HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1α

Arany, Zoltàn; Foo, ShiYin; Ma, Yue; Ruas, Jorge L.; Bommi-Reddy, Archana; Girnun, Geoffrey D.; Cooper, Marcus P.; Laznik, Dina; Chinsomboon, Jessica; Rangwala, Shamina M.; Baek, Kwan-Hyuck; Rosenzweig, Anthony; Spiegelman, Bruce M.

doi:10.1038/nature06613

Cited by 950 publications

(925 citation statements)

References 22 publications

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“…multiple nuclear transcriptional regulators, including PGC-1a, PGC-1b, NRF1, GABP, PPARa, PPARd, and ERRs (13)(14)(15)(53)(54)(55). Perm1 also led to enhanced levels of PGC1a and ERRa, suggesting that the effects of Perm1 on gene expression are at least in part mediated through increases in these transcriptional regulators.…”

Section: Discussionmentioning

confidence: 95%

“…The coactivators PGC-1a and PGC-1b and the nuclear receptors ERRa and ERRg also drive skeletal muscle angiogenesis, at least in part via the induction of Vegfa (15)(16)(17). Changes in fiber-type composition are thought to be primarily under the control of NFAT, though they are also controlled by PGC-1a, PGC-1b, PPARd, and ERRb/ERRg (17)(18)(19)(20)(21)(22)(23)(24).…”

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confidence: 99%

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Perm1 enhances mitochondrial biogenesis, oxidative capacity, and fatigue resistance in adult skeletal muscle

et al. 2015

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Skeletal muscle mitochondrial content and oxidative capacity are important determinants of muscle function and whole‐body health. Mitochondrial content and function are enhanced by endurance exercise and impaired in states or diseases where muscle function is compromised, such as myopathies, muscular dystrophies, neuromuscular diseases, and age‐related muscle atrophy. Hence, elucidating the mechanisms that control muscle mitochondrial content and oxidative function can provide new insights into states and diseases that affect muscle health. In past studies, we identified Perm1 (PPARGC1‐ and ESRR‐induced regulator, muscle 1) as a gene induced by endurance exercise in skeletal muscle, and regulating mitochondrial oxidative function in cultured myotubes. The capacity of Perm1 to regulate muscle mitochondrial content and function in vivo is not yet known. In this study, we use adeno‐associated viral (AAV) vectors to increase Perm1 expression in skeletal muscles of 4‐wk‐old mice. Compared to control vector, AAV1‐Perm1 leads to significant increases in mitochondrial content and oxidative capacity (by 40‐80%). Moreover, AAV1‐Perm1‐transduced muscles show increased capillary density and resistance to fatigue (by 33 and 31 %, respectively), without prominent changes in fiber‐type composition. These findings suggest that Perm1 selectively regulates mitochondrial biogenesis and oxidative function, and implicate Perm1 in muscle adaptations that also occur in response to endurance exercise.—Cho, Y., Hazen, B. C., Gandra, P. G., Ward, S. R., Schenk, S., Russell, A. P., Kralli, A. Perm1 enhances mitochondrial biogenesis, oxidative capacity, and fatigue resistance in adult skeletal muscle. FASEB J. 30, 674‐687 (2016). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 95%

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confidence: 99%

Perm1 enhances mitochondrial biogenesis, oxidative capacity, and fatigue resistance in adult skeletal muscle

et al. 2015

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“…Evidence for a role for PGC-1α in skeletal muscle angiogenesis was first demonstrated by Arany et al (2008) where C2C12 myotubes transfected with virus expressing PGC-1α resulted in a 14-fold increase in VEGF mRNA expression. In addition, upregulation of VEGF mRNA following O2 depravation treatment (Arany et al, 2008) or β-adrenergic stimulation (Chinsomboon et al, 2009) has shown to be significantly lower in muscle cells derived from PGC-1α knock-out mice, compared with wild-type controls.…”

Section: Vegf and Angiogenesismentioning

confidence: 99%

“…In addition, upregulation of VEGF mRNA following O2 depravation treatment (Arany et al, 2008) or β-adrenergic stimulation (Chinsomboon et al, 2009) has shown to be significantly lower in muscle cells derived from PGC-1α knock-out mice, compared with wild-type controls. The necessity of PGC-1α in VEGF mediated angiogenesis has also been demonstrated using exercise models, where capillary density was shown to be significantly increased in wild-type controls compared with PGC-1α muscle knock-out mice following 14 days of voluntary running (Chinsomboon et al, 2009).…”

Section: Vegf and Angiogenesismentioning

confidence: 99%

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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“…For mitochondrial biogenesis, PGC-1α activates nuclear-encoded and mitochondria-encoded genes involved in mitochondrial DNA proliferation and protein expression in a coordinated manner 38) . It also regulates VEGF expression and angiogenesis through the pathway not involving the canonical hypoxia response pathway and hypoxia inducible factor (HIF) 39) . PGC-1α also improves glucose transport activity of the skeletal muscle by increasing GLUT 4 expression 40) .…”

Section: Intracellular Signaling Involved In Endurance Traininginducementioning

confidence: 99%

Reactive oxygen species and endurance training-induced adaptations

Matsui

2013

JPFSM

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Endurance training induces mitochondrial biogenesis and angiogenesis in skeletal muscle. Endurance training also improves insulin sensitivity at both the skeletal muscle and whole body level. Recently, ROS have been suggested to play an important role in endurance training-induced adaptations. However, this hypothesis is not yet fully supported. To advance understanding of the role of ROS and antioxidants in endurance training-induced adaptations, efforts should be made in future studies to clarify the sites of ROS production and the influence of antioxidants on the redox status under each training condition. Effort should also be directed to identifying the signaling pathways involved. In this situation, it should be recognized that in vivo cellular signaling is redundant. Therefore, efforts to evaluate the relative importance and interactions among the multiple cellular signaling pathways involved in each training condition are required. Without elucidating the role of ROS and antioxidants in endurance traininginduced adaptations, then evidence-based sound advice regarding antioxidant supplementation cannot be made.

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HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1α

Cited by 950 publications

References 22 publications

Perm1 enhances mitochondrial biogenesis, oxidative capacity, and fatigue resistance in adult skeletal muscle

Perm1 enhances mitochondrial biogenesis, oxidative capacity, and fatigue resistance in adult skeletal muscle

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

Reactive oxygen species and endurance training-induced adaptations

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