Reference - Detail
| RRC ID | 38551 |
|---|---|
| Author | Yang D, Yaguchi T, Nakano T, Nishizaki T. |
| Title | Adenosine activates AMPK to phosphorylate Bcl-XL responsible for mitochondrial damage and DIABLO release in HuH-7 cells. |
| Journal | Cell Physiol Biochem |
| Abstract |
BACKGROUND/AIMS:Accumulating evidence has pointed to AMP-activated protein kinase (AMPK) as an inducer of apoptosis in a variety of cancer cells. The present study aimed at understanding AMPK signals for adenosine-induced HuH-7 cell apoptosis. METHODS:Cell viability, AMPK activity, mitochondrial membrane potentials, phosphorylation of Bcl-X(L), in situ DIABLO mobilizations, and caspase-3 activity were monitored in HuH-7 cells. Plasmid DNAs for DIABLO-GFP, mutant Bcl-X(L), dominant negative mutant AMPKα2 and the siRNAs to silence the AMPKα1 or AMPKα2 targeted gene were constructed and transfected. RESULTS:Adenosine or the AMPK activator AICAR induced apoptosis in HuH-7 cells, and no synergistic effect was obtained with co-treatment. Adenosine activated AMPK, to phosphorylate Bcl-X(L). Adenosine or AICAR disrupted mitochondrial membrane potentials, and the effect was inhibited by knocking-down AMPKα1 and/or AMPKα2, expressing dominant negative mutant AMPKα2 or mutant Bcl-X(L) lacking Ser/Thr phosphorylation sites. AICAR stimulated DIABLO release from the mitochondria, and the release was suppressed by expressing the mutant Bcl-X(L). AICAR activated caspase-3, which was also inhibited by expressing the mutant Bcl-X(L). CONCLUSION:Adenosine activates AMPK, to disrupt mitochondrial membrane potentials through Bcl-X(L) phosphorylation, allowing DIABLO release from the mitochondria, as a factor for caspase-3 activation to induce HuH-7 cell apoptosis. |
| Volume | 27(1) |
| Pages | 71-8 |
| Published | 2011-1-1 |
| DOI | 10.1159/000325207 |
| PII | 000325207 |
| PMID | 21325824 |
| MeSH | AMP-Activated Protein Kinases / genetics AMP-Activated Protein Kinases / metabolism* Adenosine / pharmacology* Aminoimidazole Carboxamide / analogs & derivatives Aminoimidazole Carboxamide / pharmacology Apoptosis Apoptosis Regulatory Proteins Cell Line, Tumor Humans Intracellular Signaling Peptides and Proteins / metabolism* Membrane Potential, Mitochondrial / drug effects Mitochondria / drug effects* Mitochondrial Proteins / metabolism* Phosphorylation RNA Interference RNA, Small Interfering Ribonucleotides / pharmacology bcl-X Protein / metabolism* |
| IF | 5.5 |
| Times Cited | 19 |
| WOS Category | PHYSIOLOGY CELL BIOLOGY |
| Resource | |
| Human and Animal Cells | HuH-7(RCB1366) |