IL-1beta impairs insulin-like growth factor i-induced differentiation and downstream activation signals of the insulin-like growth factor i receptor in myoblasts.

Proinflammatory cytokines are elevated in disorders characterized by muscle wasting and weakness, such as inflammatory myopathies and AIDS wasting. We recently demonstrated that TNF-alpha impairs the ability of insulin-like growth factor (IGF)-I to promote protein synthesis in muscle precursor cells. In this study we extend these findings by showing that low concentrations of IL-1beta impair IGF-I-dependent differentiation of myoblasts, as assessed by expression of the muscle specific protein, myosin heavy chain.

IL-1beta suppresses prolonged Akt activation and expression of E2F-1 and cyclin A in breast cancer cells.

Cell cycle aberrations occurring at the G(1)/S checkpoint often lead to uncontrolled cell proliferation and tumor growth. We recently demonstrated that IL-1beta inhibits insulin-like growth factor (IGF)-I-induced cell proliferation by preventing cells from entering the S phase of the cell cycle, leading to G(0)/G(1) arrest. Notably, IL-1beta suppresses the ability of the IGF-I receptor tyrosine kinase to phosphorylate its major docking protein, insulin receptor substrate-1, in MCF-7 breast carcinoma cells.

Glutamate receptor subtypes in human retinal horizontal cells.

Glutamate receptor currents were examined in horizontal cells from cultured human retina using whole-cell recording procedures. Horizontal cells possess both AMPA and kainate receptors and both produce significant sustained currents. The kainate-induced current did not show significant desensitization and was not enhanced by concanavalin A.

Tumor necrosis factor alpha inhibits insulin-like growth factor I-induced hematopoietic cell survival and proliferation.

Proinflammatory cytokines, such as TNFalpha and IL-1beta, are both cytostatic and cytotoxic. In contrast, IGF-I promotes proliferation and survival of hematopoietic progenitor cells. In this report, we establish that both the cytostatic and cytotoxic activity of TNFalpha on murine myeloid progenitor cells is only evident in the presence of IGF-I.

Tumor necrosis factor alpha inhibits cyclin A expression and retinoblastoma hyperphosphorylation triggered by insulin-like growth factor-I induction of new E2F-1 synthesis.

Cyclin A is required for cell cycle S phase entry, and its overexpression contributes to tumorigenesis. Release of pre-existing E2Fs from inactive complexes of E2F and hypophosphorylated retinoblastoma (RB) is the prevailing dogma for E2F transcriptional activation of target genes such as cyclin A. Here we explored the hypothesis that new synthesis of E2F-1 is required for insulin-like growth factor-I (IGF-I) to induce cyclin A accumulation and RB hyperphosphorylation, events that are targeted by tumor necrosis factor alpha (TNFalpha) to arrest cell cycle progression.

[Combination therapy with losartan and fosinopril for early diabetic nephropathy].

Objective: To observe the effects of combined use of losartan and fosinopril in the treatment of early diabetic nephropathy.

Methods: Fifty-seven patients with diabetic nephropathy were divided equally into group A with treatment with losartan (50 mg) and fosinopril (10 mg) daily, group B with daily losartan treatment (50-100 mg), and group C with fosinopril treatment at the daily dose of 10-20 mg. After the 6-month medication, the patients underwent examinations for changes in the mean arterial blood pressure (MABP), serum creatinine (SCr), blood urea nitrogen (BUN) and 24-h urine protein excretion.

Cytokine-hormone interactions: tumor necrosis factor alpha impairs biologic activity and downstream activation signals of the insulin-like growth factor I receptor in myoblasts.

TNFalpha is elevated following damage to skeletal muscle. Here we provide evidence that TNFalpha acts on muscle cells to induce a state of IGF-I receptor resistance. We establish that TNFalpha inhibits IGF-I-stimulated protein synthesis in primary porcine myoblasts.

A gene trap Dissociation insertion line, associated with a RING-H2 finger gene, shows tissue specific and developmental regulated expression of the gene in Arabidopsis.

Real interesting new gene (RING) finger proteins act as E3 ubiquitin-protein ligases and play critical roles in targeting the destruction of proteins of diverse functions in all eukaryotes, ranging from yeast to mammals. Arabidopsis genome contains a large number of genes encoding RING finger proteins. In this report we describe the identification of more than 40 RING-H2 finger proteins that are of small size, not more than 200 amino acids, and contain no other recognizable protein-protein interaction domain(s).

A non-excitatory paradigm of glutamate toxicity.

Retinal ganglion cells are driven by glutamatergic synapses, but they are also very susceptible to glutamate toxicity. Whereas the conventional excitotoxicity model of glutamate-induced cell death requires membrane depolarization, we have found that glutamate toxicity need not be linked with excitation. A large subset of ganglion cells possesses high-affinity kainate receptors that are calcium permeable.

Manipulation of leaf shape by modulation of cell division.

The role of cell division as a causal element in plant morphogenesis is debatable, with accumulating evidence supporting the action of cell division-independent mechanisms. To directly test the morphogenic function of cell division, we have utilised a microinduction technique to locally and transiently manipulate the expression in transgenic plants of two genes encoding putative effectors of the cell cycle, a tobacco A-type cyclin and a yeast cdc25. The results show that local expression of these genes leads to modulation of cell division patterns.