Table 1.
Tacrolimus (µmol·L−1) | Cyclosporin (µmol·L−1) | ||||||
---|---|---|---|---|---|---|---|
Control | 0.05 | 0.10 | 0.20 | 2.5 | 5.0 | 10 | |
(A)Six hours incubation at basal (6.6 mmol·L−1) glucose concentration | |||||||
Calcineurin | 0.85 (0.84–0.85) | 0.76 (0.75–0.83) | 0.93 (0.89–0.97) | 0.78 (0.77–0.79) | 0.8 (0.8–0.8) | 0.83 (0.73–0.93) | 0.74 (0.71–0.77) |
Bax/Bcl-2 | 0.71 (0.51–0.75) | 0.74 (0.69–0.79) | 0.77 (0.75–0.78) | 0.82 (0.81–0.82) | 0.72 (0.66–0.78) | 0.76 (0.7–0.83) | 0.92 (0.86–0.99) |
NFATc1 | 1.03 (0.96–1.13) | 0.99 (0.89–1.09) | 1.06 (0.94–1.18) | 1.02 (0.95–1.09) | 1.17 (1.12–1.22) | 1.11 (1.07–1.14) | 1.09 (1.04–1.13) |
NFATc2 | 12.76 (4.29–13.7) | 7.77 (5.65–9.9) | 6.88 (5.11–8.64) | 3.77 (3.64–3.89) | 2.38 (2–2.76) | 5.12 (0.93–9.32) | 5.07 (2.15–7.98) |
NFATc3 | 1.11 (1.04–1.34) | 0.91 (0.88–0.94) | 1.09 (0.96–1.22) | 1.23 (1.17–1.28) | 1.14 (1.11–1.17) | 1.11 (1.04–1.19) | 1.29 (1.05–1.54) |
NFATc4 | 0.35 (0.28–0.36) | 0.37 (0.35–0.39) | 0.39 (0.32–0.45) | 0.36 (0.31–0.41) | 0.38 (0.32–0.44) | 0.41 (0.36–0.46) | 0.37 (0.36–0.38) |
(B)Six hours incubation at stimulatory (16.7 mmol·L−1) glucose concentration | |||||||
Calcineurin | 0.83 (0.76–0.96) | 0.89 (0.76–0.96) | 0.8 (0.78–0.83) | 0.94 (0.84–1.04) | 0.86 (0.83–0.9) | 0.82 (0.74–0.9) | 0.72 (0.69–0.75) |
Bax/Bcl-2 | 0.9 (0.83–1.05) | 0.89 (0.84–0.93) | 0.78 (0.66–0.92) | 0.98 (0.74–1.21) | 0.98 (0.96–0.99) | 1.15 (1.1–1.2) | 1.34 (1.22–1.46) |
NFATc1 | 0.75 (0.71–0.77) | 0.83 (0.73–0.93) | 0.83 (0.78–0.87) | 0.8 (0.64–0.97) | 0.75 (0.72–0.77) | 0.82 (0.76–0.88) | 0.75 (0.71–0.78) |
NFATc2 | 4.12 (0.97–9.72) | 24.16 (2.6–45.7) | 4.53 (3.17–5.9) | 4.19 (2.87–5.51) | 1.56 (0.95–2.17) | 4.42 (1.31–7.52) | 26.27 (8.34–44) |
NFATc3 | 1.11 (0.98–1.47) | 1.06 (1.02–1.09) | 1.06 (0.9–1.23) | 1.13 (1.12–1.14) | 1.14 (1.13–1.15) | 1.16 (1.09–1.22) | 1.34 (1.32–1.36) |
NFATc4 | 0.21 (0.18–0.22) | 0.19 (0.18–0.19) | 0.19 (0.18–0.21) | 0.19 (0.19–0.19) | 0.19 (0.18–0.19) | 0.18 (0.17–0.18) | 0.20 (0.19–0.21) |
(C)Twenty-four hours of incubation at basal (6.6 mmol·L−1) glucose concentration | |||||||
