Thymosin β as an Actin-binding Protein with a Variety of Functions

Kuzan, Aleksandra

doi:10.17219/acem/32026

Cited by 27 publications

(17 citation statements)

References 23 publications

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“…Parathymosin (PTMS) and thymosin beta 4 (TMSB4X) interacting nodes belong to the thymosin family and are involved in binding and polymerization of actin and therefore in cell motility, proliferation, and inflammation processes [30,31]. Thymosin beta 4 and thymosin beta 10 peptides as well as their related C-terminal truncated forms identified in ependymoma tissue by top-down approach were already characterized by our group in other tissues of PF pediatric brain tumors, marking the medulloblastoma aggressive histotype [19].…”

Section: Discussionmentioning

confidence: 99%

Ependymoma Pediatric Brain Tumor Protein Fingerprinting by Integrated Mass Spectrometry Platforms: A Pilot Investigation

Rossetti

Massimi

Martelli

et al. 2020

Cancers

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Ependymoma pediatric brain tumor occurs at approximate frequencies of 10-15% in supratentorial and 20-30% in posterior fossa regions. These tumors have an almost selective response to surgery and relative and confirmed resistance to radiotherapy and chemotherapic agents, respectively. Alongside histopathological grading, clinical and treatment evaluation of ependymomas currently consider the tumor localization and the genomic outlined associated molecular subgroups, with the supratentorial and the posterior fossa ependymomas nowadays considered diverse diseases. On these grounds and in trying to better understand the molecular features of these tumors, the present investigation aimed to originally investigate the proteomic profile of pediatric ependymoma tissues of different grade and localization by mass spectrometry platforms to disclose potential distinct protein phenotypes. To this purpose, acid-soluble and acid-insoluble fractions of ependymoma tumor tissues homogenates were analyzed by LC-MS following both the top-down and the shotgun proteomic approaches, respectively, to either investigate the intact proteome or its digested form. The two approaches were complementary in profiling the ependymoma tumor tissues and showed distinguished profiles for supratentorial and posterior fossa ependymomas and for WHO II and III tumor grades. Top-down proteomic analysis revealed statistically significant higher levels of thymosin beta 4, 10 kDa heat shock protein, non-histone chromosomal protein HMG-17, and mono-/uncitrullinated forms ratio of the glial fibrillary acidic protein (GFAP) fragment 388-432 in supratentorial ependymomas-the same GFAP fragment as well as the hemoglobin alpha-and the beta-chain marked grade II with respect to grade III posterior fossa ependymomas. Gene ontology classification of shotgun data of the identified cancer and the non-cancer related proteins disclosed protein elements exclusively marking tumor localization and pathways that were selectively overrepresented. These results, although preliminary, seem consistent with different protein profiles of ependymomas of diverse grade of aggressiveness and brain region development and contributed to enlarging the molecular knowledge of this still enigmatic tumor.

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Section: Discussionmentioning

confidence: 99%

Ependymoma Pediatric Brain Tumor Protein Fingerprinting by Integrated Mass Spectrometry Platforms: A Pilot Investigation

Rossetti

Massimi

Martelli

et al. 2020

Cancers

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“…Tβ4 is a small molecule composed of 43 amino acid residues. It is involved in multiple responses, such as wound healing, tissue development, angiogenesis, and myocardial repair (24–27). Tβ4 can inhibit apoptosis and exerts neuroprotective effects (28).…”

Section: Discussionmentioning

confidence: 99%

Effects of thymosin β4 on neuronal apoptosis in a rat model of cerebral ischemia‑reperfusion injury

2019

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The aim of the present study was to investigate the protective effects of thymosin β4 (Tβ4) on neuronal apoptosis in rat middle cerebral artery occlusion ischemia/reperfusion (MCAO I/R) injury, and determine the mechanisms involved in this process. Forty-eight adult male Sprague-Dawley rats were randomly divided into three groups (n=16 per group): A sham control group, an ischemia/reperfusion group (I/R group), and a Tβ4 group. The focal cerebral I/R model was established by blocking the right MCA for 2 h, followed by reperfusion for 24 h. The Zea-Longa method was used to assess neurological deficits. Cerebral infarct volume was assessed using 2,3,5-triphenyltetrazolium chloride staining, and pathological changes were observed via hematoxylin and eosin staining. The terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay was used to detect apoptosis. The expression of glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), and caspase-12 (CASP12) protein was assessed using immunohistochemistry and western blotting 24 h after reperfusion. Infarct volume and neuronal damage in the I/R and Tβ4 groups were significantly greater than those observed in the sham group. The Zea-Longa score, neuronal apoptosis, and expression of GRP78, CHOP, and CASP12 in the I/R and Tβ4 groups were significantly higher than those reported in the sham group. However, the Longa score and neuronal apoptosis were lower in the Tβ4 group compared to the I/R group. The expression of GRP78 was significantly increased, whereas that of CHOP and CASP12 was significantly decreased in the Tβ4 group compared to the I/R group. The present data revealed that Tβ4 can inhibit neuronal apoptosis by upregulating GRP78 and downregulating CHOP and CASP12, thereby reducing cerebral I/R injury.

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“…The full-length Tβ4 polypeptide has been shown to be effective in reducing inflammation and to be associated with wound healing, hair growth, immunomodulation, and angiogenesis. 10 It is also reported that Tβ4 is induced by several nonsteroidal anti-inflammatory drugs, 11 supporting its role in anti-inflammation. Moreover, Tβ4 polypeptide down-regulated H 2 O 2 -triggered activation of the extracellular Signal-regulated Kinase and Jun N-terminal kinase/mitogen-activated protein kinase, as well as nuclear factor kappa light chain enhancer of activated B cells, suggesting that these signaling pathways might be involved in the anti-inflammatory effects of Tβ4 activation.…”

Section: Secreted Moonlighting Proteins In Anti-inflammatory Signaturmentioning

confidence: 91%

Moonlighting Activity of Secreted Inflammation-Regulatory Proteins

2018

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Moonlighting proteins exhibit multiple activities in different cellular compartments, and their abnormal regulation could play an important role in many diseases. To date, many proteins have been identified with moonlighting activity, and more such proteins are being gradually identified. Among the proteins that possess moonlighting activity, several secreted proteins exhibit multiple activities in different cellular locations, such as the extracellular matrix, nucleus, and cytoplasm. While acute inflammation starts rapidly and generally disappears in a few days, chronic inflammation can last for months or years. This is generally because of the failure to eliminate the cause of inflammation, along with repeated exposure to the inflammatory agent. Chronic inflammation is now considered as an overwhelming burden to the general wellbeing of patients and noted as an underlying cause of several diseases. Moonlighting proteins can contribute to the process of chronic inflammation; therefore, it is imperative to overview some proteins that exhibit multiple functions in inflammatory diseases. In this review, we will focus on inflammation, particularly unravelling several well-known secreted proteins with multiple functions in different cellular locations.

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Thymosin β as an Actin-binding Protein with a Variety of Functions

Cited by 27 publications

References 23 publications

Ependymoma Pediatric Brain Tumor Protein Fingerprinting by Integrated Mass Spectrometry Platforms: A Pilot Investigation

Ependymoma Pediatric Brain Tumor Protein Fingerprinting by Integrated Mass Spectrometry Platforms: A Pilot Investigation

Effects of thymosin β4 on neuronal apoptosis in a rat model of cerebral ischemia‑reperfusion injury

Moonlighting Activity of Secreted Inflammation-Regulatory Proteins

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