scholarly journals Aristolochic acid induces renal fibrosis by arresting proximal tubular cells in G2/M phase mediated by HIF‐1α

2020 ◽  
Vol 34 (9) ◽  
pp. 12599-12614
Author(s):  
Hao Zhao ◽  
Na Jiang ◽  
Yachun Han ◽  
Ming Yang ◽  
Peng Gao ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Aristolochic Acid ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
M Phase ◽  
Proximal Tubular

scholarly journals DsbA-L mediated renal tubulointerstitial fibrosis in UUO mice

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaozhou Li ◽  
Jian Pan ◽  
Huiling Li ◽  
Guangdi Li ◽  
Xiangfeng Liu ◽  
...  
Keyword(s):  
Low Dose ◽  
Aristolochic Acid ◽  
Tissue Growth ◽  
Tubulointerstitial Fibrosis ◽  
Obstructive Nephropathy ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Renal Tubulointerstitial Fibrosis ◽  
Proximal Tubular ◽  
Apoptosis And Inflammation

Abstract Recent studies have reported that upregulation of disulfide-bond A oxidoreductase-like protein (DsbA-L) prevented lipid-induced renal injury in diabetic nephropathy (DN). However, the role and regulation of proximal tubular DsbA-L for renal tubulointerstitial fibrosis (TIF) remains unclear. In current study, we found that a proximal tubules-specific DsbA-L knockout mouse (PT-DsbA-L-KO) attenuated UUO-induced TIF, renal cell apoptosis and inflammation. Mechanistically, the DsbA-L interacted with Hsp90 in mitochondria of BUMPT cells which activated the signaling of Smad3 and p53 to produce connective tissue growth factor (CTGF) and then resulted in accumulation of ECM of BUMPT cells and mouse kidney fibroblasts. In addition, the progression of TIF caused by UUO, ischemic/reperfusion (I/R), aristolochic acid, and repeated acute low-dose cisplatin was also alleviated in PT-DsbA-L-KO mice via the activation of Hsp90 /Smad3 and p53/CTGF axis. Finally, the above molecular changes were verified in the kidney biopsies from patients with obstructive nephropathy (Ob). Together, these results suggest that DsbA-L in proximal tubular cells promotes TIF via activation of the Hsp90 /Smad3 and p53/CTGF axis.

scholarly journals Two New Aristolochic Acid Analogues from the Roots of Aristolochia contorta with Significant Cytotoxic Activity

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 44
Author(s):  
Hong-Jian Ji ◽  
Jia-Yuan Li ◽  
Shi-Fei Wu ◽  
Wen-Yong Wu ◽  
Chang-Liang Yao ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Aristolochic Acid ◽  
Spectroscopic Methods ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Mtt Method ◽  
Structure Activity ◽  
Proximal Tubular ◽  
Aristolochia Contorta ◽  
First Time

Twelve compounds, including two new aristolochic acid analogues with a formyloxy moiety (9–10) and 10 known aristolochic acid derivates (1–8 and 11–12), were obtained from the roots of Aristolochiacontorta. Their structures were elucidated using extensive spectroscopic methods. Their cytotoxic activity in human proximal tubular cells HK-2 was evaluated by the MTT method, which has been widely used to assess cell viability. Among these molecules, compounds 3 and 9 were found to be more cytotoxic. Furthermore, molecular modeling was used to evaluate, for the first time, the interactions of compounds 3 and 9 with the target protein organic anionic transporter 1 (OAT1) that plays a key role in mediating aristolochic acid nephropathy. Structure–activity relationships are briefly discussed.

Low-affinity transport of pyroglutamyl-histidine in renal brush-border membrane vesicles

1989 ◽  
Vol 257 (5) ◽  
pp. C971-C975 ◽  
Author(s):  
H. A. Skopicki ◽  
K. Fisher ◽  
D. Zikos ◽  
G. Flouret ◽  
D. R. Peterson
Keyword(s):  
Brush Border ◽  
Brush Border Membrane ◽  
Membrane Vesicles ◽  
Brush Border Membrane Vesicles ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Luminal Membrane ◽  
Renal Brush Border Membrane ◽  
Proximal Tubular ◽  
Renal Brush Border

These studies were performed to determine if a low-affinity carrier is present in the luminal membrane of proximal tubular cells for the transport of the dipeptide, pyroglutamyl-histidine (pGlu-His). We have previously described the existence of a specific, high-affinity, low-capacity [transport constant (Kt) = 9.3 X 10(-8) M, Vmax = 6.1 X 10(-12) mol.mg-1.min-1] carrier for pGlu-His in renal brush-border membrane vesicles. In the present study, we sought to demonstrate that multiple carriers exist for the transport of a single dipeptide by determining whether a low-affinity carrier also exists for the uptake of pGlu-His. Transport of pGlu-His into brush-border membrane vesicles was saturable over the concentration range of 10(-5)-10(-3) M, yielding a Kt of 6.3 X 10(-5) M and a Vmax of 2.2 X 10(-10) mol.mg-1.min-1. Uptake was inhibited by the dipeptides glycyl-proline, glycyl-sarcosine, and carnosine but not by the tripeptide pyroglutamyl-histidyl-prolinamide. We conclude that 1) pGlu-His is transported across the luminal membrane of the proximal tubule by multiple carriers and 2) the lower affinity carrier, unlike the higher affinity carrier, is nonspecific with respect to other dipeptides.

Sign in / Sign up

Export Citation Format

Share Document