<p>Thymosin β4 prevents oxygen-glucose deprivation/reperfusion-induced injury in rat cortical neurons</p>

Abstract

Purpose: This study investigated whether thymosin (T) β4 protects against oxygen-glucose deprivation/reperfusion (OGD/R) injury in rat cortical neurons, as well as the underlying mechanisms. Methods: Primary rat cortical neurons were transfected with Tβ4 overexpression plasmid; the transfection efficiency was confirmed by detecting Tβ4 expression by fluorescence quantitative PCR and Western blotting. The OGD/R model was established and apoptotic cells were quantified by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling. Structural changes in the endoplasmic reticulum were visualized by transmission electron microscopy. The expression levels of 78-kDa glucose-regulated protein (GRP) 78, C/EBP-homologous protein (CHOP), B-cell lymphoma (Bcl)-2, and Bcl-2-associated X protein (Bax) were determined by Western blotting. The effect of Tβ4 on OGD/R injury was evaluated by adding exogenous Tβ4 to neuronal cultures. Results: Cortical neurons were identified by the expression of neuron-specific enolase. In OGD/R cells, the rate of apoptosis was increased and GRP78, CHOP, and Bax were upregulated whereas Bcl-2 was downregulated relative to the control group. These effects were reversed by Tβ4 overexpression. Endoplasmic reticulum (ER) stress was observed in the OGD/R group, but this was abolished in neurons overexpressing Tβ4. The protective effect of Tβ4 against OGD/R injury was also demonstrated in cells treated with exogenous Tβ4 (10 ng/mL), which blocked OGD/R-induced apoptosis by inhibiting ER stress-related and pro-apoptotic protein expression. Conclusion: Tβ4 prevents OGD/R-induced ER stress-dependent apoptosis in cortical neurons, and is a potential treatment for cerebral ischemia-reperfusion injury.

Analysis of Secreted Proteins from Prepubertal Ovarian Tissues Exposed In Vitro to Cisplatin and LH

“…Finally, Hist1h1e, another histone mediating exosomal uptake (see above), was detected in CTRL, CIS, and CIS + LH but not in LH alone; it remained stable in CTRL and CIS + LH, variable in CIS, and appeared at 12 h in LH, implying an initial inhibitory action of the hormone not maintained in the presence of CIS. Secreted Hbat1, an isotype of hemoglobin alfa with a potential role as an antioxidant molecule in ovarian follicles [ 20 , 21 ], and Tmsb4x, a member of the thymosin family with a role in preventing apoptosis in certain cell types [ 22 , 23 ], were present in CTRL, LH, and CIS + LH but not in CIS, suggesting inhibition by CIS removed by LH; their presence was, however, variable in all groups at a later time.…”

Inhibition of GPR4 attenuates SH-SY5Y cell injury in cerebral ischemia/reperfusion via anti-apoptotic pathways

“…Cerebral ischemia can cause sudden limitation of limb movement, language and sensory disorders, tissue damage and organ dysfunction, and even infarction of key brain regions (Zhang et al, 2019). In the process of rapid recovery of blood flow to the ischemic tissue, reperfusion injury occurs and causes secondary neuron injury (Ferlito et al, 2014;Caltagirone et al, 2016).…”

“…A study demonstrated that in cortical neuronal injury induced by OGD/R, the expression of CHOP is up-regulated, indicating that the overexpression of CHOP is related to CIRI (Zhang et al, 2019).…”

Progress on the Function and Application of Thymosin β4

“…In oxygen-glucose deprived and reoxygenated (OGD/R) cells, the rate of apoptosis was increased and GRP78, CHOP, and Bax were upregulated; however, Bcl-2 was downregulated, which was reversed by Tb4 overexpression. Moreover, Tb4 prevented OGD/R-induced endoplasmic reticulum stress-dependent apoptosis in cortical neurons (27). As Tb4 could attenuate the OGD/R-associated downregulation of P62 and Bcl-2 as well as the upregulation of autophagy mediators, such as autophagyrelated protein-5 and the ratio of microtubule-associated protein 1 light chain 3, it effectively inhibited PC12 cell apoptosis and autophagy induced by OGD/R (28).…”

“…Tb4 exhibits anti-inflammatory activities in different pathologies (124) and reduces inflammation in the brain (26), liver (27), eye (89), and heart diseases (80). Diverse mechanisms underlying the inflammatory response via Tb4 regulation following injuries are observed (125).…”