Neurogenesis in the mammalian central nervous system is believed to end in the period just after birth; in the mouse striatum no new neurons are produced after the first few days after birth. In this study, cells isolated from the striatum of the adult mouse brain were induced to proliferate in vitro by epidermal growth factor. The proliferating cells initially expressed nestin, an intermediate filament found in neuroepithelial stem cells, and subsequently developed the morphology and antigenic properties of neurons and astrocytes. Newly generated cells with neuronal morphology were immunoreactive for gamma-aminobutyric acid and substance P, two neurotransmitters of the adult striatum in vivo. Thus, cells of the adult mouse striatum have the capacity to divide and differentiate into neurons and astrocytes.

https://science.sciencemag.org/content/sci/255/5052/1707.full.pdf

Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system

Werner, Sabine, and Richard Grose. Regulation of Wound Healing by Growth Factors and Cytokines. Physiol Rev 83: 835–870, 2003; 10.1152/physrev.00032.2002.—Cutaneous wound healing is a complex proce...

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Regulation of Wound Healing by Growth Factors and Cytokines

Atherosclerosis: The Road Ahead

The inflammatory nature of atherosclerosis is well established but the agent(s) that incite inflammation in the artery wall remain largely unknown. Germ-free animals are susceptible to atherosclerosis, suggesting that endogenous substances initiate the inflammation. Mature atherosclerotic lesions contain macroscopic deposits of cholesterol crystals in the necrotic core, but their appearance late in atherogenesis had been thought to disqualify them as primary inflammatory stimuli. However, using a new microscopic technique, we revealed that minute cholesterol crystals are present in early diet-induced atherosclerotic lesions and that their appearance in mice coincides with the first appearance of inflammatory cells. Other crystalline substances can induce inflammation by stimulating the caspase-1-activating NLRP3 (NALP3 or cryopyrin) inflammasome, which results in cleavage and secretion of interleukin (IL)-1 family cytokines. Here we show that cholesterol crystals activate the NLRP3 inflammasome in phagocytes in vitro in a process that involves phagolysosomal damage. Similarly, when injected intraperitoneally, cholesterol crystals induce acute inflammation, which is impaired in mice deficient in components of the NLRP3 inflammasome, cathepsin B, cathepsin L or IL-1 molecules. Moreover, when mice deficient in low-density lipoprotein receptor (LDLR) were bone-marrow transplanted with NLRP3-deficient, ASC (also known as PYCARD)-deficient or IL-1alpha/beta-deficient bone marrow and fed on a high-cholesterol diet, they had markedly decreased early atherosclerosis and inflammasome-dependent IL-18 levels. Minimally modified LDL can lead to cholesterol crystallization concomitant with NLRP3 inflammasome priming and activation in macrophages. Although there is the possibility that oxidized LDL activates the NLRP3 inflammasome in vivo, our results demonstrate that crystalline cholesterol acts as an endogenous danger signal and its deposition in arteries or elsewhere is an early cause rather than a late consequence of inflammation. These findings provide new insights into the pathogenesis of atherosclerosis and indicate new potential molecular targets for the therapy of this disease.

/pdf/nlrp3-inflammasomes-are-required-for-atherogenesis-and-absaoseqwz.pdf

NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals

Epidermal growth factor-related peptides and their receptors in human malignancies

Epidermal growth factor-receptor-protein kinase interactions. Co-purification of receptor and epidermal growth factor-enhanced phosphorylation activity.

Rapid enhancement of protein phosphorylation in A-431 cell membrane preparations by epidermal growth factor.

EPIDERMAL GROWTH FACTOR (EGF) forms a complex with plasma membrane receptors in intact cells that initiates a series of biochemical events resulting in increased cell growth in vivo and in vitro1. The interaction of EGF with membrane receptors has been demonstrated in crude membrane preparations2, but no biochemical alteration of the membrane resulting from hormone binding has been detected. To clarify the molecular mechanisms regulating cell proliferation, specific biochemical reactions initiated by mitogens such as EGF need to be investigated in cell-free systems. As the human epidermoid carcinoma cell line A-431 has an extraordinarily high concentration of EGF receptors3,4 (2–3 x 106 receptors per cell), we have used a crude membrane preparation from these cells to look for an EGF-dependent alteration of membrane structure and/or function. We report here that (1) membranes may be prepared from A-431 cells that retain the ability to bind 125I-labelled EGF in a specific manner, and (2) the binding of EGF to these membranes in vitro results in a marked stimulation of the phosphorylation of endogenous proteins in the presence of [γ-32P]ATP.

Epidermal growth factor stimulates phosphorylation in membrane preparations in vitro.

For cell growth and division to occur, a large variety of metabolic processes must be carefully coordinated in the cell. Through evolutionary pressures, specific hormones and growth factors have acquired the ability to trigger a complex coordinated "pleiotropic growth response" in their target cells. This complex response is mediated by specific cellular receptors and intracellular messengers. Teleologically then, it makes sense that in oncogenesis this growth regulating network is utilized by the production of proteins which mimic growth factors, the activated form of their receptors or, the messengers themselves. Several lines of evidence indicate that the epidermal growth factor-stimulated growth regulatory system is involved in cellular proliferation, both normal and neoplastic. Some of the effects of epidermal growth factor in carcinogenesis are separable from its direct, growth stimulatory effects. Thus, the role of epidermal growth factor in carcinogenesis is more complex than is its role in stimulating growth.

https://cancerres.aacrjournals.org/content/canres/46/3/1030.full.pdf

Lloyd E. King

Papers

Epidermal growth factor-receptor-protein kinase interactions. Co-purification of receptor and epidermal growth factor-enhanced phosphorylation activity.

Rapid enhancement of protein phosphorylation in A-431 cell membrane preparations by epidermal growth factor.

Epidermal growth factor stimulates phosphorylation in membrane preparations in vitro.

Role of epidermal growth factor in carcinogenesis.

Comparison of Epidermal Growth Factor Binding and Receptor Distribution in Normal Human Epidermis and Epidermal Appendages