Musculoskeletal, Neural, and Ocular Physiology Commons^™

Possible Molecular Mechanisms Underlying Age-Related Cardiomyocyte Apoptosis In The F344xbn Rat Heart, Sunil Kakarla, Kevin Rice, Anjaiah Katta, Satyanarayana Paturi, Miaozong Wu, Madhukar Kolli, Saba Keshavarzian, Kamran Manzoor, Paulette Wehner, Eric Blough

Kevin M Rice

Despite advances in treatment, age-related cardiac dysfunction still remains a leading cause of cardiovascular death. Recent data have suggested that increases in cardiomyocyte apoptosis may be involved in the pathological remodeling of heart. Here, we examine the effects of aging on cardiomyocyte apoptosis in 6-, 30-, and 36-month-old Fischer344xBrown Norway F1 hybrid rats (F344XBN). Compared with 6-month hearts, aged hearts exhibited increased TdT-mediated dUTP nick end labeling–positive nuclei, caspase-3 activation, caspase-dependent cleavage of α-fodrin and diminished phosphorylation of protein kinase B/Akt (Thr 308). These age-dependent increases in cardiomyocyte apoptosis were associated with alterations in the composition of the cardiac dystrophin …

Acetaminophen Improves Protein Translational Signaling In Aged Skeletal Muscle, Miaozong Wu, Hua Liu, Jacqueline Fannin, Anjaiah Katta, Yeling Wang, Ravi Kumar Arvapalli, Satyanarayana Paturi, Sunil K. Karkala, Kevin M. Rice, Eric R. Blough

Kevin M Rice

Background: Age-related muscle atrophy is characterized by increased oxidative stress, diminished Akt enzymatic function, and reduced phosphorylation of the mammalian target of rapamycin (mTOR), which can be attenuated by chronic acetaminophen ingestion. Here we hypothesize that age-related impairments in Akt/ mTOR function are associated with reduced protein translational signaling, and that these changes, if present, can be attenuated by acetaminophen treatment. Results: Compared to 6- and 27-month old animals, the expression of the mTOR-complex proteins raptor and GbL and the phosphorylation of tuberin/TSC2 (Thr1462) were reduced in the soleus muscles of very aged rats (33 months old). These changes in …

Altered Regulation Of Contraction-Induced Akt/Mtor/P70s6k Pathway Signaling In Skeletal Muscle Of The Obese Zucker Rat, Anjaiah Katta, Sunil K. Kakarla, Miaozong Wu, Satyanarayana Paturi, Murali K. Gadde, Ravi K. Arvapalli, Madhukar Babu Kolli, Kevin M. Rice, Eric R. Blough

Kevin M Rice

Increased muscle loading results in the phosphorylation of the 70 kDa ribosomal S6 kinase (p70S6k), and this event is strongly correlated with the degree of muscle adaptation following resistance exercise. Whether insulin resistance or the comorbidities associated with this disorder may affect the ability of skeletal muscle to activate p70S6k signaling following an exercise stimulus remains unclear. Here, we compare the contraction-induced activation of p70S6k signaling in the plantaris muscles of lean and insulin resistant obese Zucker rats following a single bout of increased contractile loading. Compared to lean animals, the basal phosphorylation of p70S6k (Thr389; 37.2% and Thr421/Ser424; 101.4%), …

Lean And Obese Zucker Rats Exhibit Different Patterns Of P70s6 Kinase Regulation In The Tibialis Anterior Muscle In Response To High-Force Muscle Contraction, Anjaiah Katta, Sunil K. Karkala, Miaozong Wu, Sarath Meduru, Devashish H. Desai, Kevin M. Rice, Eric R. Blough

Kevin M Rice

Increased phosphorylation of the 70-kDa ribosomal S6 kinase (p70S6k) signaling is strongly correlated with the degree of muscle adaptation following exercise. Herein we compare the phosphorylation of p70S6k, Akt, and mammalian target of rapamycin (mTOR) in the tibialis anterior (TA) muscles of lean and obese Zucker rats following a bout of eccentric exercise. Exercise increased p70S6k (Thr389) phosphorylation immediately after (33.3 ± 7.2%) and during [1 h (24.0 ± 14.9%) and 3 h (24.6 ± 11.3%)] recovery in the lean TA and at 3 h (33.5 ± 8.0%) in the obese TA Zucker rats. mTOR (Ser2448) phosphorylation was elevated in …

Aging-Associated Dysfunction Of Akt/Protein Kinase B: S-Nitrosylation And Acetaminophen Intervention, Miaozong Wu, Anjaiah Katta, Murali K. Gadde, Hua Liu, Sunil K. Kakarla, Jacqueline Fannin, Satyanarayana Paturi, Ravi K. Arvapalli, Kevin M. Rice, Yeling Wang, Eric R. Blough

Kevin M Rice

Background: Aged skeletal muscle is characterized by an increased incidence of metabolic and functional disorders, which if allowed to proceed unchecked can lead to increased morbidity and mortality. The mechanism(s) underlying the development of these disorders in aging skeletal muscle are not well understood. Protein kinase B (Akt/PKB) is an important regulator of cellular metabolism and survival, but it is unclear if aged muscle exhibits alterations in Akt function. Here we report a novel dysfunction of Akt in aging muscle, which may relate to S-nitrosylation and can be prevented by acetaminophen intervention.

Principal Findings: Compared to 6- and 27-month rats, …

Age-Related Dystrophin–Glycoprotein Complex Structure And Function In The Rat Extensor Digitorum Longus And Soleus Muscle, Kevin M. Rice, Deborah L. Preston, David Neff, Michael L. Norton, Eric R. Blough

Kevin M Rice