A miRNA-101-3p/Bim axis as a determinant of serum deprivation-induced endothelial cell apoptosis

Ji Hee Kim, Dong Keon Lee, Joohwan Kim, Seunghwan Choi, Wonjin Park, Kwon Soo Ha, Tae Hoon Kim, Jongseon Choe, Moo Ho Won, Young Guen Kwon, Young Myeong Kim

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Serum deprivation or withdrawal induces apoptosis in endothelial cells, resulting in endothelial cell dysfunction that is associated with cardiovascular disease. However, there is still limited information on the role of miRNA in serum deprivation-induced apoptosis. Here we found that serum deprivation increased caspase-dependent apoptosis through miRNA-101-3p downregulation, without altering expression of its host gene RNA 3'-terminal phosphate cyclase-like 1, which was highly correlated with suppressed expression levels of Dicer and Argonaute 2 (Ago2), indicating that miR-101-3p is post-transcriptionally elevated in serum-deprived conditions. The decreased miR-101-3p caused elevated Bim expression by targeting its 3'-untranslated region (3'-UTR). This resulted in activation of the intrinsic pathway of apoptosis via interaction with Bcl-2, decreased mitochondrial membrane potential, cytochrome c release, mitochondrial reactive oxygen species (ROS) production, and caspase activation. These events were abrogated by miR-101-3p mimic and the proapoptotic Bim siRNA, which suggest a determinant role of the miR-101-3p/Bim axis in serum deprivation-induced apoptosis. The apoptosis induced by miR-101-3p-mediated Bim expression is mediated by both caspase-3 and -1, which are activated by two distinct intrinsic mechanisms, cytochrome c release and ROS-induced inflammasome activation, respectively. In other words, the antioxidant inhibited endothelial cell death mediated by caspase-1 that activated caspase-7, but not caspase-3. These findings provide mechanistic insight into a novel function of miR-101-3p in serum withdrawal-induced apoptosis triggered by activating two different intrinsic or mitochondrial apoptosis pathways, implicating miR-101-3p as a therapeutic target that limits endothelial cell death associated with vascular disorders.

Original languageEnglish
Pages (from-to)e2808
JournalCell death & disease
Volume8
Issue number5
DOIs
Publication statusPublished - 2017 May 18

Fingerprint

MicroRNAs
Endothelial Cells
Apoptosis
Serum
Caspase 1
Caspases
Cytochromes c
Caspase 3
Reactive Oxygen Species
Cell Death
Inflammasomes
Caspase 7
Mitochondrial Membrane Potential
3' Untranslated Regions
Small Interfering RNA
Blood Vessels
Cardiovascular Diseases
Down-Regulation
Antioxidants
Genes

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Cite this

Kim, J. H., Lee, D. K., Kim, J., Choi, S., Park, W., Ha, K. S., ... Kim, Y. M. (2017). A miRNA-101-3p/Bim axis as a determinant of serum deprivation-induced endothelial cell apoptosis. Cell death & disease, 8(5), e2808. https://doi.org/10.1038/cddis.2017.219
Kim, Ji Hee ; Lee, Dong Keon ; Kim, Joohwan ; Choi, Seunghwan ; Park, Wonjin ; Ha, Kwon Soo ; Kim, Tae Hoon ; Choe, Jongseon ; Won, Moo Ho ; Kwon, Young Guen ; Kim, Young Myeong. / A miRNA-101-3p/Bim axis as a determinant of serum deprivation-induced endothelial cell apoptosis. In: Cell death & disease. 2017 ; Vol. 8, No. 5. pp. e2808.
@article{e35159f8feb64b13a424c66c3bfd75df,
title = "A miRNA-101-3p/Bim axis as a determinant of serum deprivation-induced endothelial cell apoptosis",
abstract = "Serum deprivation or withdrawal induces apoptosis in endothelial cells, resulting in endothelial cell dysfunction that is associated with cardiovascular disease. However, there is still limited information on the role of miRNA in serum deprivation-induced apoptosis. Here we found that serum deprivation increased caspase-dependent apoptosis through miRNA-101-3p downregulation, without altering expression of its host gene RNA 3'-terminal phosphate cyclase-like 1, which was highly correlated with suppressed expression levels of Dicer and Argonaute 2 (Ago2), indicating that miR-101-3p is post-transcriptionally elevated in serum-deprived conditions. The decreased miR-101-3p caused elevated Bim expression by targeting its 3'-untranslated region (3'-UTR). This resulted in activation of the intrinsic pathway of apoptosis via interaction with Bcl-2, decreased mitochondrial membrane potential, cytochrome c release, mitochondrial reactive oxygen species (ROS) production, and caspase activation. These events were abrogated by miR-101-3p mimic and the proapoptotic Bim siRNA, which suggest a determinant role of the miR-101-3p/Bim axis in serum deprivation-induced apoptosis. The apoptosis induced by miR-101-3p-mediated Bim expression is mediated by both caspase-3 and -1, which are activated by two distinct intrinsic mechanisms, cytochrome c release and ROS-induced inflammasome activation, respectively. In other words, the antioxidant inhibited endothelial cell death mediated by caspase-1 that activated caspase-7, but not caspase-3. These findings provide mechanistic insight into a novel function of miR-101-3p in serum withdrawal-induced apoptosis triggered by activating two different intrinsic or mitochondrial apoptosis pathways, implicating miR-101-3p as a therapeutic target that limits endothelial cell death associated with vascular disorders.",
author = "Kim, {Ji Hee} and Lee, {Dong Keon} and Joohwan Kim and Seunghwan Choi and Wonjin Park and Ha, {Kwon Soo} and Kim, {Tae Hoon} and Jongseon Choe and Won, {Moo Ho} and Kwon, {Young Guen} and Kim, {Young Myeong}",
year = "2017",
month = "5",
day = "18",
doi = "10.1038/cddis.2017.219",
language = "English",
volume = "8",
pages = "e2808",
journal = "Cell Death and Disease",
issn = "2041-4889",
publisher = "Nature Publishing Group",
number = "5",

