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1,4-dihydropyridine derivatives increase mRNA expression of Psma3, Psmb5, and Psmc6 in rats

Kristīne Dišlere
Kristīne Dišlere
, 
Evita Rostoka
Evita Rostoka
, 
Egils Bisenieks
Egils Bisenieks
, 
Gunars Duburs
Gunars Duburs
, 
Natalia Paramonova
Natalia Paramonova
 y 
Nikolajs Sjakste
Nikolajs Sjakste
   | 28 jun 2021
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Article Category: Original article
Publicado en línea: 28 jun 2021
Páginas: 148 - 156
Recibido: 01 abr 2020
Aceptado: 01 jun 2021
DOI: https://doi.org/10.2478/aiht-2021-72-3422
© 2021 Kristīne Dišlere, Evita Rostoka, Egils Bisenieks, Gunars Duburs, Natalia Paramonova, and Nikolajs Sjakste, published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Figure 1

Formulas of 1,4-dihydropyridine derivatives used in the study
Formulas of 1,4-dihydropyridine derivatives used in the study

The effect of AV-153-Na on Psma3, Psmb5, Psmc6 and Psma6 gene expression in the kidney and liver

AV-153-Na (mg/kg) Kidneys fold difference (SEM range) Liver fold difference (SEM range)
Psma3 Control 1.00 (0.97–1.03) 1.00 (0.95–1.05)
0.05 1.28 (1.21–1.35)* 0.94 (0.82–1.08)
0.50 1.28 (1.12–1.46)* 1.23 (1.19–1.26)
Psmb5 Control 1.00 (0.99–1.02) 1.00 (0.94–1.04)
0.05 1.64 (1.51–1.78)*** 0.79 (0.71–0.87)*
0.50 1.68 (1.47–1.91)*** 1.09 (1.08–1.11)
Psmc6 Control 1.00 (0.97–1.03) 1.00 (0.92–1.09)
0.05 1.39 (1.29–1.51)** 1.19 (1.07–1.33)
0.50 1.47 (1.30–1.66)** 1.61 (1.59–1.62)*
Psma6 Control 1.00 (0.92–1.08) 1.00 (0.94–1.06)
0.05 2.00 (1.78–2.25)*** 1.49 (1.32–1.68)**
0.50 2.17 (1.87–2.52)*** 1.91 (1.86–1.95)***

The effect of AV-153-Ca on Psma3, Psmb5, Psmc6 and Psma6 gene expression in the kidney and liver

AV-153-Ca (mg/kg) Kidney fold difference (SEM range) Liver fold difference (SEM range)
Psma3 Control 1.00 (0.97–1.03) 1.00 (0.95–1.05)
0.05 0.89 (0.76–1.03) 0.96 (0.94–0.99)
0.50 1.00 (0.92–1.09) 0.89 (0.81–0.97)
Psmb5 Control 1.00 (0.99–1.02) 1.00 (0.94–1.04)
0.05 0.62 (0.55–0.71)** 1.05 (1.03–1.08)
0.50 0.85 (0.75–0.95) 0.82 (0.71–0.95)
Psmc6 Control 1.00 (0.97–1.03) 1.00 (0.92–1.09)
0.05 0.85 (0.77–0.93) 0.89 (0.86–0.93)
0.50 0.90 (0.84–0.96) 0.96 (0.88–1.05)
Psma6 Control 1.00 (0.92–1.08) 1.00 (0.94–1.06)
0.05 1.03 (0.96–1.11) 0.87 (0.82–0.93)
0.50 0.98 (0.89–1.07) 1.35 (1.22–1.48)*

