| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-139 |
Sentence |
denotes |
Molecular interaction and functional regulation of ClC-3 by Ca2+/calmodulin-dependent protein kinase II (CaMKII) in human malignant glioma. |
| T2 |
140-225 |
Sentence |
denotes |
Glioblastoma multiforme is the most common and lethal primary brain cancer in adults. |
| T3 |
226-327 |
Sentence |
denotes |
Tumor cells diffusely infiltrate the brain making focal surgical and radiation treatment challenging. |
| T4 |
328-463 |
Sentence |
denotes |
The invasion of glioma cells into normal brain is facilitated by the activity of ion channels aiding dynamic regulation of cell volume. |
| T5 |
464-565 |
Sentence |
denotes |
Recent studies have specifically implicated ClC-3, a voltage-gated chloride channel, in this process. |
| T6 |
566-653 |
Sentence |
denotes |
However, the interaction between ClC-3 activity and cell movement is poorly understood. |
| T7 |
654-866 |
Sentence |
denotes |
Here, we demonstrate that ClC-3 is highly expressed on the plasma membrane of human glioma cells where its activity is regulated through phosphorylation via Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). |
| T8 |
867-1074 |
Sentence |
denotes |
Intracellular infusion of autoactivated CaMKII via patch pipette enhanced chloride currents 3-fold, and this regulation was inhibited by autocamtide-2 related inhibitory peptide, a CaMKII-specific inhibitor. |
| T9 |
1075-1240 |
Sentence |
denotes |
CaMKII modulation of chloride currents was also lost upon stable small hairpin RNA knockdown of ClC-3 channels indicating a specific interaction of ClC-3 and CaMKII. |
| T10 |
1241-1362 |
Sentence |
denotes |
In ClC-3-expressing cells, inhibition of CaMKII reduced glioma invasion to the same extent as direct inhibition of ClC-3. |
| T11 |
1363-1525 |
Sentence |
denotes |
The importance of the molecular interaction of ClC-3 and CaMKII is further supported by our finding that CaMKII co-localizes and co-immunoprecipitates with ClC-3. |
| T12 |
1526-1639 |
Sentence |
denotes |
ClC-3 and CaMKII also co-immunoprecipitate in tissue biopsies from patients diagnosed with grade IV glioblastoma. |
| T13 |
1640-1729 |
Sentence |
denotes |
These tumor samples show 10-fold higher ClC-3 protein expression than nonmalignant brain. |
| T14 |
1730-1941 |
Sentence |
denotes |
These data suggest that CaMKII is a molecular link translating intracellular calcium changes, which are intrinsically associated with glioma migration, to changes in ClC-3 conductance required for cell movement. |