Neuroprotective function of thymosin-β and its derivative peptides on the programmed cell death of chick and rat neurons

doi:10.1016/j.bbrc.2007.08.031

Biochemical and Biophysical Research Communications

Volume 362, Issue 3, 26 October 2007, Pages 587-593

https://doi.org/10.1016/j.bbrc.2007.08.031 Get rights and content

Abstract

Thymosin-βs (Tβs) are small polypeptides with various biological functions, including cytoskeletal remodeling, angiogenesis, cellular migration, wound healing, and regulation of apoptosis. Recently, we found that Tβ is involved in the control of programmed cell death (PCD) of motoneurons (MNs) in chick embryo, and that the anti-apoptotic action of Tβ is independent of its actin-sequestering activity. In this study, we observed that a synthetic peptide derived from Tβ suppressed staurosporine-induced neuronal apoptosis in vitro, and PCD of chick or rat MNs in vivo. Furthermore, inhibition of Tβ4 in chick embryo by antibody significantly augmented the PCD of MNs, suggesting that secreted form of Tβ is physiological regulator of PCD. Based on these findings, we propose that extracellularly secreted Tβ is involved in the control of PCD of neurons during development, and Tβ-derived peptides could be useful for the anti-apoptotic therapy of neuropathologies related to neuronal apoptosis.

Section snippets

Materials and methods

Fertilized eggs. Fertilized chicken eggs were incubated at 38 °C in a humidified incubator. On E3, eggs were then windowed and incubated until the appropriate stages. Stage of chick embryo was identified based on the Hamburger and Hamiliton criteria [17]. For peptide treatments, solutions containing peptides were directly applied onto the allantoids membranes through the egg windows, sealed, and returned to the incubator.

Peptides. Tβ-derived peptides were commercially synthesized (Peptron, South

Anti-apoptotic activity of Tβ-derived peptides in vitro

The peptide derived from Tβ4 (P-T4, LKKTETQ) has been reported to have healing activity of cornea [20]. We first asked whether this or related peptides exerts anti-apoptotic action in cultured neurons. Following 24 h after staurosporine (100 nM) treatment, there was about 70% loss of neurons by apoptosis (Fig. 1). However, treatment of the cultured neurons with staurosporine together with P-T4 suppressed neuronal apoptosis dose dependently. Similar anti-apoptotic activity was seen with the

Discussion

In this study, we provided an evidence that extracellular Tβs may exert anti-apoptotic effects on developing MNs. Previously, we observed that the anti-apoptotic action of Tβs was independent of their intracellular actin remodeling activity, because mutant Tβs lacking actin-sequestering activity still maintained an anti-apoptotic function. Furthermore, the viability of untransfected MNs surrounding the Tβ-transfected MNs was also significantly increased [28], suggesting that Tβs secreted from

Acknowledgments

Supported by the Korea Science Engineering Foundation grant funded by the Korea government (M10412000078-04N1200-07810 and M103KV010018-03K2201-01820K).

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The ability of embryonic Tβ4 to bolster migration of cardiomyocytes and endothelial progenitor cells can also be observed after cardiac damage in the adult heart (described in Section 3) and is currently being pursued as a therapeutic strategy in cardiac tissue engineering (Section 4). Interestingly, Tβ4 has also been explicitly linked to fetal development of many other organ systems (Choi, Noh, Kim, Sun, & Kim, 2007; Dathe & Brand-Saberi, 2004; Nemolato et al., 2009; Wang et al., 2012) and adult tumorigenesis. Tβ4 along with Tβ10 and other β-thymosins are released from developing salivary glands of the neonate and act in a paracrine manner to induce differentiation of the oral cavity.
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Citation Excerpt :
Cell culture. Primary cerebral cortex neuronal cultures were prepared from the cerebral cortex of gestation day 17 embryos (E17) SD rats, as previously described [8]. For immunocytochemistry and time-lapse analyses, cells were plated onto the glass coverslips coated with poly-d-lysine.
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Neuroprotective function of thymosin-β and its derivative peptides on the programmed cell death of chick and rat neurons

Abstract

Section snippets

Materials and methods

Anti-apoptotic activity of Tβ-derived peptides in vitro

Discussion

Acknowledgments

Int. J. Biochem. Cell Biol.

Brain Res.

Clin. Biochem.

Arch. Biochem. Biophys.

Exp. Eye Res.

Biochim. Biophys. Acta

Biochem. Biophys. Res. Commun.

Curr. Biol.

Mol. Cell Neurosci.

Biochem. Pharmacol.

Biochem. Biophys. Res. Commun.

Brain Res.

FEBS Lett.

Exp. Cell Res.

Trends Neurosci.

Brain Res

Neuron

Neuroscience

Nuclear localisation of the G-actin sequestering peptide thymosin β4

J. Cell Sci.

Thymosins: both nuclear and cytoplasmic proteins

Eur. J. Biochem.

β thymosins as actin binding peptides

Bioessays

β-thymosin is required for axonal tract formation in developing zebrafish brain

Development