Electrical stimulation of neonatal cardiomyocytes results in the sequential activation of nuclear genes governing mitochondrial proliferation and differentiation

Xia, Yang; Buja, L. Maximilian; Scarpulla, Richard C.; McMillin, Jeanie B.

doi:10.1073/pnas.94.21.11399

Cited by 147 publications

(123 citation statements)

References 38 publications

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“…NRF1 expression, similarly to that of NFB, is stimulated by exogenous factors and by endogenous physiological events (Bergeron et al, 2001;Piantadosi and Suliman, 2006;Scarpulla, 2008;Xia et al, 1997). NRF-1 is coordinately involved in the regulation of mitochondrial mass , and is strongly upregulated by LPS in wild-type but not in Tlr4 -/-mice.…”

Section: Introductionmentioning

confidence: 99%

Co-regulation of nuclear respiratory factor-1 by NFκB and CREB links LPS-induced inflammation to mitochondrial biogenesis

Suliman

Sweeney

Withers

et al. 2010

Journal of Cell Science

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The nuclear respiratory factor-1 (NRF1) gene is activated by lipopolysaccharide (LPS), which might reflect TLR4-mediated mitigation of cellular inflammatory damage via initiation of mitochondrial biogenesis. To test this hypothesis, we examined NRF1 promoter regulation by NFκB, and identified interspecies-conserved κB-responsive promoter and intronic elements in the NRF1 locus. In mice, activation of Nrf1 and its downstream target, Tfam, by Escherichia coli was contingent on NFκB, and in LPS-treated hepatocytes, NFκB served as an NRF1 enhancer element in conjunction with NFκB promoter binding. Unexpectedly, optimal NRF1 promoter activity after LPS also required binding by the energy-state-dependent transcription factor CREB. EMSA and ChIP assays confirmed p65 and CREB binding to the NRF1 promoter and p65 binding to intron 1. Functionality for both transcription factors was validated by gene-knockdown studies. LPS regulation of NRF1 led to mtDNA-encoded gene expression and expansion of mtDNA copy number. In cells expressing plasmid constructs containing the NRF-1 promoter and GFP, LPS-dependent reporter activity was abolished by cis-acting κB-element mutations, and nuclear accumulation of NFκB and CREB demonstrated dependence on mitochondrial H2O2. These findings indicate that TLR4-dependent NFκB and CREB activation co-regulate the NRF1 promoter with NFκB intronic enhancement and redox-regulated nuclear translocation, leading to downstream target-gene expression, and identify NRF-1 as an early-phase component of the host antibacterial defenses.

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Section: Introductionmentioning

confidence: 99%

Co-regulation of nuclear respiratory factor-1 by NFκB and CREB links LPS-induced inflammation to mitochondrial biogenesis

Suliman

Sweeney

Withers

et al. 2010

Journal of Cell Science

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“…The putative cAMP response element-binding protein binding site within 1.9Adss1/ CAT was disrupted using a PCR site-directed mutagenesis kit from Stratagene (13). The consensus CRE, TGACGTCA, was mutated to TGtgGTCA as published previously (35). Rat neonatal cardiac myocytes were cultured as above, transfected with plasmid vectors, and assayed for CAT activity and ␤-galactosidase as described (13,36).…”

Section: Rat Neonatal Cardiac Myocyte Culture and Glutamine Treatment-mentioning

confidence: 99%

“…Total cellular RNA (10 g/lane) was electrophoresed in 1.0% agarose under denaturing conditions as described previously (35), and transferred to nylon membranes. RNA was cross-linked to the membrane by ultraviolet irradiation and incubated with an Adss1 probes as described before (13).…”

Section: Rat Neonatal Cardiac Myocyte Culture and Glutamine Treatment-mentioning

confidence: 99%

Mammalian Target of Rapamycin and Protein Kinase A Signaling Mediate the Cardiac Transcriptional Response to Glutamine

