Acute Hyperglycemia May Induce Renal Tubular Injury Through Mitophagy Inhibition

Wang, Jingyu; Yue, Xiaodan; Meng, Cheng; Wang, Ziyan; Jin, Xiaofang; Yang, Juhong; Shan, Chunyan; Gao, Zhongai; Yang, Yanhui; Li, Jing; Bai, Chang; Chang, Baocheng

doi:10.3389/fendo.2020.536213

Cited by 22 publications

(13 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This indicated that HG induced autophagy in MDBK cells. These results are consistent with previous findings [ 31 , 32 , 33 ]. Several evolutionarily-conserved genes (called autophagy-related genes, such as LC3, Beclin1, and p62) are involved in the process of autophagy [ 35 , 36 , 37 ].…”

Section: Discussionsupporting

confidence: 94%

“…Moreover, autophagy plays an important regulatory role in HG-induced renal cell injury [ 30 ]. The glucose concentration in vitro is generally 5.5 mM~25.5 mM, which is used to simulate normal blood glucose and hyperglycemia respectively [ 31 , 32 ]. Furthermore, blood glucose levels in beef cattle subjected to transport stress increased from 5.5 mM to 15.2 mM [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Notch3-Mediated mTOR Signaling Pathway Is Involved in High Glucose-Induced Autophagy in Bovine Kidney Epithelial Cells

et al. 2022

View full text Add to dashboard Cite

It is reported that Notch3 and mTOR signaling pathways are involved in autophagy, and both can be activated by high glucose (HG). However, the relationship between Notch3 and mTOR and how Notch3 affects mTOR to regulate HG-induced autophagy in bovine kidney epithelial cells is still unclear. The purpose of this study is to explore how Notch3 affects mTOR to modulate HG-induced autophagy in bovine kidney cells. Our results showed that HG treatment significantly decreased the cell viability of MDBK cells in a dose-dependent manner. HG treatment significantly increased the expression of LC3-II/I ratio and Beclin1 protein and significantly decreased the expression of p62 protein. Consistently, LC3 fluorescence signal formation was detected by immunofluorescence in both dose and time-dependent manners. In addition, HG treatment significantly increased the expression of Notch3 protein and decreased the expression of the p-mTOR protein in both dose and time-dependent manners. Inhibition of Notch3 upregulated the expression of p-mTOR and p62 protein, and downregulated the expression of LC3-II/I ratio and Beclin1 protein. Besides, the function of Notch3 was investigated. In this study, inhibition of Notch3 activity significantly increased the viability of HG-stimulated MDBK cells. In summary, our results revealed that the Notch3-mediated mTOR signaling pathway was involved in HG-induced autophagy in MDBK cells.

show abstract

Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Notch3-Mediated mTOR Signaling Pathway Is Involved in High Glucose-Induced Autophagy in Bovine Kidney Epithelial Cells

et al. 2022

View full text Add to dashboard Cite

show abstract

“…However, BU increased after one week indicating AKI without chronic glomerular endothelial cell injury [52]. Acute hyperglycemia could cause AKI and tubular injury and leads to oxidative stress [53]. The data presented showed that severe hyperglycemia was obtained two days after STR administration, which might play a role in inducing AKI, proteinuria, and a considerable decrease in the urinary excretion of creatinine, BU, uric acid, phosphorous, and magnesium.…”

Section: Effect Of the Intervention On Liver Enzymes Lipids And Hemog...mentioning

confidence: 81%

Arbutus Unedo Honey and Propolis Ameliorate Acute Kidney Injury, Acute Liver Injury, and Proteinuria via Hypoglycemic and Antioxidant Activity in Streptozotocin-Treated Rats

