Pharmacological inhibition of mTORC1 activity protects against inflammation-induced apoptosis of nucleus pulposus cells
Rev. bras. pesqui. méd. biol
; Braz. j. med. biol. res;54(5): e10185, 2021. graf
Article
em En
| LILACS
| ID: biblio-1153547
Biblioteca responsável:
BR1.1
ABSTRACT
Lumbar disc herniation is a common disease characterized by the degeneration of intervertebral discs (IVDs), accompanied by imbalance of metabolic and inflammatory homeostasis. Current studies establish that IVD degeneration is induced by increased apoptosis of nucleus pulposus (NP) cells. However, the underlying mechanisms of NP cell survival/apoptosis are not well elucidated. Here, we reveal a novel mechanism by which mTORC1 signaling controls NP cell survival through regulating metabolic homeostasis. We demonstrated that hyperactivated mTORC1 activity induced by inflammatory cytokines engenders the apoptosis of NP cells, whereas pharmacological inhibition of mTORC1 activity promotes NP cell survival. Using an integrative approach spanning metabolomics and biochemical approaches, we showed that mTORC1 activation enhanced glucose metabolism and lactic acid production, and therefore caused NP cell apoptosis. Our study identified mTORC1 in NP cells as a novel target for IVD degeneration, and provided potential strategies for clinical intervention of lumbar disc herniation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
LILACS
Assunto principal:
Degeneração do Disco Intervertebral
/
Núcleo Pulposo
Limite:
Humans
Idioma:
En
Revista:
Braz. j. med. biol. res
/
Rev. bras. pesqui. méd. biol
Assunto da revista:
BIOLOGIA
/
MEDICINA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Brasil