Kidney and blood real-time PCR cycle threshold (Ct) values

Kidneys Blood
RNSpolII Psma3 Psmb5 Psmc6 RNSpolII Psma3 Psmb5 Psmc6
Control 20,6336 21,2849 20,2966 18,5916 19,3183 24,7317 23,9346 23,4343
19,9632 21,0402 20,1468 18,5301 19,1140 24,9544 23,9330 23,6485
20,5162 20,6843 19,9793 18,4140 19,5568 23,5918 23,6477 22,6171
19,7661 20,8542 20,0899 18,4168 19,5473 25,3724 23,5371 23,2719
20,4493 21,1992 20,3281 18,7329 19,2752 24,2432 23,6730 22,2758
20,0575 20,7519 19,8123 18,2283 18,0247 24,1311 23,7417 21,8996
19,8994 20,8551 20,1670 18,5733 19,6721 24,1230 22,6278 22,9333
19,9792 21,2709 20,5719 18,8297 18,5737 23,8446 23,0603 22,4729
20,3273 21,4559 20,4872 18,9060 18,9473 24,8475 24,5772 23,0626
20,7163 21,1733 20,4132 18,8730 19,7215 24,5549 23,4031 23,6338
20,1879 21,1945 20,4594 18,7461 18,7025 24,7850 24,1693
18,7703 24,3940 24,0506
Metcarbatone 0.05 mg/kg 21,1421 21,1700 20,2690 18,7102 19,1992 24,9793 24,9819 23,4209
20,6063 20,9449 20,0149 18,6103 18,2122 25,0053 24,6967 22,8411
20,9352 21,4263 20,5656 18,9078 19,6951 24,3028 23,8090 22,9598
20,5415 20,9494 20,0938 18,4946 18,7135 24,5634 24,1763 22,6806
Metcarbatone 0.5 mg/kg 20,8324 20,9915 20,1140 18,8390 18,9062 25,2567 23,8337 23,6736
21,1187 21,0831 20,1682 18,7917 19,2715 25,2724 24,5450 23,6550
21,0912 21,1248 20,3896 18,8515 18,5728 24,6956 23,9355 22,8742
20,6640 21,1151 20,0875 18,7441 18,6701 25,2925 24,5882 23,2121
Etcarbatone 0.05 mg/kg 20,6521 21,3114 20,2236 18,6247 18,8542 24,8812 24,1604 22,9606
21,2283 21,3560 20,3069 18,6993 19,1319 24,8758 24,7965 22,9433
21,3387 21,4437 20,1647 18,7293 18,1798 24,6700 24,4486 22,5183
Etcarbatone 0.5 mg/kg 20,6957 21,2241 20,1316 18,4727 19,2888 24,9479 24,4943 23,1595
21,4283 21,6113 20,5876 18,8926 19,2577 24,8016 24,0260 23,0911
21,0995 21,5415 20,3180 18,8051 18,9519 24,5479 24,2079 22,4058
20,9716 21,4134 20,4994 18,8108 19,0836 24,6532 24,6596 22,5140
Styrylcarbatone 0.05 mg/kg 21,4476 21,4452 20,5627 18,6984 19,5796 23,9558 23,0535 22,6217
20,9010 21,0415 20,1628 18,3986 19,0160 24,8889 24,1739 23,2842
21,3434 21,2509 20,2865 18,6662 18,1215 23,5157 23,3238 21,4245
21,6191 22,0462 21,5846 18,9777 19,5722 25,4267 24,9225 23,4448
Styrylcarbatone 0.5 mg/kg 21,5660 21,5113 21,2236 18,9375 19,1745 23,8688 23,2048 22,2596
21,2131 21,5601 20,7720 18,7713 19,5076 24,7026 23,6100 23,0168
21,0897 21,4685 20,4881 18,7617 18,9420 24,6156 23,8653 23,2664
21,4455 21,6779 20,9215 18,9282
Glutapyrone 0.05 mg/kg 22,0678 22,8544 21,6248 19,8827 18,9078 23,7505 22,4539 22,0790
21,0281 22,1696 20,8820 19,3440 19,1537 23,5877 22,7654 22,3149
21,1787 21,9149 20,8096 19,0287 20,1436 25,5499 23,8626 23,8251
21,3287 21,5062 20,4549 18,7512 19,6614 24,1258 23,0498 23,1506
Glutapyrone 0.5 mg/kg 21,0105 21,8076 20,5749 18,8806 19,3639 24,6586 23,1130 22,9958
20,6910 21,6908 20,2656 18,6775 19,6876 25,6195 23,7417 24,0393
21,1142 21,4909 20,2270 18,7062 19,4588 24,3839 23,1421 22,8727
21,3715 21,4707 20,0467 18,8292 19,4118 24,7691 23,3703 23,2199

