scholarly journals Effective Small Interfering RNA Therapy to Treat CLCN7-dependent Autosomal Dominant Osteopetrosis Type 2

2015 ◽  
Vol 4 ◽  
pp. e248 ◽  
Author(s):  
Mattia Capulli ◽  
Antonio Maurizi ◽  
Luca Ventura ◽  
Nadia Rucci ◽  
Anna Teti
Keyword(s):  
Small Interfering Rna ◽  
Autosomal Dominant ◽  
Interfering Rna ◽  
Autosomal Dominant Osteopetrosis

New experimental small interfering RNA therapy for autosomal dominant osteopetrosis

Bone ◽  
2010 ◽  
Vol 47 ◽  
pp. S48
Author(s):  
M. Capannolo⁎ ◽  
N. Rucci ◽  
A. Teti ◽  
A. Del Fattore
Keyword(s):  
Small Interfering Rna ◽  
Autosomal Dominant ◽  
Interfering Rna ◽  
Autosomal Dominant Osteopetrosis

Radiographic imaging, densitometry and disease severity in Autosomal dominant osteopetrosis type 2

2020 ◽  
Author(s):  
Lauren M. Ladd ◽  
Erik A. Imel ◽  
Paul J. Niziolek ◽  
Ziyue Liu ◽  
Stuart J. Warden ◽  
...  
Keyword(s):  
Disease Severity ◽  
Autosomal Dominant ◽  
Radiographic Imaging ◽  
Autosomal Dominant Osteopetrosis

scholarly journals Transcriptome analysis reveals potential biomarkers of CLCN7-dependent Autosomal Dominant Osteopetrosis Type 2 (ADO2)

Bone Reports ◽  
2020 ◽  
Vol 13 ◽  
pp. 100657
Author(s):  
Iona Norwood ◽  
Denis Szondi ◽  
Nadia Rucci ◽  
Anna Teti ◽  
Antonio Maurizi
Keyword(s):  
Transcriptome Analysis ◽  
Autosomal Dominant ◽  
Potential Biomarkers ◽  
Autosomal Dominant Osteopetrosis

Analysis of variation in expression of autosomal dominant osteopetrosis type 2: Searching for modifier genes

Bone ◽  
2005 ◽  
Vol 37 (5) ◽  
pp. 655-661 ◽  
Author(s):  
Kang Chu ◽  
Daniel L. Koller ◽  
Richard Snyder ◽  
Tonya Fishburn ◽  
Dongbing Lai ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Modifier Genes ◽  
Analysis Of Variation ◽  
Autosomal Dominant Osteopetrosis

scholarly journals Adiponectin Ameliorates Lung Ischemia-Reperfusion Injury Through SIRT1-Pink1 Signaling-Mediated Mitophagy in Type 2 Diabetic Rats

2021 ◽  
Author(s):  
Tao Jiang ◽  
Tianhua Liu ◽  
Xijin Deng ◽  
Wengang Ding ◽  
Ziyong Yue ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Transplantation ◽  
Protective Effect ◽  
Mitochondrial Dysfunction ◽  
Small Interfering Rna ◽  
Ischemia Reperfusion ◽  
Diabetic Rats ◽  
Interfering Rna ◽  
Type 2 Diabetic

Abstract BackgroundDiabetes mellitus (DM) is a key contributing factor to the poor survival in lung transplantation recipients. Mitochondrial dysfunction is recognized as a critical mediator in the pathogenesis of diabetic lung ischemia-reperfusion (IR) injury. The protective effects of adiponectin have been demonstrated in our previously study, but the underlying mechanism remained unclear. Here we demonstrated an important role of mitophagy in the protective effect of adiponectin during diabetic lung IR injury.Methods High-fat diet-fed streptozotocin-induced type 2 diabetic rats as recipients were exposed to adiponectin with or without administration of the SIRT1 inhibitor EX527 following lung transplantation. To unravel the mechanisms underlying the action of adiponectin, rat pulmonary microvascular endothelial cells were transfected with SIRT1 small-interfering RNA or Pink1 small-interfering RNA and then subjected to in vitro diabetic lung IR injury.ResultsMitophagy was impaired in the diabetic lung subjected to IR injury, accompanied by increased oxidative stress, inflammation, apoptosis, and mitochondrial dysfunction. Adiponectin induced mitophagy and attenuated subsequent diabetic lung IR injury by improving lung functional recovery, suppressing oxidative damage, diminishing inflammation, decreasing cell apoptosis, and preserving mitochondrial function. However, both inhibitors of mitophagy and knockdown of Pink1 suppressed mitophagy, and reduced the protective action of adiponectin. Furthermore, we demonstrated that APN affected Pink1 stabilization via the SIRT1 signaling pathway, and knockdown of SIRT1 suppressed Pink1 expression and compromised the protective effect of adiponectin.ConclusionThese data demonstrated that adiponectin attenuated reperfusion-induced oxidative stress, inflammation, apoptosis and mitochondrial dysfunction via activation of SIRT1-Pink1 signaling-mediated mitophagy in diabetic lung IR injury.

scholarly journals Enhanced p22phox expression impairs vascular function through p38 and ERK1/2 MAP kinase-dependent mechanisms in type 2 diabetic mice

