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Type: Artigo de periódico
Title: Ciliary neurotrophic factor infused intracerebroventricularly shows reduced catabolic effects when linked to the TAT protein transduction domain
Author: Vieira, AS
Rezende, ACS
Grigoletto, J
Rogerio, F
Velloso, LA
Skaper, SD
Negro, A
Langone, F
Abstract: Ciliary neurotrophic factor (CNTF) regulates the differentiation and survival of a wide spectrum of developing and adult neurons, including motor neuron loss after injury. We recently described a cell-penetrant recombinant human CNTF (rhCNTF) molecule, formed by fusion with the human immunodeficiency virus-1 transactivator of transcription (TAT) protein transduction domain (TAT-CNTF) that, upon subcutaneous administration, retains full neurotrophic activity without cytokine-like side-effects. Although the CNTF receptor is present in hypothalamic nuclei, which are involved in the control of energy, rhCNTF but not TAT-CNTF stimulates signal transducers and activators of transcription 3 phosphorylation in the rat hypothalamus after subcutaneous administration. This could be due limited TAT-CNTF distribution in the hypothalamus and/or altered intracellular signaling by the fusion protein. To explore these possibilities, we examined the effect of intracerebroventricular administration of TAT-CNTF in male adult rats. TAT-CNTF-induced weight loss, although the effect was smaller than that seen with either rhCNTF or leptin (which exerts CNTF-like effects via its receptor). In contrast to rhCNTF and leptin, TAT-CNTF neither induced morphological changes in adipose tissues nor increased uncoupling protein 1 expression in brown adipose tissue, a characteristic feature of rhCNTF and leptin. Acute intracerebroventricular administration of TAT-CNTF induced a less robust phosphorylation of signal transducers and activators of transcription 3 in the hypothalamus, compared with rhCNTF. The data show that fusion of a protein transduction domain may change rhCNTF CNS distribution, while further strengthening the utility of cell-penetrating peptide technology to neurotrophic factor biology beyond the neuroscience field.
Subject: adipose tissue
ciliary neurotrophic factor
fusion protein
protein transduction domain
signal transducers and activators of transcription 3
Country: EUA
Editor: Wiley-blackwell Publishing, Inc
Citation: Journal Of Neurochemistry. Wiley-blackwell Publishing, Inc, v. 110, n. 5, n. 1557, n. 1566, 2009.
Rights: fechado
Identifier DOI: 10.1111/j.1471-4159.2009.06259.x
Date Issue: 2009
Appears in Collections:Unicamp - Artigos e Outros Documentos

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