Coordinated activation of AMP-activated protein kinase, extracellular signal-regulated kinase, and autophagy regulates phorbol myristate acetate-induced differentiation of SH-SY5Y neuroblastoma cells
2015
Аутори:
Zogović, NevenaTovilović-Kovačević, Gordana
Misirkić Marjanović, Maja
Vučićević, Ljubica
Janjetović, Kristina
Harhaji-Trajković, Ljubica
Trajkovic, Vladimir
Тип документа:
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт:
We explored the interplay between the intracellular energy sensor
AMP-activated protein kinase (AMPK), extracellular signal-regulated
kinase (ERK), and autophagy in phorbol myristate acetate (PMA)-induced
neuronal differentiation of SH-SY5Y human neuroblastoma cells.
PMA-triggered expression of neuronal markers (dopamine transporter,
microtubule-associated protein 2, -tubulin) was associated with an
autophagic response, measured by the conversion of
microtubule-associated protein light chain 3 (LC3)-I to
autophagosome-bound LC3-II, increase in autophagic flux, and expression
of autophagy-related (Atg) proteins Atg7 and beclin-1. This coincided
with the transient activation of AMPK and sustained activation of ERK.
Pharmacological inhibition or RNA interference-mediated silencing of
AMPK suppressed PMA-induced expression of neuronal markers, as well as
ERK activation and autophagy. A selective pharmacological blockade of
ERK prevented PMA-induced neuronal differentiation and autophagy
induction without affecting AMPK phosphorylation. Conversely, the
inhibition of autophagy downstream of AMPK/ERK, either by
pharmacological agents or LC3 knockdown, promoted the expression of
neuronal markers, thus indicating a role of autophagy in the suppression
of PMA-induced differentiation of SH-SY5Y cells. Therefore, PMA-induced
neuronal differentiation of SH-SY5Y cells depends on a complex interplay
between AMPK, ERK, and autophagy, in which the stimulatory effects of
AMPK/ERK signaling are counteracted by the coinciding autophagic
response.
Кључне речи:
autophagy; extracellular signal-regulated kinase; neuronal differentiation; phorbol myristate acetateИзвор:
Journal of Neurochemistry, 2015, 133, 2, 223-232
DOI: 10.1111/jnc.12980
ISSN: 1471-4159