Acetaminophen Improves Protein Translational Signaling in Aged Skeletal Muscle

Wu, Mingquan; Liu, Hua; Fannin, Jacqueline; Katta, Anjaiah; Wang, Yeling; Arvapalli, Ravi Kumar; Paturi, Satyanarayana; Karkala, Sunil K.; Rice, Kevin M.; Blough, Eric R.

doi:10.1089/rej.2009.1015

Cited by 25 publications

(24 citation statements)

References 39 publications

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“…Why this shift from an antiapoptotic state (i.e., increased Akt phosphorylation) to one that is more permissive to apoptosis (i.e., diminished Akt phosphorylation) occurs is not well understood but may be related to long-term elevations in the amount of iron-associated reactive oxygen species (ROS). Supporting this contention, our recent data have demonstrated that persistent elevations in oxidative stress, such as that seen during the aging process, are associated with the post-translational modification (S-nitrosylation) of Akt and impairments in Akt enzymatic function and its downstream effectors (Wu et al, 2009b(Wu et al, , 2010a(Wu et al, ,b, 2011). In the current study, we observe reduced Akt activation with iron overload and demonstrate that this finding is reversed by iron chelation.…”

Section: Iron-induced Cardiac Apoptosis and Deferasirox Intervention 61mentioning

confidence: 90%

Iron-Induced Cardiac Damage: Role of Apoptosis and Deferasirox Intervention

Wang

Wu²,

Al-Rousan³

et al. 2010

J Pharmacol Exp Ther

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Excess cardiac iron levels are associated with cardiac damage and can result in increased morbidity and mortality. Here, we hypothesize that elevations in tissue iron can activate caspasedependent signaling, which leads to increased cardiac apoptosis and fibrosis, and that these alterations can be attenuated by iron chelation. Using an iron-overloaded gerbil model, we show that increased cardiac iron is associated with reduced activation of Akt (Ser473 and Thr308), diminished phosphorylation of the proapoptotic regulator Bad (Ser136), and an increased Bax/Bcl-2 ratio. These iron-overload-induced alterations in Akt/ Bad phosphorylation and Bax/Bcl-2 ratio were coupled with increased activation of the downstream caspase-9 (40/38-and 17-kDa fragments) and apoptosis executioner caspase-3 (19-and 17-kDa fragments), which were accompanied by evidence of elevated cytoskeletal ␣-fodrin cleavage (150-and 120-kDa fragments), discontinuity of myocardial membrane dystrophin immunoreactivity, increases in the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells (nucleic DNA fragmentation), and cardiac fibrosis. We demonstrate that the administration of deferasirox, a tridentate iron chelator, is associated with diminished tissue iron deposition, attenuated activation of caspases, reduced ␣-fodrin cleavage, improved membrane integrity, decreased TUNEL reactivity, and attenuated cardiac fibrosis. These results suggest that the activation of caspase-dependent signaling may play a role in the development of iron-induced cardiac apoptosis and fibrosis, and deferasirox, via a reduction in cardiac tissue iron levels, may be useful for decreasing the extent of iron-induced cardiac damage.

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Section: Iron-induced Cardiac Apoptosis and Deferasirox Intervention 61mentioning

confidence: 90%

Iron-Induced Cardiac Damage: Role of Apoptosis and Deferasirox Intervention

Wang

Wu²,

Al-Rousan³

et al. 2010

J Pharmacol Exp Ther

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“…Total protein extracts were prepared and immunoblotting was performed as previously described [13,17,18]. Primary antibodies included anti-GRP78 (#ab21685), anti-CHOP (#sc-575), anti-phospho-eIF2α (#3597S; Cell Signaling Technology (CST), Danvers, MA), anti-eIF2α (#9722; CST), anti-ATF4 (#ab1371; Abcam), anti-caspase 12 (#ab62484; Abcam), anti-c-Jun N-terminal kinase (JNK, #9252; CST), anti-phospho-JNK (#9251S; CST), and anti-glyceraldehyde-3-phosphate dehydrogenase (GAPDH, #2118; CST).…”