}

Kim, JH, Lee, DK, Kim, J, Choi, S, Park, W, Ha, KS, Kim, TH, Choe, J, Won, MH, Kwon, YG & Kim, YM 2017, 'A miRNA-101-3p/Bim axis as a determinant of serum deprivation-induced endothelial cell apoptosis', Cell death & disease, vol. 8, no. 5, pp. e2808. https://doi.org/10.1038/cddis.2017.219

A miRNA-101-3p/Bim axis as a determinant of serum deprivation-induced endothelial cell apoptosis. / Kim, Ji Hee; Lee, Dong Keon; Kim, Joohwan; Choi, Seunghwan; Park, Wonjin; Ha, Kwon Soo; Kim, Tae Hoon; Choe, Jongseon; Won, Moo Ho; Kwon, Young Guen; Kim, Young Myeong.

In: Cell death & disease, Vol. 8, No. 5, 18.05.2017, p. e2808.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A miRNA-101-3p/Bim axis as a determinant of serum deprivation-induced endothelial cell apoptosis

AU - Kim, Ji Hee

AU - Lee, Dong Keon

AU - Kim, Joohwan

AU - Choi, Seunghwan

AU - Park, Wonjin

AU - Ha, Kwon Soo

AU - Kim, Tae Hoon

AU - Choe, Jongseon

AU - Won, Moo Ho

AU - Kwon, Young Guen

AU - Kim, Young Myeong

PY - 2017/5/18

Y1 - 2017/5/18

N2 - Serum deprivation or withdrawal induces apoptosis in endothelial cells, resulting in endothelial cell dysfunction that is associated with cardiovascular disease. However, there is still limited information on the role of miRNA in serum deprivation-induced apoptosis. Here we found that serum deprivation increased caspase-dependent apoptosis through miRNA-101-3p downregulation, without altering expression of its host gene RNA 3'-terminal phosphate cyclase-like 1, which was highly correlated with suppressed expression levels of Dicer and Argonaute 2 (Ago2), indicating that miR-101-3p is post-transcriptionally elevated in serum-deprived conditions. The decreased miR-101-3p caused elevated Bim expression by targeting its 3'-untranslated region (3'-UTR). This resulted in activation of the intrinsic pathway of apoptosis via interaction with Bcl-2, decreased mitochondrial membrane potential, cytochrome c release, mitochondrial reactive oxygen species (ROS) production, and caspase activation. These events were abrogated by miR-101-3p mimic and the proapoptotic Bim siRNA, which suggest a determinant role of the miR-101-3p/Bim axis in serum deprivation-induced apoptosis. The apoptosis induced by miR-101-3p-mediated Bim expression is mediated by both caspase-3 and -1, which are activated by two distinct intrinsic mechanisms, cytochrome c release and ROS-induced inflammasome activation, respectively. In other words, the antioxidant inhibited endothelial cell death mediated by caspase-1 that activated caspase-7, but not caspase-3. These findings provide mechanistic insight into a novel function of miR-101-3p in serum withdrawal-induced apoptosis triggered by activating two different intrinsic or mitochondrial apoptosis pathways, implicating miR-101-3p as a therapeutic target that limits endothelial cell death associated with vascular disorders.

AB - Serum deprivation or withdrawal induces apoptosis in endothelial cells, resulting in endothelial cell dysfunction that is associated with cardiovascular disease. However, there is still limited information on the role of miRNA in serum deprivation-induced apoptosis. Here we found that serum deprivation increased caspase-dependent apoptosis through miRNA-101-3p downregulation, without altering expression of its host gene RNA 3'-terminal phosphate cyclase-like 1, which was highly correlated with suppressed expression levels of Dicer and Argonaute 2 (Ago2), indicating that miR-101-3p is post-transcriptionally elevated in serum-deprived conditions. The decreased miR-101-3p caused elevated Bim expression by targeting its 3'-untranslated region (3'-UTR). This resulted in activation of the intrinsic pathway of apoptosis via interaction with Bcl-2, decreased mitochondrial membrane potential, cytochrome c release, mitochondrial reactive oxygen species (ROS) production, and caspase activation. These events were abrogated by miR-101-3p mimic and the proapoptotic Bim siRNA, which suggest a determinant role of the miR-101-3p/Bim axis in serum deprivation-induced apoptosis. The apoptosis induced by miR-101-3p-mediated Bim expression is mediated by both caspase-3 and -1, which are activated by two distinct intrinsic mechanisms, cytochrome c release and ROS-induced inflammasome activation, respectively. In other words, the antioxidant inhibited endothelial cell death mediated by caspase-1 that activated caspase-7, but not caspase-3. These findings provide mechanistic insight into a novel function of miR-101-3p in serum withdrawal-induced apoptosis triggered by activating two different intrinsic or mitochondrial apoptosis pathways, implicating miR-101-3p as a therapeutic target that limits endothelial cell death associated with vascular disorders.

UR - http://www.scopus.com/inward/record.url?scp=85028978904&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85028978904&partnerID=8YFLogxK

U2 - 10.1038/cddis.2017.219

DO - 10.1038/cddis.2017.219

M3 - Article

C2 - 28518140

AN - SCOPUS:85028978904

VL - 8

SP - e2808

JO - Cell Death and Disease

JF - Cell Death and Disease

SN - 2041-4889

IS - 5

ER -