Touzani

Al-Waili

Imtara

et al. 2022

Cell Physiol Biochem

View full text Add to dashboard Cite

BACKGROUND/AIMS: Honey and propolis have biological and therapeutic effects in various pathological and clinical conditions such as hyperglycemia and diabetes. However, the combined use of honey and propolis has not been reported. The study evaluated the protective effect of Arbutus unedo honey, propolis and their combination in streptozotocin (STR)-induced hyperglycemia, acute kidney injury (AKI), liver injury, dyslipidemia, and proteinuria in male Wistar rats. METHODS: The study identified physicochemical characteristics, mineral and antioxidant content, and antioxidant activity in honey and propolis. Rats were assigned to five groups, with five rats in each group; control, STR-treated, STR-treated + honey (1g/kg/day), STR-treated + propolis (100 mg/day), and STR-treated + honey and propolis. On day 15, blood glucose, insulin, HBA1c, kidney function tests, liver enzymes, lipid profile, hemoglobin, and urine protein, creatinine, glucose, and electrolytes were analyzed. Liver, pancreas, and kidney tissues were studied histologically. The mineral component in honey and propolis was determined by atomic absorption spectrometry. Honey analysis was performed by HPLC. Chemical characterization of propolis was performed by LC/DAD/ESI-MSn . Measurement of blood and urine parameters was carried out with an automated analyzer (Architect c8000) and XT-1800i Automated Hematology Analyzer. Insulin concentration was determined by Elisa and insulin resistance was estimated by using HOMA-IR. RESULTS: Honey and propolis contain a high quantity of antioxidants and exhibit in vitro antioxidant activity. In STR-treated rats, blood glucose, HBA1c, creatinine, blood urea, liver enzymes, and urine protein significantly increased compared to the control group (P<0.05), while insulin, hemoglobin, and body weight significantly decreased. Histological changes were evident in the pancreas, kidney, and liver tissues. These results indicated AKI, liver injury, and pancreatic injury, which was evident with reducing the number of the island of Langerhans and marked hyperglycemia. The use of honey and propolis significantly (P<0.05) attenuated liver and kidney injury, and proteinuria, and improved level of hemoglobin, HBA1c, and insulin toward the normal range. The combination of honey and propolis was more effective than honey or propolis individually (P<0.05). CONCLUSION: the combination of propolis and honey can prevent STR-induced AKI, liver injury, proteinuria, dyslipidemia, anemia, hyperglycemia, and body weight loss, most likely by their hypoglycemic and antioxidant activities.

show abstract

“…Collectively they provide evidence α7nAChR agonists may be useful in preventing DN. Hyperglycemia contributes to the development of ROS, oxidant stress and apoptosis in renal tubular cells [23][24][25] . Apoptosis of renal tubular epithelial cells leads to the loss of intrinsic cells in the kidney resulting in kidney damage and decreased renal function.…”

Section: Discussionmentioning

confidence: 99%

GTS-21, a selective alpha7 nicotinic acetylcholine receptor agonist, ameliorates diabetic nephropathy in Lepr db/db mice

Meng

Tian

et al. 2022

Preprint

View full text Add to dashboard Cite

Background Diabetic nephropathy (DN) is a serious complicating factor in human type 2 diabetes (T2DM), and it commonly results in end-stage renal disease (ESRD) that requires kidney dialysis. Here, we report that the α7 nicotinic acetylcholine receptor (α7nAChR) agonist GTS-21 exerts a novel anti-inflammatory action to ameliorate DN, as studied using an inbred strain of Leprdb/db mice in which hyperglycemia and obesity co-exist owing to defective leptin receptor (Lepr) signaling. Methods For this analysis, GTS-21 was administered to 10–12 week-old male and female mice as a 4mg/kg intraperitoneal injection, twice-a-day, for 8 weeks. Kidney function and injury owing to DN were monitored by determination of plasma levels of BUN, creatinine, KIM-1 and NGAL. Histologic analysis of glomerular hypertrophy and mesangial matrix expansion were also used to assess DN in these mice. Concurrently, renal inflammation was assessed by measuring IL-6 and HMGB1, while also quantifying renal cell apoptosis, and apoptotic signaling pathways. Results We found that Leprdb/db mice exhibited increased markers of BUN, creatinine, NGAL, KIM-1, IL-6, cytochrome C, and HMGB-1. These abnormalities were also accompanied by histologic kidney injury (mesangial matrix expansion and apoptosis). Remarkably, all such pathologies were significantly reduced by GTS-21. Conclusions Collectively, our results provide new evidence that the α7nAChR agonist GTS-21 has the ability to attenuate diabetes-induced kidney injury. Potentially, GTS-21 engages the vagus nerve cholinergic anti-inflammatory reflex pathway (CAP) to produce this beneficial effect.

show abstract

Acute Hyperglycemia May Induce Renal Tubular Injury Through Mitophagy Inhibition

Cited by 22 publications

References 39 publications

Notch3-Mediated mTOR Signaling Pathway Is Involved in High Glucose-Induced Autophagy in Bovine Kidney Epithelial Cells

Notch3-Mediated mTOR Signaling Pathway Is Involved in High Glucose-Induced Autophagy in Bovine Kidney Epithelial Cells

Arbutus Unedo Honey and Propolis Ameliorate Acute Kidney Injury, Acute Liver Injury, and Proteinuria via Hypoglycemic and Antioxidant Activity in Streptozotocin-Treated Rats

GTS-21, a selective alpha7 nicotinic acetylcholine receptor agonist, ameliorates diabetic nephropathy in Lepr db/db mice

Contact Info

Product

Resources

About