'How can I halt thee?' The puzzles involved in autophagic inhibition.
Pharmacol Res
; 82: 1-8, 2014 Apr.
Article
em En
| MEDLINE
| ID: mdl-24657238
The strategy for interpreting the role of autophagy on the basis of evidence obtained through autophagic inhibition sounds logical, but is beset with practical constraints. The knock down of autophagy-related (ATG) gene(s) or blockage of class III PI3-Kinase are the most common approaches for inhibiting autophagy. However, during stressful conditions, autophagy may operate in synchrony with other processes such as apoptosis; autophagy-related genes, unlike what their name implies, exert their regulation on apoptosis as well. Knocking down such genes not only blocks autophagy but also renders apoptosis defective, making the interpretation of autophagic roles unreliable. Similarly, class III PI3-Kinase aids in initiating autophagy but it is not a quintessential autophagic regulator. Class III PI3-Kinase also has a role in regulating almost all membrane transport in cells. Blocking it not only inhibits autophagy, but also hampers all the membrane trades, including endosomal transport. The pharmacological inhibitors used to block autophagy by blocking class III PI3-Kinase further compound these limitations with their off-target effects. Knowing the limitations involved in blocking a target or using an autophagy-blocking tool is a prerequisite for designing the experiments meant for analyzing autophagic functions. This review attempts to provide a detailed overview about the practical constraints involved in using autophagic inhibition as a strategy to understand autophagy.
Palavras-chave
3-Methyladenine; 3-Methyladenine (PubChem CID: 1673); Ammonium chloride (PubChem CID: 25517); Apoptosis; Atg5; Autophagy; Bafilomycin A1 (PubChem CID: 6436223); Beclin1; Chloroquine (PubChem CID: 2719); E64d (PubChem CID: 393035); KU55933 (PubChem CID: 5278396); Monensin (PubChem CID: 28263); Wortmannin (PubChem CID: 312145)
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Inibidores de Fosfoinositídeo-3 Quinase
Limite:
Animals
Idioma:
En
Revista:
Pharmacol Res
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Índia