The effect of metcarbatone on Psma3, Psmb5 and Psmc6 gene expression in the kidney and blood

Metcarbatone (mg/kg) Kidney fold difference (SEM range) Blood fold difference (SEM range)
Psma3 Control 1.00 (0.93–1.07) 1.00 (0.87–1.14)
0.05 1.44 (1.34–1.54)* 0.76 (0.56–1.04)
0.50 1.61 (1.50–1.74)** 0.53 (0.48–0.58)
Psmb5 Control 1.00 (0.93–1.08) 1.00 (0.84–1.18)
0.05 1.51 (1.40–1.63)** 0.55 (0.39–0.77)
0.50 1.69 (1.60–1.79)** 0.58 (0.51–0.67)
Psmc6 Control 1.00 (0.94–1.07) 1.00 (0.90–1.12)
0.05 1.43 (1.34–1.54)* 0.83 (0.68–1.01)
0.50 1.43 (1.34–1.53)* 0.60 (0.55–0.64)*

The effect of glutapyrone on Psma3, Psmb5 and Psmc6 gene expression in the kidney and blood

Glutapyrone (mg/kg) Kidney fold difference (SEM range) Blood fold difference (SEM range)
Psma3 Control 1.00 (0.93–1.07) 1.00 (0.87–1.14)
0.05 1.10 (0.95–1.26) 1.49 (1.27–1.74)
0.50 1.21 (1.05–1.39) 0.99 (0.86–1.14)
Psmb5 Control 1.00 (0.93–1.08) 1.00 (0.84–1.18)
0.05 1.40 (1.26–1.55) 2.04 (1.94–2.14)*
0.50 1.73 (1.49–2.01)** 1.66 (1.56–1.77)
Psmc6 Control 1.00 (0.94–1.07) 1.00 (0.90–1.12)
0.05 1.46 (1.28–1.66)* 1.30 (1.19–1.42)
0.50 1.59 (1.46–1.73)** 0.96 (0.84–1.11)

The effect of styrylcarbatone on Psma3, Psmb5 and Psmc6 gene expression in the kidney and blood

Styrylcarbatone (mg/kg) Kidney fold difference (SEM range) Blood fold difference (SEM range)
Psma3 Control 1.00 (0.93–1.07) 1.00 (0.87–1.14)
0.05 1.65 (1.53–1.79)** 0.99 (0.78–1.26)
0.50 1.53 (1.43–1.64)** 1.13 (0.93–1.37)
Psmb5 Control 1.00 (0.93–1.08) 1.00 (0.84–1.18)
0.05 1.63 (1.39–1.90)** 0.87 (0.64–1.18)
0.50 1.41 (1.36–1.47)* 1.18 (0.97–1.44)
Psmc6 Control 1.00 (0.94–1.07) 1.00 (0.90–1.12)
0.05 2.05 (1.98–2.13)*** 1.09 (0.90–1.32)
0.50 1.83 (1.75–1.91)*** 1.08 (0.84–1.39)

The effect of etcarbatone on Psma3, Psmb5 and Psmc6 gene expression in the kidney and blood

Etcarbatone (mg/kg) Kidney fold difference (SEM range) Blood fold difference (SEM range)
Psma3 Control 1.00 (0.93–1.07) 1.00 (0.87–1.14)
0.05 1.46 (1.29–1.65)* 0.61 (0.52–0.70)
0.50 1.36 (1.29–1.43)* 0.85 (0.84–0.87)
Psmb5 Control 1.00 (0.93–1.08) 1.00 (0.84–1.18)
0.05 1.82 (1.56–2.12)** 0.45 (0.37–0.55)
0.50 1.61 (1.52–1.71)** 0.66 (0.59–0.74)
Psmc6 Control 1.00 (0.94–1.07) 1.00 (0.90–1.12)
0.05 1.72 (1.52–1.95)** 0.79 (0.71–0.88)
0.50 1.62 (1.53–1.72)** 1.07 (0.99–1.17)

