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Full-Text Articles in Medicine and Health Sciences

Impaired Overload-Induced Hypertrophy Is Associated With Diminished Mtor Signaling In Insulin-Resistant Skeletal Muscle Of The Obese Zucker Rat, Anjaiah Katta, Sudarsanam Kundla, Sunil Kakarla, Miaozong Wu, Jacqueline Fannin, Satyanarayana Paturi, Hua Liu, Hari Addagarla, Eric Blough Feb 2013

Impaired Overload-Induced Hypertrophy Is Associated With Diminished Mtor Signaling In Insulin-Resistant Skeletal Muscle Of The Obese Zucker Rat, Anjaiah Katta, Sudarsanam Kundla, Sunil Kakarla, Miaozong Wu, Jacqueline Fannin, Satyanarayana Paturi, Hua Liu, Hari Addagarla, Eric Blough

Eric Blough

Recent data have suggested that insulin resistance may be associated with a diminished ability of skeletal muscle to undergo hypertrophy (Paturi S, Gutta AK, Kakarla SK, Katta A, Arnold EC, Wu M, Rice KM, Blough ER. J Appl Physiol 108: 7–13, 2010). Here we examine the effects of insulin resistance using the obese Zucker (OZ) rat with increased muscle loading on the regulation of the mammalian target of rapamycin (mTOR) and its downstream signaling intermediates 70-kDa ribosomal protein S6 kinase (p70S6k), ribosomal protein S6 (rpS6), eukaryotic elongation factor 2 (eEF2), and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). Compared with …


Deferasirox Removes Cardiac Iron And Attenuates Oxidative Stress In The Iron-Overloaded Gerbil, Rabaa Al-Rousan, Satyanarayana Paturi, Joseph Laurino, Sunil Kakarla, Anil Gutta, Ernest Walker, Eric Blough Jan 2013

Deferasirox Removes Cardiac Iron And Attenuates Oxidative Stress In The Iron-Overloaded Gerbil, Rabaa Al-Rousan, Satyanarayana Paturi, Joseph Laurino, Sunil Kakarla, Anil Gutta, Ernest Walker, Eric Blough

Eric Blough

Iron-induced cardiovascular disease is the leading cause of death in iron-overloaded patients. Deferasirox is a novel, once daily oral iron chelator that was recently approved for the treatment of transfusional iron overload. Here, we investigate whether deferasirox is capable of removing cardiac iron and improving iron-induced pathogenesis of the heart using the iron overload gerbil model. Animals were randomly divided into three groups: control, iron overload, and iron overload + deferasirox treatment. Iron-dextran was given 100 mg/kg per 5 days i.p for 10 weeks. Deferasirox treatment was taken post iron loading and was given at 100 mg/kg/day p.o for 1 …


Iron-Induced Cardiac Damage: Role Of Apoptosis And Deferasirox Intervention, Yeling Wang, Miaozong Wu, Rabaa Al-Rousan, Hua Liu, Jacqueline Fannin, Satyanarayana Paturi, Ravi Arvapalli, Anjaiah Katta, Sunil Kakarla, Kevin Rice, William Triest, Eric Blough Jan 2013

Iron-Induced Cardiac Damage: Role Of Apoptosis And Deferasirox Intervention, Yeling Wang, Miaozong Wu, Rabaa Al-Rousan, Hua Liu, Jacqueline Fannin, Satyanarayana Paturi, Ravi Arvapalli, Anjaiah Katta, Sunil Kakarla, Kevin Rice, William Triest, Eric Blough

Eric Blough

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 caspase-dependent 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- …