Autophagy is activated in compression-induced cell degeneration and is mediated by reactive oxygen species in nucleus pulposus cells exposed to compression.

Abstract:

OBJECTIVE:To determine whether autophagy contributes to the pathogenesis of degenerative disc disease (DDD) or retards the intervertebral disc (IVD) degeneration, and investigate the possible relationship between compression-induced autophagy and intracellular reactive oxygen species (ROS) in nucleus pulposus (NP) cells in vitro. METHODS:The autophagosome and autophagy-related markers were used to explore the role of autophagy in rat NP cells under compressive stress, which were measured directly by electronic microscopy, monodansylcadaverine (MDC) staining, immunofluorescence, western blot, and indirectly by analyzing the impact of pharmacological inhibitors of autophagy such as 3-methyladenine (3-MA) and chloroquine (CQ). And the relationship between autophagy and apoptosis was investigated by Annexin-V/propidium iodide (PI)-fluorescein staining. In addition, ROS were measured to determine whether these factors are responsible for the development of compression-induced autophagy. RESULTS:Our results indicated that rat NP cells activated autophagy in response to the same strong apoptotic stimuli that triggered apoptosis by compression. Autophagy and apoptosis were interconnected and coordinated in rat NP cells exposed to compression stimuli. Compression-induced autophagy was closely related to intracellular ROS production. CONCLUSIONS:Enhanced degradation of damaged components of NP cells by autophagy may be a crucial survival response against mechanical overload, and extensive autophagy may trigger autophagic cell death. Regulating autophagy and reducing the generation of intracellular ROS may retard IVD degeneration.

authors

Ma KG,Shao ZW,Yang SH,Wang J,Wang BC,Xiong LM,Wu Q,Chen SF

doi

10.1016/j.joca.2013.10.002

subject

Has Abstract

pub_date

2013-12-01 00:00:00

pages

2030-8

issue

12

eissn

1063-4584

issn

1522-9653

pii

S1063-4584(13)00973-4

journal_volume

21

pub_type

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