| Full text | |
| Author(s): |
Vieira, Andre S.
[1]
;
Rezende, Alexandre C. S.
[1]
;
Grigoletto, Jessica
[2]
;
Rogerio, Fabio
[1]
;
Velloso, Licio A.
[3]
;
Skaper, Stephen D.
[4]
;
Negro, Alessandro
[2]
;
Langone, Francesco
[1]
Total Authors: 8
|
| Affiliation: | [1] Univ Estadual Campinas, Dept Genet Evolut & Bioagents, Campinas, SP - Brazil
[2] Univ Padua, CRIBI, Dept Vet Sci, Padua - Italy
[3] Univ Estadual Campinas, Dept Internal Med, Campinas, SP - Brazil
[4] Univ Padua, CRIBI, Dept Pharmacol & Anesthesiol, Padua - Italy
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | Journal of Neurochemistry; v. 110, n. 5, p. 1557-1566, SEP 2009. |
| Web of Science Citations: | 16 |
| 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. (AU) | |