Nitric oxide and AMPK cooperatively regulate PGC-1α in skeletal muscle cells

Lira, Vitor A.; Brown, Dana L.; Lira, Ana; Kavazis, Andreas N.; Soltow, Quinlyn A.; Zeanah, Elizabeth H.; Criswell, David S.

doi:10.1113/jphysiol.2010.194035

Cited by 168 publications

(144 citation statements)

References 63 publications

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“…This indicates that that NO signalling is both upstream and downstream of AMPK and CaMK, respectively. Similar findings were demonstrated by Lira et al (2010), where pharmacological inhibition of AMPK attenuated PGC-1α mRNA expression, despite co-treatment with NO donors. It was also shown that PGC-1α mRNA expression was attenuated when muscle cells were treated with NOS inhibitor, L-NAME despite co-treatment with AICAR.…”

Section: Nitric Oxidesupporting

confidence: 82%

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PGC-1α Mediated Muscle Aerobic Adaptations to Exercise, Heat and Cold Exposure

Ihsan¹,

Watson²,

Abbiss³

2014

Cell Mol Exerc Physiol

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PGC-1α is regarded as a key regulator of mitochondrial biogenesis due to its central role in regulating the activity of key transcription factors associated with encoding mitochondrial components. Additionally, PGC-1α has shown to mediate adaptations that increase fat metabolism and angiogenesis, contributing to the overall oxidative phenotype of the muscle. While it is well established that exercise is a potent stimulator of PGC-1α, recent evidence indicates that heat and cold exposures may also influence mitochondrial biogenesis through the up-regulation of PGC-1α. This highlights the potential use of these modalities in conjunction with exercise to enhance training adaptations. As such, the purpose of this review is to describe the possible mechanisms and pathways by which exercise, as well as hot and cold exposures may influence mitochondrial biogenesis. It is clear that changes in intracellular calcium, oxidative stress and phosphorylation potential are major up-regulators of PGC-1α during exercise. Moreover, there is evidence implicating calcium signalling, in addition to β-adrenergic activation in cold-induced mitochondrial biogenesis, while PGC-1α during heat exposure is likely triggered by changes in phosphorylation potential and nitric oxide signalling. However, these mechanisms appear to change considerably when cold/heat is administered following exercise, and seem to be dependent on the experimental models used (i.e. in vitro vs. in vivo, rodent vs. human). Understanding the effects heat/cold exposure and its interaction with exercise may lead to the optimisation and development of temperature-related interventions to enhance training adaptations, or aid in the treatment of mitochondrial related diseases.

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Section: Nitric Oxidesupporting

confidence: 82%

“…1) (Lira et al, 2010;McConell et al, 2010). In a recent study, McConell et al (2010) showed that AMPK and CaMK were activated in L6 myocytes treated with NO donors, in line with increased protein expressions of PGC-1α, COX1 and COX4.…”

Section: Nitric Oxidementioning

confidence: 96%

PGC-1α Mediated Muscle Aerobic Adaptations to Exercise, Heat and Cold Exposure

Ihsan¹,

Watson²,

Abbiss³

2014

Cell Mol Exerc Physiol

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“…PGC-1␣ expression is increased in response to nitric oxide in an AMPKdependent fashion (30). Following exposure to exogenous nitric oxide, PGC-1␣ is increased in wild-type (WT) MEFs, while nitric oxide-induced expression of PGC-1␣ is absent in IRE1␣ Ϫ/Ϫ cells (Fig.…”