Xia¹,

Wen²,

Young³

et al. 2003

Journal of Biological Chemistry

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The addition of glutamine as a major nutrient to cultured neonatal rat cardiomyocytes produced an increase in myocyte size and the organization of actin into myofibrillar arrays. The cellular response was associated with increased abundance of the mRNAs encoding the contractile proteins, ␣-myosin heavy chain and cardiac ␣-actin, and the metabolic enzymes, muscle carnitine palmitoyl transferase I and muscle adenylosuccinate synthetase (ADSS1). Adss1 gene expression was induced ϳ5-fold in glutamine-treated rat neonatal cardiac myocytes. The induction was mediated through the protein kinase A and mammalian target of rapamycin signaling pathways and required a cyclic AMP response element associated with the promoter region of the Adss1 gene. These results highlight glutamine as a major nutrient regulator of cardiac gene expression and identify protein kinase A and mammalian target of rapamycin signaling pathways as mediators of the cardiomyocyte transcriptional response.

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“…The mTFA in turn upregulates the expression of nuclear and mitochondrial genes encoding mitochondrial proteins (Gulick et al, 1994;Wu et al, 1999;Bergeron et al, 2001;Lehman and Kelly, 2002;Vega et al, 2000). The outcome is transcription and replication of key mitochondrial enzymes (Clayton, 1992;Winder et al, 2000), mitochondrial biogenesis to increase mitochondrial oxidative capacity (Williams et al, 1986;Zong et al, 2002) and ATP generation (Xia et al, 1997;Bergeron et al, 2001). Expression of PGC-1α in C2C13 myoblasts cells (Wu et al, 1999), the heart (Lehman et al, 2000;Michael et al, 2001;Lehman and Kelly, 2002;Suzuki et al, 2007) and in skeletal muscle of transgenic mice stimulates mitochondrial biogenesis leading to a dramatic increase of mitochondrial mass and size in neonatal mice and mitogenesis in adult mice (Michael et al, 2001;Lin et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Constitutive activation of AMP-activated protein kinase (AMPK) propel mitochondrial biogenesis

Bokko¹,

Ahmed²,

Fisher³

2014

J. Cell Biol. Genet.

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Mitochondrial biogenesis is primarily a critical adaptation aimed to balance an increased workload in an attempt to maintain appropriate body perfusion. Until recently, the signaling mechanisms responsible for this response are poorly understood. To examine the role of AMP-activated protein kinase (AMPK), an evolutionarily conserved fuel sensor, in mitochondrial biogenesis, we used constitutively active and antisense inhibition genetic tools in Dictyostelium discoideum. Constitutive activation of AMPK culminated in mitochondrial proliferation and elevated ATP generation; this became marked with higher plasmid copies. Antisense inhibition of AMPK yielded non-significant decrease in the mitochondrial content at low levels. However, the more severe the antisense inhibition, the more significant the diminution of AMPK function, resulting in the more apparent decrease in the Advanced Technology Program (ATP) and mitotracker fluorescence. This finding provides direct genetic evidence that AMPK plays a significant role in ameliorating the effects of cellular energy deficit through mitochondrial proliferation. Thus, the constitutive activation of AMPK initiates signalling to downstream targets. The result perturbation of these pathways would culminate in the mitochondrial biogenesis. Taken together, these findings show the constitutive activation of AMPK propels in vivo mitochondrial biogenesis and ATP generation in D. discoideum as in other organisms.

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Electrical stimulation of neonatal cardiomyocytes results in the sequential activation of nuclear genes governing mitochondrial proliferation and differentiation

Abstract: ABSTRACT

Cited by 147 publications

References 38 publications

Co-regulation of nuclear respiratory factor-1 by NFκB and CREB links LPS-induced inflammation to mitochondrial biogenesis

Co-regulation of nuclear respiratory factor-1 by NFκB and CREB links LPS-induced inflammation to mitochondrial biogenesis

Mammalian Target of Rapamycin and Protein Kinase A Signaling Mediate the Cardiac Transcriptional Response to Glutamine

Constitutive activation of AMP-activated protein kinase (AMPK) propel mitochondrial biogenesis

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