Piperlongumine restores the balance of autophagy and apoptosis by increasing BCL2 phosphorylation in rotenone-induced Parkinson disease models
AUTOPHAGY
Authors: Liu, Jia; Liu, Weijin; Lu, Yongquan; Tian, Hao; Duan, Chunli; Lu, Lingling; Gao, Ge; Wu, Xia; Wang, Xiaomin; Yang, Hui
Abstract
Parkinson disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease and is caused by genetics, environmental factors and aging, with few treatments currently available. Apoptosis and macroautophagy/autophagy play critical roles in PD pathogenesis; as such, modulating their balance is a potential treatment strategy. BCL2 (B cell leukemia/lymphoma 2) is a key molecule regulating this balance. Piperlongumine (PLG) is an alkaloid extracted from Piper longum L. that has antiinflammatory and anticancer effects. The present study investigated the protective effects of PLG in rotenone-induced PD cell and mouse models. We found that PLG administration (2 and 4 mg/kg) for 4 wk attenuated motor deficits in mice and prevented the loss of dopaminergic neurons in the substantia nigra induced by oral administration of rotenone (10 mg/kg) for 6 wk. PLG improved cell viability and enhanced mitochondrial function in primary neurons and SK-N-SH cells. These protective effects were exerted via inhibition of apoptosis and induction of autophagy through enhancement of BCL2 phosphorylation at Ser70. These results demonstrate that PLG exerts therapeutic effects in a rotenone-induced PD models by restoring the balance between apoptosis and autophagy.
Cell proliferation influenced by matrix compliance of gelatin grafted poly(D,L-Lactide) three dimensional scaffolds
COLLOIDS AND SURFACES B-BIOINTERFACES
Authors: Balavigneswaran, Chelladurai Karthikeyan; Mahto, Sanjeev Kumar; Mahanta, Arun Kumar; Singh, Rajshree; Vijayakumar, Mahalingam Rajamanickam; Ray, Biswajit; Misra, Nira
Abstract
Surface and mechanical properties of the biomaterials are determinants of cellular responses. In our previous study, star-shaped poly(D,L-Lactide)-b-gelatin (ss-pLG) was reported for possessing improved cellular adhesion and proliferation. Here, we extended our investigation to establish the cellular compatibility of gelatin-grafted PDLLA with respect to mechanical properties of biological tissues. In this view, linear PDLLA-b-gelatin (l-pLG) was synthesized and tissue-level compatibility of 1-pLG and ss-pLG against fibroblasts (L929), myoblasts (C2C12) and preosteoblasts (MG-63) was examined. The cell proliferation of C2C12 was significantly higher within 1-pLG scaffolds, whereas L929 showed intensified growth within ss-pLG scaffolds. The difference in cell proliferation may be attributed to the varying mechanical properties of scaffolds; where the stiffness of 1-pLG scaffolds was notably higher than ss-pLG scaffolds, most likely due to the variable levels of gelatin grafting on the backbone of PDLLA. Therefore, gelatin grafting can be used to modulate mechanical property of the scaffolds and this study reveals the significance of the matrix stiffness to produce the successful 3D scaffolds for tissue engineering applications. (C) 2018 Elsevier B.V. All rights reserved.