cytochrome-c-t and apelin-13-peptide

We investigated the effect of apelin-13 on the cellular model of AD, amyloid-β (Aβ) treated SH-SY5Y cells in rats.. The SH-SY5Y cells were pretreated with different doses of apelin-13 (1, 2.5, 5, and 10 μg/mL), half an hour before adding 50% Aβ treatment. After 24 h, cells were evaluated for survival, oxidative stress, mitochondrial calcium release, caspase-3, and cytochrome. Apelin-13 at the dose of 2.5 μg/mL protected against IC50 Aβ (p<0.001). Apelin-13 at doses of 1, 2.5, and 5 μg/mL showed protective effects against the reactive oxygen species (ROS) produced by Aβ (p<0.001). Apelin-13 at doses of 2.5 and 5 μg/mL reduced calcium release, caspase-3, and cytochrome. Apelin-13 prevented apoptosis, oxidative stress, and mitochondrial toxicity and can be a suitable option for treatment of AD. The appropriate treatment strategy for humans has to be investigated in future studies.

Topics: Actins; Amyloid beta-Peptides; Animals; Antioxidants; Apoptosis; Calcium; Caspase 3; Cell Line, Tumor; Cell Survival; Cytochromes c; Humans; Intercellular Signaling Peptides and Proteins; Neuroblastoma; Neuroprotective Agents; Oxidative Stress; Peptide Fragments; Rats; Reactive Oxygen Species

Bone marrow-derived mesenchymal stem cells (BMSCs) have shown great promise for ischemic tissue repair. However, poor viability of transplanted BMSCs within ischemic tissues has limited their therapeutic potential. Apelin, an endogenous peptide, whose level is elevated following ischemia, has been shown to enhance survival of cardiomyocytes and neuronal cells during ischemia. We hypothesized that apelin-13 protects BMSCs from apoptotic death. In this paper we determined the potential mechanism of apelin-13 effects using cultured BMSCs from adult rats. Apoptosis was induced by the specific apoptotic insult serum deprivation (SD) for up to 36 h. Apoptotic cell death was measured using immunostaining and Western blotting in the presence and absence of apelin-13 (0.1 to 5.0 nM) co-applied during SD exposure. SD-induced apoptosis was significantly reduced by apelin-13 in a concentration-dependent manner. SD-induced mitochondrial depolarization, cytochrome c release, and caspase-3 activation were largely prevented by apelin-13. The apelin-13 anti-apoptotic effects were blocked by inhibiting the MAPK/ERK1/2 and PI3K/Akt signaling pathways. Taken together, our findings indicate that apelin-13 is a survival factor for BMSCs and its anti-apoptotic property may prove to be of therapeutic significance in terms of exploiting BMSC-based transplantation therapy.

Topics: Animals; Apelin Receptors; Apoptosis; Caspase 3; Cells, Cultured; Culture Media, Serum-Free; Cytochromes c; Intercellular Signaling Peptides and Proteins; Mesenchymal Stem Cells; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinase Kinases; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Reactive Oxygen Species; Receptors, G-Protein-Coupled; Signal Transduction