Protective role of cyclosporine A and minocycline on mitochondrial disequilibrium-related podocyte injury and proteinuria occurrence induced by adriamycin

被引：51

作者：

Guan, Na ^{[1
]}

Ren, Ya-Li ^{[2
]}

Liu, Xiao-Ya ^{[1
]}

Zhang, Ying ^{[3
]}

Pei, Pei ^{[3
]}

Zhu, Sai-Nan ^{[4
]}

Fan, Qingfeng ^{[1
]}

机构：

[1] Peking Univ, Hosp 1, Dept Pediat, Beijing 100034, Peoples R China

[2] Peking Univ, Hosp 1, Dept Electron Microscopy, Beijing 100034, Peoples R China

[3] Peking Univ, Hosp 1, Dept Cent Lab, Beijing 100034, Peoples R China

[4] Peking Univ, Hosp 1, Dept Biostat, Beijing 100034, Peoples R China

来源：

NEPHROLOGY DIALYSIS TRANSPLANTATION | 2015年 / 30卷 / 06期

基金：

中国国家自然科学基金;

关键词：

cyclosporine A; minocycline; mitochondria; mitofusin; podocyte; FOCAL SEGMENTAL GLOMERULOSCLEROSIS; ACUTE KIDNEY INJURY; SKELETAL-MUSCLE; CELL APOPTOSIS; RODENT MODELS; NEPHROPATHY; DYNAMICS; ACTIVATION; MORPHOLOGY; DISEASES;

D O I：

10.1093/ndt/gfv015

中图分类号：

R3 [基础医学]; R4 [临床医学];

学科分类号：

100103 [病原生物学]; 100218 [急诊医学];

摘要：

Background. Dysfunction of mitochondria is involved in podocyte injury in some kidney diseases, but the relationship between abnormal mitochondrial morphology and podocyte injury as well as the underlying mechanism is still unclear. This study aims to investigate dynamic changes of mitochondrial morphology and the potential molecular events in an adriamycin (ADR)-induced podocyte injury model. Methods. Podocyte apoptosis was evaluated by annexin V assay. Podocyte mitochondrial membrane potential (MMP) was measured with MitoCapture kit. Double staining was used to show the distribution changes of mitochondria and actin filament as well as mitofusin proteins and podocin. Mitochondrial shape descriptors were obtained using analySIS Image system. Effects of cyclosporine A (CsA) or minocycline (Mcy) on mitochondrial morphology were explored in ADR-induced nephropathy rats. Results. ADR caused podocyte damage displaying as induction of cellular apoptosis and increase of activated caspase 3 and cytochrome c. The MMP level was decreased remarkably in ADR-treated podocytes. Mitochondrial morphological changes induced by ADR occurred rapidly from large and ellipsoid shape to the small, long and irregular. ADR significantly decreased surface area, perimeter and circularity, while increasing aspect ratio of mitochondria. In addition, mitochondria number transiently increased at 6 h following ADR application. Mitochondria intensity was increased along with punctate mitochondria formation, which co-localized with polymerized actin cytoskeleton in ADR podocytes. In ADR-induced nephropathy rats, 24-h proteinuria was decreased significantly by CsA or Mcy. ADR-induced abnormal changes of mitochondrial morphology were restored by CsA or Mcy. The induction of mitofusin proteins and the reduction of podocin in ADR rat glomeruli were rescued by CsA or Mcy. Conclusions. Mitochondrial dysfunction may be an early event in ADR-induced podocyte damage, and the protective role of CsA or Mcy may be mediated partially by improving mitochondrial function through inhibiting the induction of mitofusin proteins.

引用

页码：957 / 969

页数：14

共 41 条

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