Section: Nitricmentioning

confidence: 99%

IRE1-Dependent Activation of AMPK in Response to Nitric Oxide

Meares

Hughes

Naatz

et al. 2011

Molecular and Cellular Biology

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While there can be detrimental consequences of nitric oxide production at pathological concentrations, eukaryotic cells have evolved protective mechanisms to defend themselves against this damage. The unfoldedprotein response (UPR), activated by misfolded proteins and oxidative stress, is one adaptive mechanism that is employed to protect cells from stress. Nitric oxide is a potent activator of AMP-activated protein kinase (AMPK), and AMPK participates in the cellular defense against nitric oxide-mediated damage in pancreatic ␤-cells. In this study, the mechanism of AMPK activation by nitric oxide was explored. The known AMPK kinases LKB1, CaMKK, and TAK1 are not required for the activation of AMPK by nitric oxide. Instead, this activation is dependent on the endoplasmic reticulum (ER) stress-activated protein IRE1. Nitric oxide-induced AMPK phosphorylation and subsequent signaling to AMPK substrates, including Raptor, acetyl coenzyme A carboxylase, and PGC-1␣, is attenuated in IRE1␣-deficient cells. The endoribonuclease activity of IRE1 appears to be required for AMPK activation in response to nitric oxide. In addition to nitric oxide, stimulation of IRE1 endoribonuclease activity with the flavonol quercetin leads to IRE1-dependent AMPK activation. These findings indicate that the RNase activity of IRE1 participates in AMPK activation and subsequent signaling through multiple AMPK-dependent pathways in response to nitrosative stress.Nitric oxide, an important mediator of both physiological and pathological processes, has been implicated in the development of a number of inflammatory diseases. When produced at low concentrations, nitric oxide can promote cell growth and survival. At high concentrations, such as those produced during inflammation by inducible nitric oxide synthase (iNOS), nitric oxide induces extensive cellular injury that includes DNA damage, inhibition of oxidative metabolism, and induction of endoplasmic reticulum (ER) stress (5, 12, 39). Pancreatic ␤-cells are exquisitely sensitive to oxidative damage, as glucose-stimulated insulin secretion requires the oxidation of glucose to CO 2 , resulting in the accumulation of ATP. Nitric oxide, produced in micromolar concentrations in response to interleukin 1 (IL-1) and gamma interferon (IFN-␥), mediates the damaging effects of these cytokines on ␤-cell function (3, 33). While nitric oxide stimulates cellular damage, it also activates a number of signaling pathways that limit additional cellular damage and repair existing damage. In pancreatic ␤-cells, the protective responses activated by nitric oxide include (i) JNK-dependent induction of GADD45␣ (growth arrest and DNA damage-inducible protein 45␣) and DNA repair, (ii) activation of AMP-activated protein kinase (AMPK), resulting in enhanced metabolic recovery, and (iii) activation of the unfolded-protein response (UPR) (25,34,38,54,57,61).AMPK is a conserved heterotrimeric (␣, ␤, and ␥ subunits) serine/threonine kinase involved in sensing and responding to the energetic demand within eukaryotic cel...

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“…In turn, PGC-1a is transcriptionally regulated by p-CREB, which promotes PGC-1a expression in the presence of cold and fasting stimulus (27). Besides that, the transcriptional activity of PGC-1a is also modulated by post-translational modifications, e.g., deactivation by SIRT1 and phosphorylation by AMPK (28,29). AMPK is switched on by an increase of AMP-ATP ratio, which results in AMPK phosphorylation.…”

Section: Dysfunction Of Mitochondrial Biogenesis Is Highly Involved Imentioning

confidence: 99%

Depressed mitochondrial biogenesis and dynamic remodeling in mouse tibialis anterior and gastrocnemius induced by 4‐week hindlimb unloading

et al. 2012

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SummaryMitochondrial dynamics is highly involved in muscle atrophy, the slow twitch muscle as soleus, preferentially affected by hindlimb unloading (HU), was well characterized by mitochondrial dysfunction in biogenesis. However, the fast twitch muscles like tibialis anterior (TA) and gastrocnemius (GAS), which are the most massive parts of the hindlimb muscles, are less elucidated on mitochondrial adaptations responding to HU. To investigate the mitochondrial dynamic responses and the involved molecules mediating atrophy in TA and GAS, we studied a 4-week HU mouse model. We found GAS was preferentially affected to atrophy by unloading compared with TA. Furthermore, the depressed mitochondrial biogenesis occurred, accounting for mitochondrial loss in GAS by unloading. PGC-1a, as well as its transcriptional/post-translational modification regulators, such as p-CREB, SIRT1, and p-AMPK, were consistently reduced in response to unloading in GAS. Molecules relevant to autophagy, mitochondrial fusion, and fission, were compromised following unloading both in TA and GAS. These results suggested that TA exhibited resistance to unloading induced muscle atrophy while GAS presented significant mitochondrial loss, which might be due to the mitochondrial biogenesis suppressed by the inactivation of PGC-1a. However, both in TA and GAS muscles, a similar sedentary mitochondrial dynamics of mitochondrial fusion and fission was induced by unloading though TA exhibited little muscle atrophy. IUBMBIUBMB Life, 64(11): 901-910, 2012

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Nitric oxide and AMPK cooperatively regulate PGC-1α in skeletal muscle cells

Cited by 168 publications

References 63 publications

PGC-1α Mediated Muscle Aerobic Adaptations to Exercise, Heat and Cold Exposure

PGC-1α Mediated Muscle Aerobic Adaptations to Exercise, Heat and Cold Exposure

IRE1-Dependent Activation of AMPK in Response to Nitric Oxide

Depressed mitochondrial biogenesis and dynamic remodeling in mouse tibialis anterior and gastrocnemius induced by 4‐week hindlimb unloading

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