scholarly journals Knockdown of hypoxia-inducible factor 1-alpha (HIF1α) interferes with angiopoietin-like protein 2 (ANGPTL2) to attenuate high glucose-triggered hypoxia/reoxygenation injury in cardiomyocytes

Bioengineered ◽  
2022 ◽  
Vol 13 (1) ◽  
pp. 1476-1490
Author(s):  
Weiguo Chen ◽  
Jianbang Wang ◽  
Xihui Wang ◽  
Pan Chang ◽  
Meng Liang
Keyword(s):  
High Glucose ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1 ◽  
Reoxygenation Injury ◽  
Hypoxia Reoxygenation

scholarly journals Sevoflurane Postconditioning Attenuates Hypoxia/Reoxygenation Injury of Cardiomyocytes Under High Glucose by Regulating HIF-1α/MIF/AMPK Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Haiping Ma ◽  
Yongjie Li ◽  
Tianliang Hou ◽  
Jing Li ◽  
Long Yang ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Protective Effect ◽  
Cell Viability ◽  
Mrna Expression ◽  
High Glucose ◽  
Mitochondrial Membrane ◽  
Ampk Signaling ◽  
H9c2 Cardiomyocytes ◽  
Reoxygenation Injury ◽  
Hypoxia Reoxygenation

Subject: Cardiovascular disease, as a very common and serious coexisting disease in diabetic patients, and is one of the risk factors that seriously affect the prognosis and complications of surgical patients. Previous studies have shown that sevoflurane post-conditioning (SPostC) exerts a protective effect against myocardial ischemia/reperfusion injury by HIF-1α, but the protective effect is weakened or even disappeared under hyperglycemia. This study aims to explore whether regulating the HIF-1α/MIF/AMPK signaling pathway can restore the protective effect and reveal the mechanism of SPostC on cardiomyocyte hypoxia/reoxygenation injury under high glucose conditions.Methods: H9c2 cardiomyocytes were cultured in normal and high-concentration glucose medium to establish a hypoxia/reoxygenation (H/R) injury model of cardiomyocytes. SPostC was performed with 2.4% sevoflurane for 15 min before reoxygenation. Cell damage was determined by measuring cell viability, lactate dehydrogenase activity, and apoptosis; Testing cell energy metabolism by detecting reactive oxygen species (ROS) generation, ATP content and mitochondrial membrane potential; Analysis of the change of HIF-1α, MIF and AMPKα mRNA expression by RT-PCR. Western blotting was used to examine the expression of HIF-1α, MIF, AMPKα and p-AMPKα proteins. HIF-1α and MIF inhibitors and agonists were administered 40 min before hypoxia.Results: 1) SPostC exerts a protective effect by increasing cell viability, reducing LDH levels and cell apoptosis under low glucose (5 μM) after undergoing H/R injury; 2) High glucose concentration (35 μM) eliminated the cardioprotective effect of SPostC, which is manifested by a significantly decrease in the protein and mRNA expression level of the HIF-1α/MIF/AMPK signaling pathway, accompanied by decreased cell viability, increased LDH levels and apoptosis, increased ROS production, decreased ATP synthesis, and decreased mitochondrial membrane potential; 3. Under high glucose (35 μM), the expression levels of HIF-1α and MIF were up-regulated by using agonists, which can significantly increase the level of p-AMPKα protein, and the cardioprotective effect of SPostC was restored.Conclusion: The signal pathway of HIF-1α/MIF/AMPK of H9c2 cardiomyocytes may be the key point of SPostC against H/R injure. The cardioprotective of SPostC could be restored by upregulating the protein expression of HIF-1α and MIF under hyperglycemia.

scholarly journals THE PRELIMINARY STUDY OF PROTECTIVE INFLUENCE OF HYPOXIA INDUCIBLE FACTOR-1 (HIF-1) ON CULTURED CARDIOCYTES WITH HYPOXIA—REOXYGENATION (H/R)

Heart ◽  
2012 ◽  
Vol 98 (Suppl 2) ◽  
pp. E58.1-E58
Author(s):  
Xiaoli Shen ◽  
Feng Chen ◽  
Lili Han ◽  
Fangfang Ma ◽  
Saimei Lin ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1 ◽  
Preliminary Study ◽  
Hypoxia Reoxygenation

scholarly journals Overexpression of DJ-1 reduces oxidative stress and attenuates hypoxia/reoxygenation injury in NRK-52E cells exposed to high glucose

2016 ◽  
Vol 38 (3) ◽  
pp. 729-736 ◽  
Author(s):  
Zi-Ying Shen ◽  
Qian Sun ◽  
Zhong-Yuan Xia ◽  
Qing-Tao Meng ◽  
Shao-Qing Lei ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Glucose ◽  
Reoxygenation Injury ◽  
Hypoxia Reoxygenation

scholarly journals Sevoflurane postconditioning alleviates hypoxia-reoxygenation injury of cardiomyocytes by promoting mitochondrial autophagy through the HIF-1/BNIP3 signaling pathway