2014 ◽  
Vol 306 (7) ◽  
pp. H972-H980 ◽  
Author(s):  
Modar Kassan ◽  
Soo-Kyoung Choi ◽  
Maria Galán ◽  
Young-Ho Lee ◽  
Mohamed Trebak ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Nadph Oxidase ◽  
Vascular Function ◽  
Small Interfering Rna ◽  
Diabetic Mice ◽  
Mitogen Activated Protein ◽  
Ros Scavenger ◽  
Interfering Rna ◽  
Type 2 Diabetic

Type 2 diabetes is associated with vascular complication. We hypothesized that increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit p22 phox expression impairs vascular endothelium-dependent relaxation (EDR) in type 2 diabetes. Type 2 diabetic ( db − /db −) and control ( db − /db +) mice were treated with reactive oxygen species (ROS) scavenger, polyethylene glycol superoxide dismutase (1,000 U/kg daily ip), or small interfering RNA p22 phox (p22 phox-lentivirus-small interfering RNA, 100 μg iv, 2 times/wk) for 1 mo. EDR was impaired in microvascular bed (coronary arteriole and femoral and mesenteric resistance arteries) from diabetic mice compared with control. Interestingly, ROS scavenger and p22 phox downregulation did not affect blood glucose level or body weight but significantly improved EDR. Mitogen-activated protein kinases (ERK1/2 and p38) phosphorylation and NADPH oxidase activity were increased in arteries from diabetic mice and were reduced after ROS scavenger or p22 phox downregulation in db − /db − mice. The present study showed that enhanced p22 phox expression causes vascular dysfunction through ERK1/2 and p38-mitogen-activated protein kinase-dependent mechanisms in male type 2 diabetic mice. Therefore, p22 phox could be an important target to improve vascular function in diabetes.

scholarly journals Adeno-Associated Virus Small Rep Proteins Are Modified with at Least Two Types of Polyubiquitination

2009 ◽  
Vol 84 (2) ◽  
pp. 1206-1211 ◽  
Author(s):  
K. David Farris ◽  
Olufemi Fasina ◽  
Loretta Sukhu ◽  
Long Li ◽  
David J. Pintel
Keyword(s):  
Small Interfering Rna ◽  
Adenovirus Type ◽  
Proteasomal Degradation ◽  
Transient Transfection ◽  
Adeno Associated Virus ◽  
Rep Proteins ◽  
Cullin 5 ◽  
Interfering Rna ◽  
Adenovirus Type 5

ABSTRACT Adeno-associated virus (AAV) type 2 and 5 proteins Rep52 and Rep40 were polyubiquitinated during AAV-adenovirus type 5 (Ad5) coinfection and during transient transfection in either the presence or absence of Ad5 E4orf6 and E1b-55k. Polyubiquitination of small Rep proteins via lysine 48 (K48) linkages, normally associated with targeting of proteins for proteasomal degradation, was detected only in the presence of E4orf6. The small Rep proteins were ubiquitinated via lysine 63 (K63) following transfection in either the presence or absence of E4orf6 or following coinfection with Ad5. E4orf6/E1b-55k-dependent K48-specific polyubiquitination of small Rep proteins could be inhibited using small interfering RNA (siRNA) to cullin 5.

scholarly journals Adiponectin ameliorates lung ischemia–reperfusion injury through SIRT1-PINK1 signaling-mediated mitophagy in type 2 diabetic rats

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Tao Jiang ◽  
Tianhua Liu ◽  
Xijin Deng ◽  
Wengang Ding ◽  
Ziyong Yue ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Transplantation ◽  
Protective Effect ◽  
Mitochondrial Dysfunction ◽  
Small Interfering Rna ◽  
Ischemia Reperfusion ◽  
Diabetic Rats ◽  
Interfering Rna ◽  
Type 2 Diabetic

Abstract Background Diabetes mellitus (DM) is a key contributing factor to poor survival in lung transplantation recipients. Mitochondrial dysfunction is recognized as a critical mediator in the pathogenesis of diabetic lung ischemia–reperfusion (IR) injury. The protective effects of adiponectin have been demonstrated in our previous study, but the underlying mechanism remains unclear. Here we demonstrated an important role of mitophagy in the protective effect of adiponectin during diabetic lung IR injury. Methods High-fat diet-fed streptozotocin-induced type 2 diabetic rats were exposed to adiponectin with or without administration of the SIRT1 inhibitor EX527 following lung transplantation. To determine the mechanisms underlying the action of adiponectin, rat pulmonary microvascular endothelial cells were transfected with SIRT1 small-interfering RNA or PINK1 small-interfering RNA and then subjected to in vitro diabetic lung IR injury. Results Mitophagy was impaired in diabetic lungs subjected to IR injury, which was accompanied by increased oxidative stress, inflammation, apoptosis, and mitochondrial dysfunction. Adiponectin induced mitophagy and attenuated subsequent diabetic lung IR injury by improving lung functional recovery, suppressing oxidative damage, diminishing inflammation, decreasing cell apoptosis, and preserving mitochondrial function. However, either administration of 3-methyladenine (3-MA), an autophagy antagonist or knockdown of PINK1 reduced the protective action of adiponectin. Furthermore, we demonstrated that APN affected PINK1 stabilization via the SIRT1 signaling pathway, and knockdown of SIRT1 suppressed PINK1 expression and compromised the protective effect of adiponectin. Conclusion These data demonstrated that adiponectin attenuated reperfusion-induced oxidative stress, inflammation, apoptosis and mitochondrial dysfunction via activation of SIRT1- PINK1 signaling-mediated mitophagy in diabetic lung IR injury.

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