Section: Methodsmentioning

confidence: 99%

Acetaminophen Attenuates Obesity-Related Renal Injury Through ER-Mediated Stress Mechanisms

Wang

Arvapalli

et al. 2014

Cell Physiol Biochem

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Background/Aims: Obesity is an independent risk factor for the development of kidney disease. The purpose of this study was to determine how obesity may contribute to renal damage and whether acetaminophen ingestion can diminish obesity-associated renal cell injury in the obese Zucker rat model. Methods: Male obese Zucker rats (4 weeks old, n=6) were treated with acetaminophen (30 mg / kg body weight / day) for 26 weeks. Age matched obese control (OC), obese vehicle (OV, 0.073 mL DMSO/kg/d), and lean Zucker rats (LC) were used to determine the effects of treatment and obesity. Results: Compared to lean control rats, renal lipid deposition, expression of the endoplasmic reticulum (ER) stress protein GRP78 and activation of the ER stress-related eIF2α-ATF4-CHOP, caspase 12, and JNK-MAPK signaling pathways were increased in the obese control and obese vehicle rats. These alterations were associated with the elevated renal cell apoptosis and urinary albumin excretion. Acetaminophen treatment decreased renal lipid deposition, ER-stress related signaling, apoptosis and albuminuria. Conclusion: These data suggest that the protective effects of low dose acetaminophen on renal injury are mediated, at least in part, through attenuation of ER stress.

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“…Previous studies have demonstrated that all of them are validated for use (Aguilera et al, 2011;Averous et al, 2012;Della Pietra et al, 2015;Dixon et al, 2011;Gong et al, 2015;Kim et al, 2011;Li et al, 2012;Murphy et al, 2011;Nissar et al, 2012;Rao et al, 2014;Sarkar and Zohn, 2012;Takeda et al, 2014;Tan et al, 2011;Taniguchi et al, 2011;Wu et al, 2010;Zhang et al, 2011).…”

Section: Antibodiesmentioning

confidence: 99%

HMGB2 regulates satellite-cell-mediated skeletal muscle regeneration through IGF2BP2

Zhou

Huang

et al. 2016

Journal of Cell Science

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Although the mechanism underlying modulation of transcription factors in myogenesis has been well elucidated, the function of the transcription cofactors involved in this process remains poorly understood. Here, we identified HMGB2 as an essential nuclear transcriptional co-regulator in myogenesis. HMGB2 was highly expressed in undifferentiated myoblasts and regenerating muscle. Knockdown of HMGB2 inhibited myoblast proliferation and stimulated its differentiation. HMGB2 depletion downregulated Myf5 and cyclin A2 at the protein but not mRNA level. In contrast, overexpression of HMGB2 promoted Myf5 and cyclin A2 protein upregulation. Furthermore, we found that the RNA-binding protein IGF2BP2 is a downstream target of HMGB2, as previously shown for HMGA2. IGF2BP2 binds to mRNAs of Myf5 or cyclin A2, resulting in translation enhancement or mRNA stabilization, respectively. Notably, overexpression of IGF2BP2 could partially rescue protein levels of Myf5 and cyclin A2, in response to HMGB2 decrease. Moreover, depletion of HMGB2 in vivo severely attenuated muscle repair; this was due to a decrease in satellite cells. Taken together, these results highlight the previously undiscovered and crucial role of the HMGB2-IGF2BP2 axis in myogenesis and muscle regeneration.

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Acetaminophen Improves Protein Translational Signaling in Aged Skeletal Muscle

Abstract: Aging is associated with impairments in the regulation of proteins thought to be important in controlling mRNA translation, and acetaminophen may be useful for the treatment of age-related muscle atrophy by reducing oxidative stress.

Cited by 25 publications

References 39 publications

Iron-Induced Cardiac Damage: Role of Apoptosis and Deferasirox Intervention

Iron-Induced Cardiac Damage: Role of Apoptosis and Deferasirox Intervention

Acetaminophen Attenuates Obesity-Related Renal Injury Through ER-Mediated Stress Mechanisms

HMGB2 regulates satellite-cell-mediated skeletal muscle regeneration through IGF2BP2

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