessary for IGF-1 to induce hypertrophy, and its activation is sufficient to induce hypertrophy. Expression of an activated form of Akt1 in skeletal muscle cells is sufficient to induce hypertrophy [33,36,37]. Downregulation of the Akt pathway has been observed in skeletal muscle atrophy [20].…”

Section: Heart Failure and Angiotensin IImentioning

confidence: 99%

Angiotensin II as candidate of cardiac cachexia

Delafontaine

Akao

2006

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

View full text Add to dashboard Cite

Purpose of review-Congestive heart failure is increasing in prevalence and represents a major public health problem. The syndrome of advanced heart failure often includes muscle wasting, commonly termed cardiac cachexia, which is a predictor of poor outcome. Mechanisms of cardiac cachexia are poorly understood, but there is recent evidence that increased angiotensin II, interacting with the insulin-like growth factor-1 system, plays an important role.Recent findings-In animals, angiotensin II produces weight loss through a pressorindependent mechanism, accompanied by decreased levels of circulating and skeletal muscle insulin-like growth factor-1 and increased mRNA levels of the ubiquitin ligases atrogin-1 and Muscle RING finger-1 in skeletal muscle. Reduced insulin-like growth factor-1 action in muscle leads to increased proteolysis, through the ubiquitin-proteasome pathway, and increased apoptosis. These changes are blocked by muscle-specific expression of insulin-like growth factor-1, likely to be via the Akt/mTOR/p70S6K signaling pathway.Summary-The link between insulin-like growth factor-1, the ubiquitin-proteasome pathway, and angiotensin II effects has widespread clinical implications for the understanding of mechanisms of catabolic conditions. Therapeutic interventions targeting cross-talk mechanisms between angiotensin II and insulin-like growth factor-1 effects could provide new approaches for the treatment of muscle wasting.

show abstract

Myogenic Akt Signaling Regulates Blood Vessel Recruitment during Myofiber Growth

Cited by 150 publications

References 69 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

Follistatin-like 1, a Secreted Muscle Protein, Promotes Endothelial Cell Function and Revascularization in Ischemic Tissue through a Nitric-oxide Synthase-dependent Mechanism

Angiotensin II as candidate of cardiac cachexia

Contact Info

Product

Resources

About