Endoplasmic reticulum stress and its effects on renal tubular cells apoptosis in ischemic acute kidney injury

Xu, Yan; Guo, Min; Jiang, Wei; Dong, Hui; Han, Yijing; An, Xiaofei; Zhang, Jisheng

doi:10.3109/0886022x.2016.1160724

Cited by 58 publications

(39 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Here, our results suggested that impairment of autophagy induced by SUs might also contribute to the apoptosis of PTECs. In addition, our results are consistent with previous observations that autophagy protects PTECs from injury and apoptosis (Dong et al 2015; Xu et al 2016). Other research indicates that increased cytosolic Ca 2+ levels regulated by K ATP channels play a role in impairing autophagy, which is associated with neurodegenerative disorders (Hambrock et al 2006).…”

Section: Discussionsupporting

confidence: 93%

Different sulfonylureas induce the apoptosis of proximal tubular epithelial cell differently via closing KATP channel

Zhang

Zhou

Shen

et al. 2018

Mol Med

View full text Add to dashboard Cite

BackgroundSulfonylureas (SUs) are widely prescribed for the treatment of type 2 diabetes (T2DM). Sulfonylurea receptors (SURs) are their main functional receptors. These receptors are also found in kidney, especially the tubular cells. However, the effects of SUs on renal proximal tubular epithelial cells (PTECs) were unclear.MethodsThree commonly used SUs were included in this study to investigate if different SUs have different effects on the apoptosis of PTECs. HK-2 cells were exposed to SUs for 24 h prior to exposure to 30 mM glucose, the apoptosis rate was evaluated by Annexin/PI flow cytometry. Bcl-2, Bax and the ratio of LC3II to LC3I were also studied by western blot in vitro. Diazoxide was used to evaluate the role of KATP channel in SUs-induced apoptosis of PTECs. A Student’s t-test was used to assess significance for data within two groups.ResultsTreatment with glibenclamide aggravated the apoptosis of HK-2 cells in high-glucose, as indicated by a significant decrease in the expression of Bcl-2 and increase in Bax. Additionally, the decreased LC3II/LC3I reflects that the autophagy was inhibited by glibenclamide. Similar but less pronounced change was found in glimepiride group, however, nearly opposite effects were found in gliclazide group. Further, the effects of glibenclamide on apoptosis promotion and the decreased LC3II/LC3I were ameliorated obviously by treatment with 100uM diazoxide. The potential protection effect of gliclazide was also inhibited after opening the KATP channel.ConclusionOur results suggest that, the effects of glibenclamide and glimepiride on PTECs apoptosis, especially the former, were achieved in part by closing the KATP channel. In contrast to glibenclamide and glimepiride, therapeutic concentrations of gliclazide showed an inhibitory effect on apoptosis of PTECs, which may have a benefit in the preservation of functional PTECs mass.

show abstract

Section: Discussionsupporting

confidence: 93%

Different sulfonylureas induce the apoptosis of proximal tubular epithelial cell differently via closing KATP channel

Zhang

Zhou

Shen

et al. 2018

Mol Med

View full text Add to dashboard Cite

show abstract

“…When the balance breaks down within a variety of environmental insults including hypoxia, oxidative stress, and cell starvation, unfolded and malfolded proteins are unable to transport from ER lumen to other parts of cells or space out of cells and then loaded in the ER to trigger ER stress [9]. With the injury lasting long and progressing, ER stress known as prodeath pathway will result in apoptosis and other responses [10]. …”

Section: Introductionmentioning

confidence: 99%

7,8-DHF Treatment Induces Cyr61 Expression to Suppress Hypoxia Induced ER Stress in HK-2 Cells

