Autophagy protects against neural cell death induced by piperidine alkaloids present in Prosopis juliflora (Mesquite)

Prosopis juliflora is a shrub that has been used to feed animals and humans. However, a synergistic action of piperidine alkaloids has been suggested to be responsible for neurotoxic damage observed in animals. We investigated the involvement of programmed cell death (PCD) and autophagy on the mecha...

Full description

Saved in:

Bibliographic Details
Published in:	Anais da Academia Brasileira de Ciências Vol. 89; no. 1; pp. 247 - 261
Main Authors:	Silva, Victor D A, Cuevas, Carlos, Muñoz, Patricia, Villa, Monica, Ahumada-Castro, Ulises, Huenchuguala, Sandro, Santos, Cleonice C Dos, Araujo, Fillipe M DE, Ferreira, Rafael S, Silva, Vanessa B DA, Silva, Juliana H C E, Soares, Érica N, Velozo, Eudes S, Segura-Aguilar, Juan, Costa, Silvia L
Format:	Journal Article
Language:	English
Published:	Brazil Academia Brasileira de Ciências 01-03-2017
Subjects:	Adenosine Triphosphate - analysis Alkaloids - isolation & purification Alkaloids - toxicity Animals autophagy Autophagy - drug effects Autophagy - physiology Cell Death - drug effects Cell Death - physiology Cell Survival - drug effects Cells, Cultured glial cells Membrane Potential, Mitochondrial - drug effects Membrane Potential, Mitochondrial - physiology MULTIDISCIPLINARY SCIENCES Neuroglia - drug effects Neuroglia - physiology neurons piperidine alkaloids Piperidines - isolation & purification Piperidines - toxicity Plant Extracts - toxicity programmed cell death Prosopis - chemistry Prosopis juliflora Rats Rats, Wistar Time Factors glial cells piperidine alkaloids autophagy programmed cell death Prosopis juliflora neurons
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Prosopis juliflora is a shrub that has been used to feed animals and humans. However, a synergistic action of piperidine alkaloids has been suggested to be responsible for neurotoxic damage observed in animals. We investigated the involvement of programmed cell death (PCD) and autophagy on the mechanism of cell death induced by a total extract (TAE) of alkaloids and fraction (F32) from P. juliflora leaves composed majoritary of juliprosopine in a model of neuron/glial cell co-culture. We saw that TAE (30 µg/mL) and F32 (7.5 µg/mL) induced reduction in ATP levels and changes in mitochondrial membrane potential at 12 h exposure. Moreover, TAE and F32 induced caspase-9 activation, nuclear condensation and neuronal death at 16 h exposure. After 4 h, they induced autophagy characterized by decreases of P62 protein level, increase of LC3II expression and increase in number of GFP-LC3 cells. Interestingly, we demonstrated that inhibition of autophagy by bafilomycin and vinblastine increased the cell death induced by TAE and autophagy induced by serum deprivation and rapamycin reduced cell death induced by F32 at 24 h. These results indicate that the mechanism neural cell death induced by these alkaloids involves PCD via caspase-9 activation and autophagy, which seems to be an important protective mechanism.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0001-3765 1678-2690 1678-2690 0001-3765
DOI:	10.1590/0001-3765201720160477