Effects of microfilament and microtubule inhibitors on Iron metabolism and Tf cycle in reticulocytes
. | . | . | . | Incorporation of 59Fe into* . | . | . | . | |
|---|---|---|---|---|---|---|---|---|
| Reagent . | Concentration, μM . | Tf internalization, % (max. time)† . | Tf release, % (max. time)† . | Cells, %‡ . | Heme, %‡ . | Endosomal 59Fe incorporated into heme, %‡ . | Mitochondrial 59Fe incorporated into heme, %‡ . | |
| WT | ||||||||
| 0.1 | 97.1 (30) | 90.7 (6) | 92.9 | 90.5 | 89.6 (8) | 97.5 | ||
| 1.0 | 94.3 (30) | 90.6 (6) | 72.3 | 65.5 | 76.4 (8) | 95.4 | ||
| 10.0 | 76.6 (30) | 90.6 (6) | 53.9 | 40.2 | 73.0 (8) | 95.4 | ||
| 50.0 | 60.5 (30) | 87.7 (6) | ND | ND | 61.8 (8) | ND | ||
| ML-9 | ||||||||
| 50.0 | 56.9 (3) | 59.4 (2) | 67.2 | 65.7 | 74.3 (4) | ND | ||
| 100.0 | 40.6 (3) | 48.6 (2) | 61.1 | 52.2 | 66.6 (4) | ND | ||
| 200.0 | 32.5 (3) | 35.2 (2) | 30.5 | 13.2 | 61.5 (4) | ND | ||
| W-7 | ||||||||
| 10.0 | ND | ND | 96.8 | 95.6 | ND | |||
| 50.0 | 83.4 (2) | 46.8 (2) | 78.3 | 74.2 | 77.9 (4) | ND | ||
| 100.0 | 69.2 (2) | 33.6 (2) | 55.5 | 48.6 | 53.0 (4) | 96.5 | ||
| 200.0 | 37.4 (2) | 12.8 (2) | 32.5 | 22.6 | 30.4 (4) | 94.5 | ||
| BDM | ||||||||
| 10 000.0 | 88.4 (4) | 95.9 (2) | 85.5 | 87.0 | 54.6 (4) | 88.3 | ||
| 20 000.0 | 72.6 (4) | 95.5 (2) | 65.2 | 61.1 | 44.9 (4) | 84.8 | ||
| Nocodazole | ||||||||
| 10.0 | 112.7 (10) | ND | 114.2 | 118.4 | 114.2 (8) | ND | ||
| 50.0 | 114.7 (10) | ND | 122.7 | 128.5 | 112.8 (8) | ND | ||
| 100.0 | 118.9 (30) | ND | 117.7 | 122.0 | 112.7 (8) | ND | ||
. | . | . | . | Incorporation of 59Fe into* . | . | . | . | |
|---|---|---|---|---|---|---|---|---|
| Reagent . | Concentration, μM . | Tf internalization, % (max. time)† . | Tf release, % (max. time)† . | Cells, %‡ . | Heme, %‡ . | Endosomal 59Fe incorporated into heme, %‡ . | Mitochondrial 59Fe incorporated into heme, %‡ . | |
| WT | ||||||||
| 0.1 | 97.1 (30) | 90.7 (6) | 92.9 | 90.5 | 89.6 (8) | 97.5 | ||
| 1.0 | 94.3 (30) | 90.6 (6) | 72.3 | 65.5 | 76.4 (8) | 95.4 | ||
| 10.0 | 76.6 (30) | 90.6 (6) | 53.9 | 40.2 | 73.0 (8) | 95.4 | ||
| 50.0 | 60.5 (30) | 87.7 (6) | ND | ND | 61.8 (8) | ND | ||
| ML-9 | ||||||||
| 50.0 | 56.9 (3) | 59.4 (2) | 67.2 | 65.7 | 74.3 (4) | ND | ||
| 100.0 | 40.6 (3) | 48.6 (2) | 61.1 | 52.2 | 66.6 (4) | ND | ||
| 200.0 | 32.5 (3) | 35.2 (2) | 30.5 | 13.2 | 61.5 (4) | ND | ||
| W-7 | ||||||||
| 10.0 | ND | ND | 96.8 | 95.6 | ND | |||
| 50.0 | 83.4 (2) | 46.8 (2) | 78.3 | 74.2 | 77.9 (4) | ND | ||
| 100.0 | 69.2 (2) | 33.6 (2) | 55.5 | 48.6 | 53.0 (4) | 96.5 | ||
| 200.0 | 37.4 (2) | 12.8 (2) | 32.5 | 22.6 | 30.4 (4) | 94.5 | ||
| BDM | ||||||||
| 10 000.0 | 88.4 (4) | 95.9 (2) | 85.5 | 87.0 | 54.6 (4) | 88.3 | ||
| 20 000.0 | 72.6 (4) | 95.5 (2) | 65.2 | 61.1 | 44.9 (4) | 84.8 | ||
| Nocodazole | ||||||||
| 10.0 | 112.7 (10) | ND | 114.2 | 118.4 | 114.2 (8) | ND | ||
| 50.0 | 114.7 (10) | ND | 122.7 | 128.5 | 112.8 (8) | ND | ||
| 100.0 | 118.9 (30) | ND | 117.7 | 122.0 | 112.7 (8) | ND | ||
ND indicates not determined.
Reticulocytes (20% suspension) were incubated with 59Fe-Tf (10 μM, in terms of transferrin concentration) for 60 minutes, following which radioactivity in washed cells and extracted heme was evaluated.
Maximum effects at time intervals indicated in parentheses (minutes).
Results are expressed as percentages of corresponding controls.