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Ca 2+ -dependent autophagy is enhanced by the pharmacological agent PK11195

Ca 2+ -dependent autophagy is enhanced by the pharmacological agent PK11195
Ca 2+ -dependent autophagy is enhanced by the pharmacological agent PK11195
The 1-(2-Chlorophenyl-N-methylpropyl)-3-isoquinolinecarboxamide, PK11195, is a proven enhancer of apoptotic cell death in a variety of cellular models. Recently, we have shown that by targeting the oncogene Bcl-2, PK11195 increases the [Ca ( 2+) ] in the Endoplasmic Reticulum ([Ca ( 2+) ]er) as well as IP3 induced mitochondrial ([Ca ( 2+) ]m) and cytosolic ([Ca ( 2+) ]c) Ca ( 2+) transients in HeLa cervix carcinoma cells. Here, in the same cells, we have investigated PK11195 contribution to models of pharmacologically induced macroautophagy. To do so, we have monitored the pattern of LC3 (the mammalian orthologue of yeast Atg8) distribution and post transcriptional modifications after challenging with Ca ( 2+) -dependent (ATP, Vitamin D3) and independent (Rapamycin and H 2O 2) stimuli for autophagy execution. We found that PK11195 plays a pro-autophagy role if associated with ATP and Vitamin D3 to be ineffective if co-incubated with Rapamycin and H 2O 2. Notably, Bcl-2 deletion abolished PK11195 effects thus suggesting a selective way of action against the oncogene. By these means, PK11195 is proposed as facilitator of Ca ( 2+) mediated autophagy and tool to ascertain the Bcl-2 contribution to the onset and unfolding of this essential catabolic process for cellular homeostasis.
1554-8627
607-613
Gastaldello, Annallisa
ac4979bd-1e44-4783-ba03-1f4f5934f1c6
Callaghan, Holly
25e2a3d4-8c5f-4c1b-923b-5faea0ea3921
Gami, Priya
8568b0ef-cbb0-4439-bb36-aa85116b8ffb
Campanella, Michelangelo
66eb8a82-8584-4b59-b041-85b429f0d87c
Gastaldello, Annallisa
ac4979bd-1e44-4783-ba03-1f4f5934f1c6
Callaghan, Holly
25e2a3d4-8c5f-4c1b-923b-5faea0ea3921
Gami, Priya
8568b0ef-cbb0-4439-bb36-aa85116b8ffb
Campanella, Michelangelo
66eb8a82-8584-4b59-b041-85b429f0d87c

Gastaldello, Annallisa, Callaghan, Holly, Gami, Priya and Campanella, Michelangelo (2010) Ca 2+ -dependent autophagy is enhanced by the pharmacological agent PK11195. Autophagy, 6 (5), 607-613. (doi:10.4161/auto.6.5.11964). (PMID:20431351)

Record type: Article

Abstract

The 1-(2-Chlorophenyl-N-methylpropyl)-3-isoquinolinecarboxamide, PK11195, is a proven enhancer of apoptotic cell death in a variety of cellular models. Recently, we have shown that by targeting the oncogene Bcl-2, PK11195 increases the [Ca ( 2+) ] in the Endoplasmic Reticulum ([Ca ( 2+) ]er) as well as IP3 induced mitochondrial ([Ca ( 2+) ]m) and cytosolic ([Ca ( 2+) ]c) Ca ( 2+) transients in HeLa cervix carcinoma cells. Here, in the same cells, we have investigated PK11195 contribution to models of pharmacologically induced macroautophagy. To do so, we have monitored the pattern of LC3 (the mammalian orthologue of yeast Atg8) distribution and post transcriptional modifications after challenging with Ca ( 2+) -dependent (ATP, Vitamin D3) and independent (Rapamycin and H 2O 2) stimuli for autophagy execution. We found that PK11195 plays a pro-autophagy role if associated with ATP and Vitamin D3 to be ineffective if co-incubated with Rapamycin and H 2O 2. Notably, Bcl-2 deletion abolished PK11195 effects thus suggesting a selective way of action against the oncogene. By these means, PK11195 is proposed as facilitator of Ca ( 2+) mediated autophagy and tool to ascertain the Bcl-2 contribution to the onset and unfolding of this essential catabolic process for cellular homeostasis.

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Published date: July 2010
Organisations: Centre for Biological Sciences

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Local EPrints ID: 382909
URI: http://eprints.soton.ac.uk/id/eprint/382909
ISSN: 1554-8627
PURE UUID: b3722c1b-3100-4235-9512-a142c476534b

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Date deposited: 04 Nov 2015 11:46
Last modified: 15 Jul 2019 21:01

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