1. Gelatin Nanostructured Lipid Carriers Incorporating Nerve Growth Factor Inhibit Endoplasmic Reticulum Stress-Induced Apoptosis and Improve Recovery in Spinal Cord Injury.
- Author
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Zhu SP, Wang ZG, Zhao YZ, Wu J, Shi HX, Ye LB, Wu FZ, Cheng Y, Zhang HY, He S, Wei X, Fu XB, Li XK, Xu HZ, and Xiao J
- Subjects
- Animals, Cell Survival drug effects, Disease Models, Animal, Drug Carriers chemistry, Extracellular Signal-Regulated MAP Kinases metabolism, Female, Nanostructures ultrastructure, Nerve Growth Factor therapeutic use, Neurons drug effects, Neurons metabolism, Neuroprotection drug effects, PC12 Cells, Proto-Oncogene Proteins c-akt metabolism, Rats, Rats, Sprague-Dawley, Signal Transduction drug effects, Spinal Cord Injuries drug therapy, Up-Regulation drug effects, Apoptosis drug effects, Endoplasmic Reticulum Stress drug effects, Gelatin chemistry, Lipids chemistry, Nanostructures chemistry, Nerve Growth Factor pharmacology, Recovery of Function drug effects, Spinal Cord Injuries physiopathology
- Abstract
Clinical translation of growth factor therapies faces multiple challenges; the most significant one is the short half-life of the naked protein. Gelatin nanostructured lipid carriers (GNLs) had previously been used to encapsulate the basic fibroblast growth factor to enhance the functional recovery in hemiparkinsonian rats. In this research, we comparatively study the enhanced therapy between nerve growth factor (NGF) loaded GNLs (NGF-GNLs) and NGF only in spinal cord injury (SCI). The effects of NGF-GNLs and NGF only were tested by the Basso-Beattie-Bresnahan (BBB) locomotion scale, inclined plane test, and footprint analysis. Western blot analysis and immunofluorescent staining were further performed to identify the expression of ER stress-related proteins, neuron-specific marker neuronal nuclei (NeuN), and growth-associated protein 43 (GAP43). Correlated downstream signals Akt/GSK-3β and ERK1/2 were also analyzed with or without inhibitors. Results showed that NGF-GNLs, compared to NGF only, enhanced the neuroprotection effect in SCI rats. The ER stress-induced apoptosis response proteins CHOP, GRP78 and caspase-12 inhibited by NGF-GNL treatment were more obvious. Meanwhile, NGF-GNLs in the recovery of SCI are related to the inhibition of ER stress-induced cell death via the activation of downstream signals PI3K/Akt/GSK-3β and ERK1/2.
- Published
- 2016
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