Calcineurin | 0.93 (0.83–1.08) | 1.01 (0.98–1.05) | 0.91 (0.9–0.93) | 1.00 (0.95–1.05) | 1.22 (1.0–1.44) | 0.95 (0.93–0.96) | 1.06 (0.93–1.2) |
Bax/Bcl-2 | 0.74 (0.66–0.89) | 0.66 (0.65–0.68) | 0.79 (0.75–0.82) | 0.67 (0.61–0.73) | 0.74 (0.68–0.79) | 0.59 (0.56–0.62) | 0.71 (0.65–0.76) |
NFATc1 | 0.88 (0.78–0.95) | 0.7 (0.69–0.71) | 0.77 (0.73–0.8) | 0.8 (0.73–0.86) | 1.25 (1.23–1.26) | 1.11 (1.07–1.15) | 1.08 (1.04–1.12) |
NFATc2 | 17.75 (4.76–60.9) | 19.26 (16.8–21.7) | 18.13 (15.7–20.6) | 12.93 (4.58–21.3) | 42.11 (15.3–68.9) | 5.18 (5.03–5.34) | 17.13 (15.3–19) |
NFATc3 | 1.47 (1.29–1.75) | 1.57 (1.48–1.67) | 1.82 (1.73–1.91) | 2.1 (1.91–2.28) | 1.59 (1.34–1.84) | 1.5 (1.38–1.62) | 1.52 (1.44–1.61) |
NFATc4 | 0.81 (0.62–0.88) | 0.9 (0.85–0.96) | 0.94 (0.86–1.02) | 0.99 (0.95–1.04) | 1.15 (1.05–1.24) | 1.1 (1.02–1.18) | 1.12 (1.05–1.19) |
(D)Twenty-four hours of incubation at stimulatory (16.7 mmol·L−1) glucose concentrations | |||||||
Calcineurin | 1.0 (0.92–1.29) | 0.94 (0.83–1.15) | 0.95 (0.89–1.28) | 0.93 (0.91–0.99) | 1.03 (0.93–1.14) | 0.84 (0.76–0.92) | 0.74 (0.62–0.85) |
Bax/Bcl-2 | 1.08 (0.83–1.53) | 0.98 (0.85–1.23) | 0.99 (0.89–1.41) | 1.14 (1.02–1.37) | 1.12 (1.03–1.22) | 1.18 (1.15–1.22) | 1.42 (1.14–1.71) |
NFATc1 | 0.64 (0.53–0.71) | 0.6 (0.51–0.78) | 0.61 (0.5–0.75) | 0.61 (0.56–0.68) | 0.65 (0.6–0.7) | 0.64 (0.6–0.68) | 0.59 (0.58–0.6) |
NFATc2 | 20.05 (16.5–44.2) | 23.04 (12.5–29.9) | 46.97 (12.9–498) | 53.23 (11.2–124) | 16.31 (9.61–23) | 8.22 (3.06–13.4) | 36.0 (12.9–59.1) |
NFATc3 | 1.66 (1.33–1.79) | 1.53 (1.31–1.79) | 1.62 (1.27–1.89) | 1.54 (1.36–1.8) | 1.75 (1.68–1.82) | 1.44 (1.38–1.49) | 1.48 (1.29–1.68) |
NFATc4 | 0.26 (0.25–0.36) | 0.29 (0.23–0.33) | 0.34 (0.33–0.65) | 0.45 (0.31–0.65) | 0.29 (0.22–0.36) | 0.28 (0.26–0.29) | 0.28 (0.22–0.35) |
Data are medians with range. n= 3 for controls and n= 2 for each drug concentration.
Bax, Bcl-2 associated X protein; Bcl-2, B-cell leukaemia/lymphoma 2; HSP, heat shock protein; NFATc, nuclear factor of activated T cells cytoplasmic.