Role of ATG 5 in ER stress-induced apoptosis in meniscus.

Osteoarthritis (OA) is a degenerative disorder of the whole joint that affects 23 million older adults in the US. Obesity, one of the major risk factor for OA, is associated with increased circulating free fatty acids (FFAs). The overall objective of this project was to examine the effect of these FFAs in meniscus joint tissues. Our study demonstrated that saturated free fatty acid palmitate induces endoplasmic reticulum stress in primary porcine meniscus cells, and significantly decreased the protein level of ATG 5, a major autophagy related protein involved in autophagosome formation. Downregulation of ATG 5 protein levels was associated with decreased lipidation of LC3 and increased activation of Cleaved Caspase 3, which promoted meniscus cell apoptosis. Pretreatment of meniscus cells with 4-phenyl butyric acid (PBA), a small molecule chemical chaperone that alleviates ER stress or with MG-132, a proteasome inhibitor, restored normal levels of ATG 5. Taken together our data suggest that FFA palmitate induces ER stress in meniscus cells, decreases autophagy and promotes cell death. This is the first study to demonstrate that ER stress promotes cell death via downregulating autophagy.

Grantor dc:publisher

Wake Forest University

Year dc:date.issued

2017

Author dc:creator

• Mallik, Aritra

Language dc:language.iso

en

Handle dc:identifier.uri

http://hdl.handle.net/10339/82206

OAI identifier oai:identifier

oai:wakespace.lib.wfu.edu:10339/82206