Parkinson’s disease (PD) is an age-related neurodegenerative disease (NDD) characterized by the degenerative loss of dopaminergic neurons in the substantia nigra along with aggregation of α-synuclein (α-syn). Neurogenic differentiation of human adipose-derived stem cells (NI-hADSCs) by supplementary factors for 14 days activates different biological signaling pathways. In this study, we evaluated the therapeutic role of NI-hADSC-conditioned medium (NI-hADSC-CM) in rotenone (ROT)-induced toxicity in SH-SY5Y cells. Increasing concentrations of ROT led to decreased cell survival at 24 and 48 h in a dose- and time-dependent manner. Treatment of NI-hADSC-CM (50% dilution in DMEM) against ROT (0.5 μM) significantly increased the cell survival. ROT toxicity decreased the expression of tyrosine hydroxylase (TH). Western blot analysis of the Triton X-100-soluble fraction revealed that ROT significantly decreased the oligomeric, dimeric, and monomeric phosphorylated Serine129 (p-S129) α-syn, as well as the total monomeric α-syn expression levels. ROT toxicity increased the oligomeric, but decreased the dimeric and monomeric p-S129 α-syn expression levels. Total α-syn expression (in all forms) was increased in the Triton X-100-insoluble fraction, compared to the control. NI-hADSC-CM treatment enhanced the TH expression, stabilized α-syn monomers, reduced the levels of toxic insoluble p-S129 α-syn, improved the expression of neuronal functional proteins, regulated the Bax/Bcl-2 ratio, and upregulated the expression of pro-caspases, along with PARP-1 inactivation. Moreover, hADSC-CM treatment decreased the cell numbers and have no effect against ROT toxicity on SH-SY5Y cells. The therapeutic effects of NI-hADSC-CM was higher than the beneficial effects of hADSC-CM on cellular signaling. From these results, we conclude that NI-hADSC-CM exerts neuroregenerative effects on ROT-induced PD-like impairments in SH-SY5Y cells.
Mesenchymal stem cells (MSCs) have been used against several diseases. Their potential mainly appears from its secreted biomolecules. Human bone marrow-derived stem cells (hBMSC) displayed neuronal functional characteristics after differentiation by basic fibroblast growth factor (bFGF) and forskolin. PD is a chronic age-related neurodegenerative disease (NDD) characterized by loss of dopaminergic neurons in the substantia nigra (SN) and abnormal accumulation of α-synuclein (α-syn) aggregations. In this present study, we evaluated the therapeutic effects of neural differentiated hBMSC (NI-hBMSC) conditioned medium (NI-hBMSC-CM) to a rotenone- (ROT-) induced Parkinson’s disease (PD) model in SH-SY5Y cells. NI-hBMSC-CM treatment (50% diluted) in the last 24 h of 48 h ROT (0.5 μM) toxicity showed a significant increase in cell survival. The decreased tyrosine hydroxylase (TH) expression as a hallmark of PD was increased by NI-hBMSC-CM. The Triton X-100-soluble and Triton X-100-insoluble cell lysate fractions were used in Western blotting. The oligomeric, dimeric, and monomeric phosphorylated serine129 (p-S129) α-syn and total monomeric α-syn were decreased during ROT toxicity in the Triton X-100-soluble fraction. The Triton X-100-insoluble fraction revealed that ROT toxicity significantly increased the oligomeric but decreased the dimeric and monomeric p-S129 α-syn expressions while all forms of total α-syn were increased in SH-SY5Y cells. NI-hBMSC-CM stabilized the physiological α-syn monomers and reduced aggregated insoluble p-S129 α-syn against ROT. The cytoskeletal proteins, neurofilament-H (NF-H), β3-tubulin (Tuj1), neuronal nuclei (NeuN), and synaptophysin (SYP) were significantly decreased during ROT toxicity. In addition, proapoptotic Bax was increased by ROT with decreased antiapoptotic Bcl-2 and Mcl-1 as well as proforms of caspase-9, caspase-3, caspase-7, and PARP-1. NI-hBMSC-CM ameliorated the neurotrophic protein expressions, controlled the Bax/Bcl-2 ratio, upregulated procaspases, and inactivated PARP-1. From our results, we conclude that NI-hBMSC-CM containing released biomolecules during neural differentiation employs regenerative effects on the ROT model of PD in SH-SY5Y cells.
Insulin is a peptide hormone of the endocrine pancreas and exerts a wide variety of physiological actions in insulin sensitive tissues, such as regulation of glucose homeostasis, cell growth, differentiation, learning and memory. However, the role of insulin in osteoblast cells remains to be fully characterized. In this study, we demonstrated that the insulin (100 nM) has the ability to stimulate the phosphorylation of protein kinase B (Akt/PKB) and extracellular signal-regulated kinase (ERK) and the levels of inhibin-βE in the osteoblast-like UMR-106 cells. This insulin-stimulated activities were abolished by the PI3K and MEK1 inhibitors LY294002 and PD98059, respectively. This is the first report proving that insulin is a potential candidate that enables the actions of inhibin-βE subunit of the TGF-β family. The current investigation provides a foundation for the realization of insulin as a potential stimulator in survival signaling pathways in osteoblast-like UMR-106 cells.
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