Ca2+-dependent autophagy is enhanced by the pharmacological agent PK11195: Pharmacological tools in autophagy

Annalisa Gastaldello, Holly Callaghan, Priya Gami, Michelangelo Campanella

Research output: Contribution to journalArticle

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 [Ca2+] in the endoplasmic reticulum ([Ca2+] er) as well as IP3 induced mitochondrial ([Ca 2+]m) and cytosolic ([Ca2+]c) Ca2+ 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 Ca2+ dependent (ATP, vitamin D3) and independent (rapamycin and H2O2) 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 H2O2. Notably, Bcl-2 deletion abolished PK11195 effects, thus suggesting a selective way of action against the oncogene. By these means, PK11195 is proposed as a facilitator of Ca2+- mediated autophagy and a tool to ascertain the Bcl-2 contribution to the onset and unfolding of this essential catabolic process for cellular homeostasis.

Original languageEnglish
Pages (from-to)607-613
Number of pages7
JournalAutophagy
Volume6
Issue number5
DOIs
Publication statusPublished - Jul 1 2010

Fingerprint

Autophagy
Pharmacology
Cholecalciferol
Sirolimus
Oncogenes
Adenosine Triphosphate
Cervix Uteri
Endoplasmic Reticulum
PK 11195
Homeostasis
Cell Death
Yeasts
Carcinoma

Keywords

  • Autophagy
  • Bcl-2
  • Ca
  • LC3
  • PK11195

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Ca2+-dependent autophagy is enhanced by the pharmacological agent PK11195 : Pharmacological tools in autophagy. / Gastaldello, Annalisa; Callaghan, Holly; Gami, Priya; Campanella, Michelangelo.

In: Autophagy, Vol. 6, No. 5, 01.07.2010, p. 607-613.

Research output: Contribution to journalArticle

Gastaldello, Annalisa ; Callaghan, Holly ; Gami, Priya ; Campanella, Michelangelo. / Ca2+-dependent autophagy is enhanced by the pharmacological agent PK11195 : Pharmacological tools in autophagy. In: Autophagy. 2010 ; Vol. 6, No. 5. pp. 607-613.
@article{a80ec88ecfa94057a7cc092e7023139a,
title = "Ca2+-dependent autophagy is enhanced by the pharmacological agent PK11195: Pharmacological tools in autophagy",
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 [Ca2+] in the endoplasmic reticulum ([Ca2+] er) as well as IP3 induced mitochondrial ([Ca 2+]m) and cytosolic ([Ca2+]c) Ca2+ 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 Ca2+ dependent (ATP, vitamin D3) and independent (rapamycin and H2O2) 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 H2O2. Notably, Bcl-2 deletion abolished PK11195 effects, thus suggesting a selective way of action against the oncogene. By these means, PK11195 is proposed as a facilitator of Ca2+- mediated autophagy and a tool to ascertain the Bcl-2 contribution to the onset and unfolding of this essential catabolic process for cellular homeostasis.",
keywords = "Autophagy, Bcl-2, Ca, LC3, PK11195",
author = "Annalisa Gastaldello and Holly Callaghan and Priya Gami and Michelangelo Campanella",
year = "2010",
month = "7",
day = "1",
doi = "10.4161/auto.6.5.11964",
language = "English",
volume = "6",
pages = "607--613",
journal = "Autophagy",
issn = "1554-8627",
publisher = "Taylor and Francis Inc.",
number = "5",

}

TY - JOUR

T1 - Ca2+-dependent autophagy is enhanced by the pharmacological agent PK11195

T2 - Pharmacological tools in autophagy

AU - Gastaldello, Annalisa

AU - Callaghan, Holly

AU - Gami, Priya

AU - Campanella, Michelangelo

PY - 2010/7/1

Y1 - 2010/7/1

N2 - 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 [Ca2+] in the endoplasmic reticulum ([Ca2+] er) as well as IP3 induced mitochondrial ([Ca 2+]m) and cytosolic ([Ca2+]c) Ca2+ 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 Ca2+ dependent (ATP, vitamin D3) and independent (rapamycin and H2O2) 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 H2O2. Notably, Bcl-2 deletion abolished PK11195 effects, thus suggesting a selective way of action against the oncogene. By these means, PK11195 is proposed as a facilitator of Ca2+- mediated autophagy and a tool to ascertain the Bcl-2 contribution to the onset and unfolding of this essential catabolic process for cellular homeostasis.

AB - 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 [Ca2+] in the endoplasmic reticulum ([Ca2+] er) as well as IP3 induced mitochondrial ([Ca 2+]m) and cytosolic ([Ca2+]c) Ca2+ 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 Ca2+ dependent (ATP, vitamin D3) and independent (rapamycin and H2O2) 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 H2O2. Notably, Bcl-2 deletion abolished PK11195 effects, thus suggesting a selective way of action against the oncogene. By these means, PK11195 is proposed as a facilitator of Ca2+- mediated autophagy and a tool to ascertain the Bcl-2 contribution to the onset and unfolding of this essential catabolic process for cellular homeostasis.

KW - Autophagy

KW - Bcl-2

KW - Ca

KW - LC3

KW - PK11195

UR - http://www.scopus.com/inward/record.url?scp=77955343273&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955343273&partnerID=8YFLogxK

U2 - 10.4161/auto.6.5.11964

DO - 10.4161/auto.6.5.11964

M3 - Article

C2 - 20431351

AN - SCOPUS:77955343273

VL - 6

SP - 607

EP - 613

JO - Autophagy

JF - Autophagy

SN - 1554-8627

IS - 5

ER -