Publication Title: 

Akt is a highly regulated serine/threonine kinase involved in stress response and cell survival. Stress response pathways must cope with increasing chronic stress susceptibility with age. We found an age-related lesion in Akt activity via loss of phosphorylation on Ser473. In hepatocytes from old rats, basal phospho-Ser473 Akt is 30% lower when compared to young, but basal phospho-Thr308 Akt is unchanged.

Shay, Kate Petersen
Hagen, Tory M.
Publication Title: 
The Journal of Neuroscience: The Official Journal of the Society for Neuroscience

Altered folate homeostasis is associated with many clinical and pathological manifestations in the CNS. Notably, folate-mediated one-carbon metabolism is essential for methyltransferase-dependent cellular methylation reactions. Biogenesis of protein phosphatase 2A (PP2A) holoenzyme containing the regulatory B(alpha) subunit, a major brain tau phosphatase, is controlled by methylation.

Sontag, Jean-Marie
Nunbhakdi-Craig, Viyada
Montgomery, Lisa
Arning, Erland
Bottiglieri, Teodoro
Sontag, Estelle
Publication Title: 
The Journal of Neuroscience: The Official Journal of the Society for Neuroscience

Both insulin resistance (type II diabetes) and beta-amyloid (Abeta) oligomers are implicated in Alzheimer's disease (AD). Here, we investigate the role of Abeta oligomer-induced c-Jun N-terminal kinase (JNK) activation leading to phosphorylation and degradation of the adaptor protein insulin receptor substrate-1 (IRS-1). IRS-1 couples insulin and other trophic factor receptors to downstream kinases and neuroprotective signaling. Increased phospho-IRS-1 is found in AD brain and insulin-resistant tissues from diabetics.

Ma, Qiu-Lan
Yang, Fusheng
Rosario, Emily R.
Ubeda, Oliver J.
Beech, Walter
Gant, Dana J.
Chen, Ping Ping
Hudspeth, Beverly
Chen, Cory
Zhao, Yongle
Vinters, Harry V.
Frautschy, Sally A.
Cole, Greg M.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Disorders of water balance are among the most common and morbid of the electrolyte disturbances, and are reflected clinically as abnormalities in the serum sodium concentration. The transient receptor potential vanilloid 4 (TRPV4) channel is postulated to comprise an element of the central tonicity-sensing mechanism in the mammalian hypothalamus, and is activated by hypotonic stress in vitro. A nonsynonymous polymorphism in the TRPV4 gene gives rise to a Pro-to-Ser substitution at residue 19.

Tian, Wei
Fu, Yi
Garcia-Elias, Anna
Fernández-Fernández, José M.
Vicente, Rubén
Kramer, Patricia L.
Klein, Robert F.
Hitzemann, Robert
Orwoll, Eric S.
Wilmot, Beth
McWeeney, Shannon
Valverde, Miguel A.
Cohen, David M.
Publication Title: 
Schizophrenia Research

BACKGROUND: D-serine is an allosteric modulator of the brain N-methyl-d-aspartate (NMDA) receptor and a potential novel treatment of schizophrenia. Double-blind studies have been performed at 30 mg/kg/day (approximately 2 g/day) with encouraging results, but no formal dose escalation studies have been performed. We describe the first evaluation of the efficacy and safety of d-serine at doses >30 mg/kg/day; a 4-week, open-label trial of adjunctive D-serine (30, 60 or 120 mg/kg/day). METHODS: 42 antipsychotic-stabilized patients with schizophrenia or schizoaffective disorder participated.

Kantrowitz, Joshua T.
Malhotra, Anil K.
Cornblatt, Barbara
Silipo, Gail
Balla, Andrea
Suckow, Raymond F.
D'Souza, Cyril
Saksa, John
Woods, Scott W.
Javitt, Daniel C.
Publication Title: 
Protein engineering, design & selection: PEDS

Post-translational modifications (PTMs) play a crucial role during biogenesis of many transmembrane proteins. Previously, it had not been possible to evaluate PTMs in cystic fibrosis transmembrane conductance regulator (CFTR), the epithelial ion channel responsible for cystic fibrosis, because of difficulty obtaining sufficient amounts of purified protein. We recently used an inducible overexpression strategy to generate recombinant CFTR protein at levels suitable for purification and detailed analysis.

McClure, Michelle
DeLucas, Lawrence J.
Wilson, Landon
Ray, Marjorie
Rowe, Steven M.
Wu, Xiaoyun
Dai, Qun
Hong, Jeong S.
Sorscher, Eric J.
Kappes, John C.
Barnes, Stephen
Publication Title: 

We previously reported that genistein, a phytoestrogen, up-regulates endothelial nitric oxide synthase (eNOS) and prevents hypertension in rats that are independent of estrogen signaling machinery. However, how genistein regulates eNOS expression is unknown. In the present study, we show that genistein enhanced eNOS expression and NO synthesis in primary human aortic endothelial cells. Inhibition of extracellular signal regulated kinase, phosphoinositol-3 kinase, or protein kinase C did not affect genistein-enhanced eNOS expression and NO synthesis.

Si, Hongwei
Yu, Jie
Jiang, Hongling
Lum, Hazel
Liu, Dongmin
Publication Title: 
FEBS letters

The influence of caloric restriction (CR) on the activities of hepatic serine metabolizing enzymes in young (3 months) and old (30 months) mice was studied. Serine dehydratase (SDH) activity increased markedly with age in both diet groups and in old mice was higher in the CR group. No effects of CR were observed in the young. Serine:pyruvate transaminase (SPT) and glycerate kinase activities were unaffected by age and diet. However, glycerate dehydrogenase activity was decreased in old CR mice but not in young CR.

Hagopian, Kevork
Ramsey, Jon J.
Weindruch, Richard
Publication Title: 
Biochemical and Biophysical Research Communications

We examined in HepG2 cells whether glucose-induced changes in AMP-activated protein kinase (AMPK) activity could be mediated by SIRT1, an NAD(+)-dependent histone/protein deacetylase that has been linked to the increase in longevity caused by caloric restriction. Incubation with 25 vs. 5mM glucose for 6h concurrently diminished the phosphorylation of AMPK (Thr 172) and ACC (Ser 79), increased lactate release, and decreased the abundance and activity of SIRT1. In contrast, incubation with pyruvate (0.1 and 1mM) for 2h increased AMPK phosphorylation and SIRT1 abundance and activity.

Suchankova, Gabriela
Nelson, Lauren E.
Gerhart-Hines, Zachary
Kelly, Meghan
Gauthier, Marie-Soleil
Saha, Asish K.
Ido, Yasuo
Puigserver, Pere
Ruderman, Neil B.
Publication Title: 

Glycine inhibitory dysfunction provides a useful experimental model for studying the mechanism of dynamic mechanical allodynia, a widespread and intractable symptom of neuropathic pain. In this model, allodynia expression relies on N-methyl-d-aspartate receptors (NMDARs), and it has been shown that astrocytes can regulate their activation through the release of the NMDAR coagonist d-serine. Recent studies also suggest that astrocytes potentially contribute to neuropathic pain. However, the involvement of astrocytes in dynamic mechanical allodynia remains unknown.

Miraucourt, Loïs S.
Peirs, Cédric
Dallel, Radhouane
Voisin, Daniel L.


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