ABSTRACT
Mitochondria are very complex dual membrane organelles in eukaryotic cells. Under physiological conditions, the regeneration and degradation of mitochondria are balanced. When the components of the proteins, lipids and DNA in the organelles are damaged, the steady state of the mitochondria is maintained by means of division, fusion, autophagy and the like, so as to maintain the integrity of the mitochondrial structure and function, which is commonly referred to as a "mitochondrial mass control". Mitochondrial-derived vesicle (MDV) is a newly discovered pathway of mitochondrial quality control, which plays an important role in the early stage of cell stress and helps maintain the stability of mitochondrial function. In this paper, the discovery of MDV, the transport pathway, the choice of goods and the physiological effects on cells are reviewed.
ABSTRACT
<p><b>BACKGROUND</b>Our previous studies have indicated that the beneficial effects of grafting neural stem cells (NSCs) overexpressing glial cell line-derived neurotrophic factor (GDNF) in rats after stroke. However, the underlying mechanisms are highly debatable. In this study, we investigated whether neurogenesis, Akt, and extracellular signal-regulated kinase 1/2 (Erk1/2) signaling were involved in this process.</p><p><b>METHODS</b>Transient ischemic stroke were induced by occluding middle cerebral artery for 2 hours and reperfusion. At 3 days after reperfusion, GDNF/NSCs, NSCs, and vehicle were administered. Immunohistochemical staining was used to evaluate neurogenesis by nestin antibody; phosphorylation of Akt and Erk1/2 was investigated by Western blotting analysis.</p><p><b>RESULTS</b>Transplantation of GDNF/NSCs and NSCs significantly increased nestin-positive cells compared to control group (vehicle) from 1 to 7 weeks after reperfusion, and GDNF/NSCs showed stronger effect than NSCs at 2 and 3 weeks after reperfusion. Meanwhile, enhanced phosphorylation level of Erk1/2 was observed in the GDNF/NSCs and NSCs groups compared with control group, and phosphorylation level of Erk1/2 in GDNF/NSCs group was remarkably higher than that of NSCs group at any given time. In contrast, expression of mitogen-activated protein kinase phosphatase-1 (MKP-1), known as inhibitor of Erk1/2 signaling, was significantly decreased in the GDNF/NSCs and NSCs groups compared with the control group. Moreover, much enhanced and prolonged phosphorylation level of Akt of GDNF/NSCs group was detected compared with control and NSCs group.</p><p><b>CONCLUSION</b>Grafting GDNF/NSCs enhances neurogenesis and activates Akt and Erk1/2 signaling, that may provide the potential for GDNF/NSCs in stroke treatment.</p>