Management of cellular energy by the AMP‐activated protein kinase system

Hardie, D. Grahame; Scott, John W.; Pan, Di; Hudson, Emma R.

doi:10.1016/s0014-5793(03)00560-x

Cited by 747 publications

(583 citation statements)

References 78 publications

(76 reference statements)

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“…Elevated levels of cellular AMP are known to activate signaling cascades initiated in part by allosteric binding to AMP-activated protein kinase (AMPK) [20]. We therefore measured the ability of membrane-permeable AMP (8-Br-AMP) to induce loss of H3 phosphorylation at various doses and found that, unlike 8-Br-cAMP, it failed to do so ( Fig.…”

Section: Effects Of Other Nucleotides On H3 Phosphorylationmentioning

confidence: 99%

cAMP signaling induces rapid loss of histone H3 phosphorylation in mammary adenocarcinoma-derived cell lines

Rodriguez-Collazo

Snyder

Chiffer

et al. 2008

Experimental Cell Research

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The phosphorylation of histone H3 is known to play a role in regulation of transcription as well as preparation of chromosomes for mitosis. Various signaling cascades induce H3 phosphorylation, particularly at genes activated by these pathways. In this study we show that signaling can also have the opposite effect. Activators of cAMP signaling induce a rapid and potent loss of H3 phosphorylation. This effect is not mediated through a cAMP metabolite since a membranepermeable form of AMP had no effect on H3 phosphorylation and a phosphodiesterase-resistant cAMP analog efficiently reduced it. cAMP is also the likely regulator of H3 phosphorylation under physiological conditions since only supra-pharmacological doses of cGMP induce the loss of H3 phosphorylation. The loss of phosphorylation is specific for histone H3 since we do not observe drastic losses in total phosphorylation of other histones. In addition, other H3 modifications are unaffected with the exception of lysine 9 methylation, which is elevated. Analysis of cell growth and cell cycle show that cAMP signaling inhibits cell growth and arrests cells at both G1 and G2/M. Similar effects of cAMP signaling on H3 phosphorylation are observed in a variety of mammary adenocarcinoma-derived cell lines. In syngeneic human breast derived cell lines, one diploid and non-transformed, the other derived from a ductal carcinoma, the loss of H3 phosphorylation is significantly more sensitive to cAMP concentration in the transformed cell line.

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Section: Effects Of Other Nucleotides On H3 Phosphorylationmentioning

confidence: 99%

cAMP signaling induces rapid loss of histone H3 phosphorylation in mammary adenocarcinoma-derived cell lines

Rodriguez-Collazo

Snyder

Chiffer

et al. 2008

Experimental Cell Research

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“…Energy depletion by hypoglycemia, hypoxia, and ischemia activates AMPK [17,35] to restore ATP levels [26]. Interestingly, brain injury increases AMPK catalytic subunit expression in reactive astrocytes [53].…”

Section: Introductionmentioning

confidence: 99%

A pharmacological activator of AMP-activated protein kinase (AMPK) induces astrocyte stellation

Favero

Mandell

2007

Brain Research

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AMP-activated protein kinase (AMPK) represents a key energy-sensing molecule in many cell types. Because astrocytes are key mediators of metabolic signaling in the brain, we have initiated studies on the expression and activation of AMPK in these cells. Treatment of cultured rat cortical astrocytes with a pharmacological AMPK activator, AICA-riboside (AICAR) resulted in a time-and concentration-dependent increase in phosphorylation of AMPK and acetyl-CoA carboxylase (ACC), a direct substrate. AICAR treatment also induced a transition from epithelioid to stellate morphology in a time-and concentration-dependent manner. As stellation is indicative of actin cytoskeletal reorganization, the formation of stress fibers and focal adhesions in response to AICAR was assessed. AICAR-induced stellation correlated with F-actin disassembly and focal adhesion dispersal. Furthermore, transient transfection of an activated RhoA construct prevented AICAR-induced stellation, indicating a mechanism upstream of RhoA. Use of pharmacological inhibitor compound C prevented AICAR-induced stellation demonstrating necessity of AMPK activity for the response. Our findings suggest that AMPK mediates morphological alterations of astrocytes in response to energy depletion.

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“…AMP-activated protein kinase (AMPK) is the downstream component of a protein kinase cascade that plays a key role in regulating energy metabolism [1][2][3]. AMPK is activated by an increase in the AMP:ATP ratio within the cell, and in response phosphorylates a number of targets leading to a decrease in energy utilising pathways and an increase in energy producing pathways.…”

Section: Introductionmentioning

confidence: 99%

Exercise in rats does not alter hypothalamic AMP-activated protein kinase activity

Andersson

Treebak²,

Nielsen³

et al. 2005

Biochemical and Biophysical Research Communications

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Abbreviations: Acetyl-CoA carboxylase, ACC; AMP-activated protein kinase, AMPK; peptide YY 3-36, PYY 3-36 ;Key words: AMP-activated protein kinase, energy metabolism, exercise, hypothalamus Hypothalamic AMPK and exercise; Andersson et al. AbstractRecent studies have demonstrated that AMP-activated protein kinase (AMPK) in the hypothalamus is involved in the regulation of food intake. Because exercise is known to influence appetite and causes substrate depletion it may also influence AMPK in the hypothalamus. Male rats either rested or ran for 30 or 60 min on a treadmill (22m/min, 10% slope) and were sacrificed immediately after exercise or after 60 min recovery either in the fasted state or after oral gavage with glucose (3g/kg body weightbw). Exercise decreased muscle and liver glycogen substantially.Hypothalamic total or α2-associated AMPK activity and phosphorylation state of the AMPK substrate acetyl-CoA carboxylase (ACC) were not changed significantly immediately following treadmill running or during fed or fasted recovery. Plasma grehlin increased (p<0.05) by 40% during exercise whereas the concentration of PYY was unchanged. In recovery, glucose feeding increased plasma glucose and insulin concentrations whereas grehlin and PYY decreased to (grehlin) or below (PPY) resting levels. It is concluded that 1 h of strenuous exercise in rats does not elicit significant changes in hypothalamic AMPK activity despite an increase in plasma ghrelin. Thus, changes in energy metabolism during or after exercise are likely not coordinated by changes in hypothalamic AMPK activity. Hypothalamic AMPK and exercise; Andersson et al.3

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Management of cellular energy by the AMP‐activated protein kinase system

Cited by 747 publications

References 78 publications

cAMP signaling induces rapid loss of histone H3 phosphorylation in mammary adenocarcinoma-derived cell lines

cAMP signaling induces rapid loss of histone H3 phosphorylation in mammary adenocarcinoma-derived cell lines

A pharmacological activator of AMP-activated protein kinase (AMPK) induces astrocyte stellation

Exercise in rats does not alter hypothalamic AMP-activated protein kinase activity

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