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7165 ◽  
Author(s):  
Long Yang ◽  
Jianjiang Wu ◽  
Peng Xie ◽  
Jin Yu ◽  
Xin Li ◽  
...  
Keyword(s):  
Cell Viability ◽  
Signaling Pathway ◽  
Cell Damage ◽  
Hypoxia Inducible Factor ◽  
Protective Effects ◽  
Interacting Protein ◽  
Lactate Dehydrogenase Activity ◽  
Reoxygenation Injury ◽  
Sevoflurane Postconditioning ◽  
Hypoxia Reoxygenation

Background Sevoflurane postconditioning (SpostC) can alleviate hypoxia-reoxygenation injury of cardiomyocytes; however, the specific mechanism remains unclear. This study aimed to investigate whether SpostC promotes mitochondrial autophagy through the hypoxia-inducible factor-1 (HIF-1)/BCL2/adenovirus E1B 19-kDa-interacting protein 3 (BNIP3) signaling pathway to attenuate hypoxia-reoxygenation injury in cardiomyocytes. Methods The H9C2 cardiomyocyte hypoxia/reoxygenation model was established and treated with 2.4% sevoflurane at the beginning of reoxygenation. Cell damage was determined by measuring cell viability, lactate dehydrogenase activity, and apoptosis. Mitochondrial ultrastructural and autophagosomes were observed by transmission electron microscope. Western blotting was used to examine the expression of HIF-1, BNIP3, and Beclin-1 proteins. The effects of BNIP3 on promoting autophagy were determined using interfering RNA technology to silence BNIP3. Results Hypoxia-reoxygenation injury led to accumulation of autophagosomes in cardiomyocytes, and cell viability was significantly reduced, which seriously damaged cells. Sevoflurane postconditioning could upregulate HIF-1α and BNIP3 protein expression, promote autophagosome clearance, and reduce cell damage. However, these protective effects were inhibited by 2-methoxyestradiol or sinBNIP3. Conclusion Sevoflurane postconditioning can alleviate hypoxia-reoxygenation injury in cardiomyocytes, and this effect may be achieved by promoting mitochondrial autophagy through the HIF-1/BNIP3 signaling pathway.

scholarly journals HIF-1 mediated activation of antimicrobial peptide LL-37 in type 2 diabetic patients

2021 ◽  
Author(s):  
Soumitra Mohanty ◽  
Witchuda Kamolvit ◽  
Silvia Zambrana ◽  
Eduardo Gonzales ◽  
Jonas Tovi ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
High Glucose ◽  
Bacterial Load ◽  
Hypoxia Inducible Factor ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Hypoxia Inducible Factor 1 ◽  
Uroepithelial Cells ◽  
Type 2 Diabetic

Abstract Infections are common in patients with diabetes, but increasing antibiotic resistance hampers successful bacterial clearance and calls for alternative treatment strategies. Hypoxia-inducible factor 1 (HIF-1) is known to influence the innate immune defense and could therefore serve as a possible target. However, the impact of high glucose on HIF-1 has received little attention and merits closer investigation. Here, we show that higher levels of proinflammatory cytokines and CAMP, encoding for the antimicrobial peptide cathelicidin, LL-37, correlate with HIF-1 in type 2 diabetic patients. Chemical activation of HIF-1 further enhanced LL-37, IL-1β, and IL-8 in human uroepithelial cells exposed to high glucose. Moreover, HIF-1 activation of transurethrally infected diabetic mice resulted in lower bacterial load. Drugs activating HIF-1 could therefore in the future potentially have a therapeutic role in clearing bacteria in diabetic patients with infections where antibiotic treatment failed. Key messages • Mohanty et al. “HIF-1 mediated activation of antimicrobial peptide LL-37 in type 2 diabetic patients.” • Our study highlights induction of the antimicrobial peptide, LL-37, and strengthening of the innate immunity through hypoxia-inducible factor 1 (HIF-1) in diabetes. • Our key observations are: 1. HIF-1 activation increased LL-37 expression in human urothelial cells treated with high glucose. In line with that, we demonstrated that patients with type 2 diabetes living at high altitude had increased levels of the LL-37. 2. HIF-1 activation increased IL-1β and IL-8 in human uroepithelial cells treated with high glucose concentration. 3. Pharmacological activation of HIF-1 decreased bacterial load in the urinary bladder of mice with hereditary diabetes. • We conclude that enhancing HIF-1 may along with antibiotics in the future contribute to the treatment in selected patient groups where traditional therapy is not possible.

Sign in / Sign up

Export Citation Format

Share Document