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Tanshinone IIA attenuates renal injury during hypothermic preservation via the MEK/ERK1/2/GSK-3β pathway

BACKGROUND: Oxidative stress-induced injury during hypothermic preservation is a universal problem that delays graft function and decrease the success of organ transplantation. Tanshinone IIA (Tan IIA) was reported to exhibit a variety of biochemical activities, including protection against oxidativ...

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Autores principales: Xu, Linhao, Xu, Yizhou, Zhu, Zhoujing, Gu, Huiquan, Chen, Chaofeng, Chen, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501657/
https://www.ncbi.nlm.nih.gov/pubmed/34625061
http://dx.doi.org/10.1186/s12906-021-03427-7
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author Xu, Linhao
Xu, Yizhou
Zhu, Zhoujing
Gu, Huiquan
Chen, Chaofeng
Chen, Jian
author_facet Xu, Linhao
Xu, Yizhou
Zhu, Zhoujing
Gu, Huiquan
Chen, Chaofeng
Chen, Jian
author_sort Xu, Linhao
collection PubMed
description BACKGROUND: Oxidative stress-induced injury during hypothermic preservation is a universal problem that delays graft function and decrease the success of organ transplantation. Tanshinone IIA (Tan IIA) was reported to exhibit a variety of biochemical activities, including protection against oxidative stress. Therefore, the specific molecular pathway by which Tan IIA protects renal tissues during preservation was investigated in this study. METHODS: In vivo study, Sprague-Dawley (SD) rats were divided into twelve groups and the kidneys were isolated and preserved in different solutions for 0, 24 or 48 h, respectively: control group (Celsior solution) and Tan II groups (Celsior solution containing 10, 50,100 μM). In vitro study, primary renal cell from SD rats was cultured which was treated H(2)O(2) (800 μM) for 6 h to mimic oxidative stress injury. Four groups were finally divided: control group; H(2)O(2) group; H(2)O(2) + Tan IIA group; H(2)O(2) + Tan IIA + G15 group. RESULTS: In present study, we demonstrate data indicating that a significant increase in the superoxide dismutase (SOD) activity and a decrease in the reactive oxygen species (ROS) content were observed in the kidneys and renal cells preserved with Tan IIA compared with those preserved with the Celsior solution alone after 24 h and 48 h of hypothermic preservation (P < 0.01). The expression of phosphorylated mitogen-activated protein kinase kinase (MEK), phosphorylated extracellular signal-regulated protein kinases 1/2 (ERK1/2), phosphorylated glycogen synthase kinase-3β (GSK-3β) and cleaved caspase-3 was lower in the kidneys and renal cells preserved with Tan IIA than in those preserved with the Celsior solution alone after 24 h and 48 h of hypothermic preservation (P < 0.01). The mitochondrial morphology was rescued and adenosine triphophate (ATP) production and mitochondrial membrane potential were increased in the Tan IIA groups. Finally, Tan IIA also decreased cell apoptosis. CONCLUSION: It suggests that the supplementation of the standard Celsior solution with Tan IIA may significantly improve long-term kidney preservation. Tan IIA attenuated oxidative stress injury and decreased apoptosis levels via activation of the MEK/ERK1/2/GSK-3β signaling pathway during kidney hypothermic preservation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12906-021-03427-7.
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spelling pubmed-85016572021-10-20 Tanshinone IIA attenuates renal injury during hypothermic preservation via the MEK/ERK1/2/GSK-3β pathway Xu, Linhao Xu, Yizhou Zhu, Zhoujing Gu, Huiquan Chen, Chaofeng Chen, Jian BMC Complement Med Ther Research BACKGROUND: Oxidative stress-induced injury during hypothermic preservation is a universal problem that delays graft function and decrease the success of organ transplantation. Tanshinone IIA (Tan IIA) was reported to exhibit a variety of biochemical activities, including protection against oxidative stress. Therefore, the specific molecular pathway by which Tan IIA protects renal tissues during preservation was investigated in this study. METHODS: In vivo study, Sprague-Dawley (SD) rats were divided into twelve groups and the kidneys were isolated and preserved in different solutions for 0, 24 or 48 h, respectively: control group (Celsior solution) and Tan II groups (Celsior solution containing 10, 50,100 μM). In vitro study, primary renal cell from SD rats was cultured which was treated H(2)O(2) (800 μM) for 6 h to mimic oxidative stress injury. Four groups were finally divided: control group; H(2)O(2) group; H(2)O(2) + Tan IIA group; H(2)O(2) + Tan IIA + G15 group. RESULTS: In present study, we demonstrate data indicating that a significant increase in the superoxide dismutase (SOD) activity and a decrease in the reactive oxygen species (ROS) content were observed in the kidneys and renal cells preserved with Tan IIA compared with those preserved with the Celsior solution alone after 24 h and 48 h of hypothermic preservation (P < 0.01). The expression of phosphorylated mitogen-activated protein kinase kinase (MEK), phosphorylated extracellular signal-regulated protein kinases 1/2 (ERK1/2), phosphorylated glycogen synthase kinase-3β (GSK-3β) and cleaved caspase-3 was lower in the kidneys and renal cells preserved with Tan IIA than in those preserved with the Celsior solution alone after 24 h and 48 h of hypothermic preservation (P < 0.01). The mitochondrial morphology was rescued and adenosine triphophate (ATP) production and mitochondrial membrane potential were increased in the Tan IIA groups. Finally, Tan IIA also decreased cell apoptosis. CONCLUSION: It suggests that the supplementation of the standard Celsior solution with Tan IIA may significantly improve long-term kidney preservation. Tan IIA attenuated oxidative stress injury and decreased apoptosis levels via activation of the MEK/ERK1/2/GSK-3β signaling pathway during kidney hypothermic preservation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12906-021-03427-7. BioMed Central 2021-10-08 /pmc/articles/PMC8501657/ /pubmed/34625061 http://dx.doi.org/10.1186/s12906-021-03427-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Xu, Linhao
Xu, Yizhou
Zhu, Zhoujing
Gu, Huiquan
Chen, Chaofeng
Chen, Jian
Tanshinone IIA attenuates renal injury during hypothermic preservation via the MEK/ERK1/2/GSK-3β pathway
title Tanshinone IIA attenuates renal injury during hypothermic preservation via the MEK/ERK1/2/GSK-3β pathway
title_full Tanshinone IIA attenuates renal injury during hypothermic preservation via the MEK/ERK1/2/GSK-3β pathway
title_fullStr Tanshinone IIA attenuates renal injury during hypothermic preservation via the MEK/ERK1/2/GSK-3β pathway
title_full_unstemmed Tanshinone IIA attenuates renal injury during hypothermic preservation via the MEK/ERK1/2/GSK-3β pathway
title_short Tanshinone IIA attenuates renal injury during hypothermic preservation via the MEK/ERK1/2/GSK-3β pathway
title_sort tanshinone iia attenuates renal injury during hypothermic preservation via the mek/erk1/2/gsk-3β pathway
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501657/
https://www.ncbi.nlm.nih.gov/pubmed/34625061
http://dx.doi.org/10.1186/s12906-021-03427-7
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