Abstract
Our previous studies showed that nitric oxide (NO) could induce osteoblast apoptosis. MicroRNA-1 (miR-1), a skeletal-and cardiac muscle-specific small non-coding RNA, contributes to the regulation of multiple cell activities. In this study, we evaluated the roles of miR-1 in NO-induced insults to osteoblasts and the possible mechanisms. Exposure of mouse MC3T3-E1 cells to sodium nitroprusside (SNP) increased amounts of cellular NO and intracellular reactive oxygen species. Sequentially, SNP decreased cell survival but induced caspase-3 activation, DNA fragmentation, and cell apoptosis. In parallel, treatment with SNP induced miR-1 expression in a time-dependent manner. Application of miR-1 antisense inhibitors to osteoblasts caused significant inhibition of SNP-induced miR-1 expression. Knocking down miR-1 concurrently attenuated SNP-induced alterations in cell morphology and survival. Consecutively, SNP time-dependently inhibited heat-shock protein (HSP)-70 messenger (m)RNA and protein expressions. A bioinformatic search predicted the existence of miR-1-specific binding elements in the 3’-untranslational region of HSP-70 mRNA. Downregulation of miR-1 expression simultaneously lessened SNP-induced inhibition of HSP-70 mRNA and protein expressions. Consequently, SNP-induced modifications in the mitochondrial membrane potential, caspase-3 activation, DNA fragmentation, and apoptotic insults were significantly alleviated by miR-1 antisense inhibitors. Therefore, this study showed that miR-1 participates in NO-induced apoptotic insults through targeting HSP-70 gene expression.
| Original language | English |
|---|---|
| Pages (from-to) | 246-255 |
| Number of pages | 10 |
| Journal | International Journal of Biological Sciences |
| Volume | 11 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Jan 15 2015 |
Fingerprint
Keywords
- Apoptosis
- HSP-70
- MicroRNA-1
- Mitochondria
- Nitric oxide
ASJC Scopus subject areas
- Cell Biology
- Developmental Biology
- Molecular Biology
- Ecology, Evolution, Behavior and Systematics
- Applied Microbiology and Biotechnology
Cite this
MicroRNA-1 participates in nitric oxide-induced apoptotic insults to MC3T3-E1 cells by targeting heat-shock protein-70. / Lee, Yong Eng; Ye, Hong-Chung; Lin, Yi Ling; Chen, Ruei Ming.
In: International Journal of Biological Sciences, Vol. 11, No. 3, 15.01.2015, p. 246-255.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - MicroRNA-1 participates in nitric oxide-induced apoptotic insults to MC3T3-E1 cells by targeting heat-shock protein-70
AU - Lee, Yong Eng
AU - Ye, Hong-Chung
AU - Lin, Yi Ling
AU - Chen, Ruei Ming
PY - 2015/1/15
Y1 - 2015/1/15
N2 - Our previous studies showed that nitric oxide (NO) could induce osteoblast apoptosis. MicroRNA-1 (miR-1), a skeletal-and cardiac muscle-specific small non-coding RNA, contributes to the regulation of multiple cell activities. In this study, we evaluated the roles of miR-1 in NO-induced insults to osteoblasts and the possible mechanisms. Exposure of mouse MC3T3-E1 cells to sodium nitroprusside (SNP) increased amounts of cellular NO and intracellular reactive oxygen species. Sequentially, SNP decreased cell survival but induced caspase-3 activation, DNA fragmentation, and cell apoptosis. In parallel, treatment with SNP induced miR-1 expression in a time-dependent manner. Application of miR-1 antisense inhibitors to osteoblasts caused significant inhibition of SNP-induced miR-1 expression. Knocking down miR-1 concurrently attenuated SNP-induced alterations in cell morphology and survival. Consecutively, SNP time-dependently inhibited heat-shock protein (HSP)-70 messenger (m)RNA and protein expressions. A bioinformatic search predicted the existence of miR-1-specific binding elements in the 3’-untranslational region of HSP-70 mRNA. Downregulation of miR-1 expression simultaneously lessened SNP-induced inhibition of HSP-70 mRNA and protein expressions. Consequently, SNP-induced modifications in the mitochondrial membrane potential, caspase-3 activation, DNA fragmentation, and apoptotic insults were significantly alleviated by miR-1 antisense inhibitors. Therefore, this study showed that miR-1 participates in NO-induced apoptotic insults through targeting HSP-70 gene expression.
AB - Our previous studies showed that nitric oxide (NO) could induce osteoblast apoptosis. MicroRNA-1 (miR-1), a skeletal-and cardiac muscle-specific small non-coding RNA, contributes to the regulation of multiple cell activities. In this study, we evaluated the roles of miR-1 in NO-induced insults to osteoblasts and the possible mechanisms. Exposure of mouse MC3T3-E1 cells to sodium nitroprusside (SNP) increased amounts of cellular NO and intracellular reactive oxygen species. Sequentially, SNP decreased cell survival but induced caspase-3 activation, DNA fragmentation, and cell apoptosis. In parallel, treatment with SNP induced miR-1 expression in a time-dependent manner. Application of miR-1 antisense inhibitors to osteoblasts caused significant inhibition of SNP-induced miR-1 expression. Knocking down miR-1 concurrently attenuated SNP-induced alterations in cell morphology and survival. Consecutively, SNP time-dependently inhibited heat-shock protein (HSP)-70 messenger (m)RNA and protein expressions. A bioinformatic search predicted the existence of miR-1-specific binding elements in the 3’-untranslational region of HSP-70 mRNA. Downregulation of miR-1 expression simultaneously lessened SNP-induced inhibition of HSP-70 mRNA and protein expressions. Consequently, SNP-induced modifications in the mitochondrial membrane potential, caspase-3 activation, DNA fragmentation, and apoptotic insults were significantly alleviated by miR-1 antisense inhibitors. Therefore, this study showed that miR-1 participates in NO-induced apoptotic insults through targeting HSP-70 gene expression.
KW - Apoptosis
KW - HSP-70
KW - MicroRNA-1
KW - Mitochondria
KW - Nitric oxide
UR - http://www.scopus.com/inward/record.url?scp=84922371484&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84922371484&partnerID=8YFLogxK
U2 - 10.7150/ijbs.11138
DO - 10.7150/ijbs.11138
M3 - Article
C2 - 25678843
AN - SCOPUS:84922371484
VL - 11
SP - 246
EP - 255
JO - International Journal of Biological Sciences
JF - International Journal of Biological Sciences
SN - 1449-2288
IS - 3
ER -