Peroxisome Proliferator-activated Receptor γ Co-activator 1-α as a Critical Co-activator of the Murine Hepatic Oxidative Stress Response and Mitochondrial Biogenesis in Staphylococcus aureus Sepsis

Cherry, Anne D.; Suliman, Hagir B.; Bartz, Raquel R.; Piantadosi, Claude A.

doi:10.1074/jbc.m113.512483

Cited by 71 publications

(57 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A direct comparison of transcript levels specifically for catalase, Sod1, Sod2, HO1, Nqo1 and Gsta4 in hearts of treated and control mice showed that expression of these genes was significantly higher in SFN-treated animals (Table 2). In silico or in vitro analysis of the Gsta4, Nqo-1, Ho-1 and Sod2 promoter regions revealed consensus ARE binding sites for the Nfe2l2 (Nrf2) transcription factor [72-75]. On the other hand, most of the examined transcript levels (with the exception of Pxdn, Gpx4, Txnrd1, Gsta1+2, Gsta3, Gstm1, Aor and Gclm ) were expressed at lower levels in the DOX-treated group.…”

Section: Resultsmentioning

confidence: 99%

Sulforaphane protects the heart from doxorubicin-induced toxicity

Singh

Sharma

McElhanon

et al. 2015

Free Radical Biology and Medicine

116

View full text Add to dashboard Cite

Cardiotoxicity is one of the major side effects encountered during cancer chemotherapy with doxorubicin (DOX) and other anthracyclines. Previous studies have shown that oxidative stress caused by DOX is one of the primary mechanisms for its toxic effects on the heart. Since the redox-sensitive transcription factor, Nrf2, plays a major role in protecting cells from the toxic metabolites generated during oxidative stress, we examined the effects of the phytochemical sulforaphane (SFN), a potent Nrf2-activating agent, on DOX-induced cardiotoxicity. These studies were carried out both in vitro and in vivo using rat H9c2 cardiomyoblast cells and wild type 129/sv mice, and involved SFN pretreatment followed by SFN administration during DOX exposure. SFN treatment protected H9c2 cells from DOX cytotoxicity and also resulted in restored cardiac function and a significant reduction in DOX-induced cardiomyopathy and mortality in mice. Specificity of SFN induction of Nrf2 and protection of H9c2 cells was demonstrated in Nrf2 knockdown experiments. Cardiac accumulation of 4-hydroxynonenal (4-HNE) protein adducts, due to lipid peroxidation following DOX-induced oxidative stress, was significantly attenuated by SFN treatment. The respiratory function of cardiac mitochondria isolated from mice exposed to DOX alone was repressed, while SFN treatment with DOX significantly elevated mitochondrial respiratory complex activities. Co-administration of SFN reversed the DOX-associated reduction in nuclear Nrf2 binding activity and restored cardiac expression of Nrf2-regulated genes, at both the RNA and protein levels. Together, our results demonstrate for the first time that the Nrf2 inducer, SFN, has the potential to provide protection against DOX-mediated cardiotoxicity.

show abstract

Section: Resultsmentioning

confidence: 99%

Sulforaphane protects the heart from doxorubicin-induced toxicity

Singh

Sharma

McElhanon

et al. 2015

Free Radical Biology and Medicine

116

View full text Add to dashboard Cite

show abstract

“…PGC-1α was reported to interact with nuclear respiratory factor 1 (NRF1) and nuclear factor erythroid 2 (NF-E2)-related factor 2 (NRF2) to regulate mitochondrial biogenesis, oxidative stress response and energy generation (10,14,18,58). Sirt3 was reported to be regulated by PGC-1α and ERRα in brown adipocytes (17).…”

Section: Pgc-1α Interacts With Transcription Factor Errα To Regulate mentioning

confidence: 99%

PGC-1α/ERRα-Sirt3 Pathway Regulates DAergic Neuronal Death by Directly Deacetylating SOD2 and ATP Synthase β

ZhangXuefei

RenXiaoqing

ZHANGQi

et al. 2016

Antioxidants & Redox Signaling

111

View full text Add to dashboard Cite

show abstract

“…NFE2L2 trans -activates genes of the antioxidant response 191 , and is coactivated by PGC-1α during oxidative stress 192, 193 . The loss of redox capacity seen in aging is similarly observed in hearts lacking NFE2L2 194, 195 .…”

Section: Exercise and Mitochondrial Dysfunction In The Aged Heartmentioning

confidence: 99%

The Role of Exercise in Cardiac Aging

Roh

Rhee

Chaudhari

et al. 2016

Circulation Research

118

View full text Add to dashboard Cite

Aging induces structural and functional changes in the heart that are associated with increased risk of cardiovascular disease and impaired functional capacity in the elderly. Exercise is a diagnostic and therapeutic tool, with the potential to provide insights into clinical diagnosis and prognosis, as well as the molecular mechanisms by which aging influences cardiac physiology and function. In this review, we first provide an overview of how aging impacts the cardiac response to exercise and the implications this has for functional capacity in older adults. We then review the underlying molecular mechanisms by which cardiac aging contributes to exercise intolerance, and conversely how exercise training can potentially modulate aging phenotypes in the heart. Finally, we highlight the potential use of these exercise models to complement models of disease in efforts to uncover new therapeutic targets to prevent or treat heart disease in the aging population.

show abstract

Peroxisome Proliferator-activated Receptor γ Co-activator 1-α as a Critical Co-activator of the Murine Hepatic Oxidative Stress Response and Mitochondrial Biogenesis in Staphylococcus aureus Sepsis

Cited by 71 publications

References 49 publications

Sulforaphane protects the heart from doxorubicin-induced toxicity

Sulforaphane protects the heart from doxorubicin-induced toxicity

PGC-1α/ERRα-Sirt3 Pathway Regulates DAergic Neuronal Death by Directly Deacetylating SOD2 and ATP Synthase β

The Role of Exercise in Cardiac Aging

Contact Info

Product

Resources

About