Liver real-time PCR cycle threshold (Ct) values

Kidneys Liver
RNSpolII Psma3 Psmb5 Psmc6 Psma6 RNSpolII Psma3 Psmb5 Psmc6 Psma6
Control 20,5970 22,5839 19,2551 19,1623 19,9986 19,8560 23,0557 21,1670 18,6385 19,8489
20,4384 22,5746 19,0794 18,8645 19,5620 19,5794 22,9181 21,1984 18,6208 19,6455
20,4358 22,5837 19,1140 18,8865 19,7310 19,9334 23,3011 21,1796 19,6168 20,4226
20,5461 22,7381 19,0685 19,1585 19,7124 19,7203 23,1264 21,1636 19,4941 20,2836
20,3772 22,3517 19,0689 19,2026 20,2427 19,1888 22,9224 21,0717 19,1761 19,8373
20,3640 22,2591 18,9613 18,9177 19,7695 19,7114 23,1850 21,1812 19,1708 20,0905
20,4210 22,1444 19,0667 18,8171 19,3981 19,8140 23,5071 21,3909 19,3937 20,2497
20,5429 22,3808 19,2618 20,5558 19,7631 23,3798 21,3486 19,0927 20,2443
20,4095 22,3303 18,9823 20,3727 19,6435 23,5475 21,2771 19,3322 20,4155
19,9648 22,0525 18,7116 19,2846
AV-153-Na 0.05 mg/kg 21,1756 22,9314 19,3199 19,5803 20,0066 19,3193 22,6985 21,0440 18,3758 18,9400
22,0513 23,4752 19,6423 19,9317 20,6172 18,8415 22,8245 20,9705 18,3795 19,0355
21,4856 23,2240 19,4647 19,6623 19,8643 19,5196 22,7070 21,0585 18,3857 19,0187
21,6234 23,2381 19,5993 19,5928 19,6469 18,8631 22,7883 20,9608 18,3031 18,9503
AV-153-Na 0.5 mg/kg 21,9367 23,2775 19,4898 19,8077 20,0014 19,6059 22,7776 20,9764 18,4171 19,0567
21,6564 23,2385 19,5634 19,4900 19,8338 19,6035 22,8215 21,0093 18,4078 19,0701
21,2077 23,2004 19,4074 19,5859 19,9741 19,5527 22,8589 20,9877 18,3254 19,1177
AV-153-Ca 0.05 mg/kg 19,7019 22,0370 19,1800 18,7166 19,3175 19,3393 22,9415 20,8086 19,1408 19,8715
19,8564 22,2813 19,3695 18,7706 19,2143 19,6280 23,3113 21,0154 19,1477 20,3142
20,1111 21,8349 19,0583 18,6593 19,3757 19,3697 22,8512 20,9235 18,9642 20,2187
19,6506 23,1935 21,0658 19,3068 20,0824
AV-153-Ca 0.5 mg/kg 20,3086 22,0432 19,5138 18,8374 19,3591 19,4528 22,9892 20,7577 19,0212 19,3202
20,5201 22,7760 18,8733 19,2125 20,2666 19,5880 23,2170 21,2606 19,0527 19,6300
19,5801 21,8729 18,8382 18,7051 19,3437 18,8662 23,0295 21,3512 18,8270 19,3601
20,1326 22,0602 18,9902 18,8147 19,6876 19,5368 23,2560 21,5740 19,0952 19,4394
20,1226 21,8402 18,8235 18,8101 19,4492 19,5666 23,0126 21,1141 18,7163 19,2355
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