Protein kinase B

HIV-1 and ARV drugs uptake during pregnancy may change placental phenotype during pregnancy affecting fetal growth. We investigated the influence of maternal HIV-1 and ARV drugs on expression of placental genes important for fetus growth. A total 51 HIV-1 positives and 46 HIV-1 negative pregnant women were studied. Placental gene expression changes of insulin-like growth factor receptor 1 (IGF-1) R, mammalian target of rapamycin (mTOR), protein kinase B (AKT-1), sodium-coupled neutral amino acid transporters (Slc38a1, Slca38a2, Slc38a4), inhibin A, adrenomedullin and 11 beta-Hydroxysteroid dehydrogenase type (HSD)-2 were assessed by RT-qPCR. There was a significant decrease in mRNA expression of placental IGF-1R, mTOR, and AKT-1 in HIV-1 positive placentas compared to controls (p < 0.0001). There was also significant upregulation of an antiangiogenic molecule, inhibin A and downregulation of angiogenic molecule adrenomedullin in HIV-1 positive placenta (all p < 0.0001). However, the mRNA expression of placental Slc38a1 and Slca38a2 was higher in both HIV-1 positive and negative women delivering LBW babies compared to controls (p < 0.0001). The placental mRNA expression of 11 β-HSD-2 increased by 17 folds in HIV-1 negative and by 3.8 folds in HIV-1 positive women delivering LBW babies. IGF-1-P13-AKT-1-mTOR signaling pathway is dysregulated in placenta of HIV-1 positive women on ARV drugs. Higher mRNA expression levels of inhibin A and lower levels of adrenomedullin occur in placenta of HIV-1 positive women delivering LBW babies. ARV drugs and HIV-1 may be involved in the disruption of vascular tone of the placenta and therefore placental perfusion.

The tumor suppressor gene PTEN is frequently mutated in diverse human cancers and in autosomal dominant cancer predisposition disorders. Recent studies have shown that the lipid phosphatase activity of PTEN is critical for its tumor suppressor function and that PTEN negatively regulates the phosphatidylinositol 3&#39;-kinase-protein kinase B pathway. Although more than half of PTEN mutations result in protein truncation, a significant fraction of PTEN mutations are missense mutations. To examine whether tumor-derived and germ-line-derived missense mutations inactivate PTEN lipid phosphatase function, we constructed 42 distinct types of PTEN missense mutations and expressed them in Escherichia coli. The purified (His)6-tagged PTEN proteins were tested for their ability to dephosphorylate inositol 1,3,4,5-tetrakisphosphate and phosphatidylinositol 3,4,5-triphosphate. In addition, we examined the effect of mutant PTENs on the ability of PTEN to bind to the phospholipid membrane. The re...

Pro-inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) play a key role in the pathogenesis of osteoarthritis (OA). Anti-inflammatory agents capable of suppressing the production and catabolic actions of these cytokines may have therapeutic potential in the treatment of OA and a range of other osteoarticular disorders. The purpose of this study was to examine the effects

Biomass burning is a major source of indoor air pollution in rural India. The authors investigated in this study whether cumulative exposures to biomass smoke cause activation of the serine/threonine kinase Akt in airway cells and peripheral blood lymphocytes (PBL). For this, the authors enrolled 87 premenopausal (median age 34 years), nonsmoking women who used to cook with biomass (wood, dung, crop wastes) and 85 age-matched control women who cooked with cleaner fuel liquefied petroleum gas. Immunocytochemical and immunoblotting assays revealed significantly higher levels of phosphorylated forms of Akt protein (p-Aktser473 and p-Aktthr308) in PBL, airway epithelial cells, alveolar macrophages, and neutrophils in sputum of biomass-using women than control. Akt activation in biomass users was associated with marked rise in generation of reactive oxygen species and concomitant depletion of superoxide dismutase. Measurement of particulate matter having a diameter of less than 10 and 2.5 µm in indoor air by real-time aerosol monitor showed 2 to 4 times more particulate pollution in biomass-using households, and Akt activation was positively associated with particulate pollution after controlling potential confounders. The findings suggest that chronic exposure to biomass smoke activates Akt, possibly via generation of oxidative stress.

A novel series of Akt/PKB inhibitors derived from a screening lead (1) has been prepared. The novel trans-3, 4′-bispyridinylethylenes described herein are potent inhibitors of Akt/PKB with IC50 values in the low double-digit nanomolar range against Akt1. ...

Obesity is associated with an increased risk for insulin resistance, a state characterized by impaired responsiveness of liver, muscle and adipose tissue to insulin. One class of lipids involved in the development of insulin resistance are the (glyco)sphingolipids. Ceramide, the most simple sphingolipid, directly inhibits phosphorylation of the insulin signaling mediator Akt/Protein Kinase B. More complex glycosphingolipids, so-called gangliosides, block

Previous studies indicate that a continual source of adenosine 5&#39;-triphosphate is required for both opening and closing of stomata. However, vanadate (Na,VO, at 500 p~) as well as a light/dark transition induced stomatal closing in epidermal peels of Com- melina communis L., showing that the stoppage or even the de- crease of the activity of the plasma membrane H+-adenosine 5&#39;-triphosphatase

Background— Recent evidence from cultured endothelial cell studies suggests that phosphorylation of endothelial nitric oxide synthase (eNOS) through the PI3-kinase– Akt pathway increases NO production. This study was designed to elucidate the signaling pathway involved in the antiapoptotic effect of insulin in vivo and to test the hypothesis that phosphorylation of eNOS by insulin may participate in the cardioprotective effect of insulin after myocardial ischemia and reperfusion. Methods and Results— Male Sprague-Dawley rats were subjected to 30 minutes of myocardial ischemia and 4 hours of reperfusion. Rats were randomized to receive vehicle, insulin, insulin plus wortmannin, or insulin plus L-NAME. Treatment with insulin resulted in 2.6-fold and 4.3-fold increases in Akt and eNOS phosphorylation and a significant increase in NO production in ischemic/reperfused myocardial tissue. Phosphorylation of Akt and eNOS and increase of NO production by insulin were completely blocked by wo...

We analysed the effects of resistance exercise upon the phosphorylation state of proteins associated with adaptive processes from the Akt/PKB (protein kinase B) and the mitogen-activated protein kinase (MAPK) pathways. Nine healthy young men (21.7 ± 0.55 year) performed 10 sets of 10 leg extensions at 80% of their 1-RM (repetition maximum). Muscle biopsies were taken from the vastus lateralis at rest, within the first 30 s after exercise and at 24 h post-exercise. Immediately post exercise, the phosphorylation states of Akt/PKB on Thr308 and Ser473 and 4E-BP1 on Thr37/46 (eukaryotic initiation factor 4E-binding protein 1) were decreased (−60 to −90%, P s6k (p70 ribosomal S6 kinase) on Thr421/Ser424 was increased more than 20-fold (P P s6k on Thr421/Ser424 and sarcoplasmic ERK1/2 were elevated. The present results indicate that high-intensity resistance exercise in the fasted state inhibits Akt/PKB and 4E-BP1 whilst concomitantly augmenting MAPK signalling and p70s6k on Thr421/Ser424.