Zhang

Liu

et al. 2016

BioMed Research International

Self Cite

View full text Add to dashboard Cite

Acute kidney injury (AKI) is a common syndrome which is strongly linked to high morbidity and mortality. Hypoxia is the leading cause of AKI and the proximal renal tubular cells are the most damaged part in the kidney during this period. It has been observed that 7,8-dihydroxyflavone (7,8-DHF) plays a protective role by acting on antiapoptosis and antioxidative stress. In this study we explored functions of 7,8-DHF in protecting human proximal tubular cell line HK-2 from hypoxia insults. We observed that treatment of 7,8-DHF could improve the viability of ischemic cell. Mechanistically, we found that 7,8-DHF could elevate the expression of cysteine-rich protein 61 (Cyr61), a protective immediate early gene in AKI. In addition, treatment of 7,8-DHF decreased CCAAT/enhancer-binding protein homologous protein (CHOP) expression, which is a marker protein during endoplasmic reticulum (ER) stress activation. Intriguingly, overexpression of Cyr61 significantly reduced CHOP expression. Taken together, our results provide novel insights into the possible protective role of 7,8-DHF by activating Cyr61 signaling and suppressing ER stress in hypoxic HK-2 cells which have potential clinical implications for the treatment of AKI.

show abstract

“…In this study, we disclosed that apoptosis was the major mechanism contributing to the liver injury after transplantation [21-23]. Most importantly, UA pretreatment could alleviate the apoptosis [24]. There are a lot of studies confirmed the role of ERS in ischemia reperfusion injury after liver transplantation [25, 26]_ENREF_22_ENREF_1.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, we also detected the expressions of apoptosis-related regulators. Caspase-3 is an apoptosis effector and the high level of caspase-3 indicates the increased apoptosis [24, 28]_ENREF_1. Although we also observed obvious apoptosis in UA treated group, this drug could increase the resistance of the transplanted livers.…”

Section: Discussionmentioning

confidence: 99%

Ursolic Acid Improves Liver Transplantation and Inhibits Apoptosis in Miniature Pigs Using Donation After Cardiac Death

Zhou

Cheng

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background: Ursolic acid (UA) possesses extensive pharmacological activities, including anti-oxidation, anti-infection, anti-inflammation, anti-tumor, liver protection. This study was designed to investigate the effect of UA on liver transplantation after liver transplantation using donation after cardiac death (DCD), and to assess the mechanisms. Methods: 24 healthy experimental pigs were randomly divided into control and experimental groups. Each group received six DCD liver transplantations. In the experimental group, the recipient pigs received 120 mg/kg UA 4 h before surgery by intraperitoneal injection. The liver tissues and vein blood were collected 0 h, 1 h, 3 h, 6 h, 12 h and 24 h after transplantation. Morphological change, malondialdehyde (MDA) level, protein kinase-like ER kinase (PERK)-CHOP signaling pathway and apoptosis in liver tissue and serum aminotransferase (ALT) level were assessed. Results: Compared with control group, ALT level was significantly decreased (P<0.05) and pathological changes in liver were ameliorated in experimental group. UA treatment also decreased MDA level in liver tissue and attenuated the apoptosis. Compared with control group, Bax decreased and Bcl-2 increased in UA-treated group. Importantly, UA decreased p-PERK, PERK, p-eIF2α, eIF2α, ATF4 and CHOP levels compared with control group. Conclusion: Our results showed that UA treatment could improve the DCD liver transplantation likely through inhibiting apoptosis and PERK-CHOP pathway.

show abstract

Endoplasmic reticulum stress and its effects on renal tubular cells apoptosis in ischemic acute kidney injury

Cited by 58 publications

References 52 publications

Different sulfonylureas induce the apoptosis of proximal tubular epithelial cell differently via closing KATP channel

Different sulfonylureas induce the apoptosis of proximal tubular epithelial cell differently via closing KATP channel

7,8-DHF Treatment Induces Cyr61 Expression to Suppress Hypoxia Induced ER Stress in HK-2 Cells

Ursolic Acid Improves Liver Transplantation and Inhibits Apoptosis in Miniature Pigs Using Donation After Cardiac Death

Contact Info

Product

Resources

About