IKKα and alternative NF-κB regulate PGC-1β to promote oxidative muscle metabolism

Bakkar, Nadine; Ladner, Katherine J.; Canan, Benjamin D.; Liyanarachchi, Sandya; Bal, Naresh C.; Pant, Meghna; Periasamy, Muthu; Li, Qiutang; Janssen, Paul M. L.; Guttridge, Denis C.

doi:10.1083/jcb.201108118

Cited by 65 publications

(62 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This indicates a switch toward noncanonical/alternative NF-B signaling. A recent publication outlined that alternative signaling via IKK␣ and RelB induces an oxidative phenotype in muscle driven by PGC-1␤ (51). Furthermore, activation of c-Rel and p50 was suggested to play a role in disuse atrophy (52).…”

Section: Discussionmentioning

confidence: 99%

The Peroxisome Proliferator-activated Receptor γ Coactivator 1α/β (PGC-1) Coactivators Repress the Transcriptional Activity of NF-κB in Skeletal Muscle Cells

Eisele

Salatino

Sobek

et al. 2013

Journal of Biological Chemistry

162

View full text Add to dashboard Cite

Background: Peroxisome proliferator-activated receptor ␥ coactivator 1 (PGC) ␣ and PGC-1␤ are metabolic coactivators that are dysregulated in muscle in many chronic diseases. Results: PGC-1␣ and PGC-1␤ differentially suppress expression of proinflammatory cytokines induced by various stimuli. Conclusion: In muscle cells, PGC-1␣ and PGC-1␤ modulate the NF-B pathway thus profoundly affecting inflammatory processes. Significance: Targeting PGC-1␣ and PGC-1␤ in chronic diseases might reduce inflammation and thereby reverse disease progression.

show abstract

Section: Discussionmentioning

confidence: 99%

The Peroxisome Proliferator-activated Receptor γ Coactivator 1α/β (PGC-1) Coactivators Repress the Transcriptional Activity of NF-κB in Skeletal Muscle Cells

Eisele

Salatino

Sobek

et al. 2013

Journal of Biological Chemistry

162

View full text Add to dashboard Cite

show abstract

“…It is unclear whether NF-B is a promyogenic or an anti-myogenic factor during muscle differentiation as relevant data are conflicting, but suppression of myogenesis by means of inhibiting MyoD, myogenin and myofibrillar gene expression has been linked to canonical NF-B signaling [244][245][246][247][248][249][250][251][252]. In contrast, noncanonical NF-B signaling that involves IKK and RelB does not affect myogenesis but drives an oxidative muscle fiber switch by targeting PGC-1 which stimulates mitochondrial biogenesis [253]. Exercise-dependent NF-B activation has also been reported in skeletal muscle and potentially induces ROS defense, regeneration of damaged fibers and adaptations in fuel metabolism [254][255][256].…”

Section: Inflammatory Pathways In Skeletal Musclementioning

confidence: 99%

Functional crosstalk of PGC-1 coactivators and inflammation in skeletal muscle pathophysiology

Eisele

Handschin

2013

Semin Immunopathol

View full text Add to dashboard Cite

(150 -250 words) [165] Skeletal muscle is an organ involved in whole body movement and energy metabolism with the ability to dynamically adapt to different states of (dis-)use. At a molecular level, the peroxisome proliferatoractivated receptor  coactivators 1 (PGC-1) are important mediators of oxidative metabolism in skeletal muscle and in other organs. Musculoskeletal disorders as well as obesity and its sequelae are associated with PGC-1 dysregulation in muscle with a concomitant local or systemic inflammatory reaction. In this review, we outline the function of PGC-1 coactivators in physiological and pathological conditions as well as the complex interplay of metabolic dysregulation and inflammation in obesity with special focus on skeletal muscle. We further put forward the hypothesis that in this tissue, oxidative metabolism and inflammatory processes mutually antagonize each other. The nuclear factor κB (NF-B) pathway thereby plays a key role in linking metabolic and inflammatory programs in muscle cells. We conclude this review with a perspective about the consequences of such a negative crosstalk on the immune system and the possibilities this opens for clinical applications.

show abstract

“…Our laboratory recently implicated the alternative NF-κB signaling pathway in the regulation of PGC-1β transcription (Bakkar et al, 2012). In contrast to canonical NF-κB signaling, the alternative pathway is regulated by an IκB kinase α (IKKα) homodimer complex, which phosphorylates the p100 precursor protein, resulting in its partial proteolysis and formation of the mature p52 subunit of NF-κB (Oeckinghaus et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

MyoD Regulates Skeletal Muscle Oxidative Metabolism Cooperatively with Alternative NF-κB

et al. 2016

View full text Add to dashboard Cite

SUMMARY MyoD is a key regulator of skeletal myogenesis that directs contractile protein synthesis, but whether this transcription factor also regulates skeletal muscle metabolism has not been explored. In a genome-wide ChIP-seq analysis of skeletal muscle cells, we unexpectedly observed that MyoD directly binds to numerous metabolic genes, including those associated with mitochondrial biogenesis, fatty acid oxidation, and the electron transport chain. Results in cultured cells and adult skeletal muscle confirmed that MyoD regulates oxidative metabolism through multiple transcriptional targets including PGC-1β, a master regulator of mitochondrial biogenesis. We find that PGC-1β expression is cooperatively regulated by MyoD and the alternative NF-κB signaling pathway. Bioinformatics evidence suggests that this cooperativity between MyoD and NF-κB extends to other metabolic genes as well. Together, these data identify MyoD as a regulator of the metabolic capacity of mature skeletal muscle to ensure that sufficient energy is available to support muscle contraction.

show abstract

IKKα and alternative NF-κB regulate PGC-1β to promote oxidative muscle metabolism

Abstract: Alternative NF-κB signaling modulates the activity of PGC-1β to promote oxidative metabolism in skeletal muscle.

Cited by 65 publications

References 70 publications

The Peroxisome Proliferator-activated Receptor γ Coactivator 1α/β (PGC-1) Coactivators Repress the Transcriptional Activity of NF-κB in Skeletal Muscle Cells

The Peroxisome Proliferator-activated Receptor γ Coactivator 1α/β (PGC-1) Coactivators Repress the Transcriptional Activity of NF-κB in Skeletal Muscle Cells

Functional crosstalk of PGC-1 coactivators and inflammation in skeletal muscle pathophysiology

MyoD Regulates Skeletal Muscle Oxidative Metabolism Cooperatively with Alternative NF-κB

Contact Info

Product

Resources

About