In Vivo Effects of Silver Nanoparticles on Development, Behavior, and Mitochondrial Function are Altered by Genetic Defects in Mitochondrial Dynamics

2022 ◽  
Author(s):  
Danielle F. Mello ◽  
Laura L. Maurer ◽  
Ian T. Ryde ◽  
Dong Hoon Songr ◽  
Stella M. Marinakos ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Mitochondrial Function ◽  
Mitochondrial Dynamics ◽  
Genetic Defects ◽  
In Vivo Effects

scholarly journals The E3 ligase MARCH5 is a PPARγ target gene that regulates mitochondria and metabolism in adipocytes

2019 ◽  
Vol 316 (2) ◽  
pp. E293-E304 ◽  
Author(s):  
Simon T. Bond ◽  
Sarah C. Moody ◽  
Yingying Liu ◽  
Mete Civelek ◽  
Claudio J. Villanueva ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Mitochondrial Dynamics ◽  
Mouse Strains ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Metabolic Genes ◽  
And Function

Mitochondrial dynamics refers to the constant remodeling of mitochondrial populations by multiple cellular pathways that help maintain mitochondrial health and function. Disruptions in mitochondrial dynamics often lead to mitochondrial dysfunction, which is frequently associated with disease in rodents and humans. Consistent with this, obesity is associated with reduced mitochondrial function in white adipose tissue, partly via alterations in mitochondrial dynamics. Several proteins, including the E3 ubiquitin ligase membrane-associated RING-CH-type finger 5 (MARCH5), are known to regulate mitochondrial dynamics; however, the role of these proteins in adipocytes has been poorly studied. Here, we show that MARCH5 is regulated by peroxisome proliferator-activated receptor-γ (PPARγ) during adipogenesis and is correlated with fat mass across a panel of genetically diverse mouse strains, in ob/ob mice, and in humans. Furthermore, manipulation of MARCH5 expression in vitro and in vivo alters mitochondrial function, affects cellular metabolism, and leads to differential regulation of several metabolic genes. Thus our data demonstrate an association between mitochondrial dynamics and metabolism that defines MARCH5 as a critical link between these interconnected pathways.

scholarly journals Alpha-synuclein-induced mitochondrial dysfunction is mediated via a sirtuin 3-dependent pathway

2018 ◽  
Author(s):  
Jae-Hyeon Park ◽  
Marion Delenclos ◽  
Ayman H. Faroqi ◽  
Natasha N. DeMeo ◽  
Pamela J. McLean
Keyword(s):  
Parkinson Disease ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Mitochondrial Dynamics ◽  
Lewy Body Disease ◽  
Camp Response Element Binding ◽  
Protective Role ◽  
Alpha Synuclein ◽  
Sirtuin 3

AbstractThe sirtuins are highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent enzymes that play a broad role in cellular metabolism and aging. Mitochondrial sirtuin 3 (SIRT3) is downregulated in aging and age-associated diseases such as cancer and neuro-degeneration and plays a major role in maintaining mitochondrial function and preventing oxidative stress. Mitochondria dysfunction is central to the pathogenesis of Parkinson disease with mutations in mitochondrial-associated proteins such as PINK1 and parkin causing familial Parkinson disease. Here, we demonstrate that the presence of alpha-synuclein (αsyn) oligomers in mitochondria induce a corresponding decrease in mitochondrial SIRT3 activity and decreased mitochondrial biogenesis. We show that SIRT3 downregulation in the presence of αsyn accumulation is accompanied by increased phosphorylation of AMP-activated protein kinase (AMPK) and cAMP-response element binding protein (CREB), as well as increased phosphorylation of dynamin-related protein 1 (DRP1) and decreased levels of optic atrophy 1 (OPA1), which is indicative of impaired mitochondrial dynamics. Treatment with the AMPK agonist 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) restores SIRT3 expression and activity and improves mitochondrial function by decreasing αsyn oligomer formation. The accumulation of αsyn oligomers in mitochondria corresponds with SIRT3 down-regulation not only in an experimental cellular model, but also in vivo in a rodent model of Parkinson disease, and importantly, in human post mortem brains with neuropathologically confirmed Lewy body disease (LBD). Taken together our findings suggest that pharmacologically increasing SIRT3 levels will counteract αsyn-induced mitochondrial dysfunction by normalizing mitochondrial bioenergetics. These data support a protective role for SIRT3 in Parkinson disease-associated pathways and reveals significant mechanistic insight into the interplay of SIRT3 and αsyn.

scholarly journals Dynamin-Related Protein 1 Deficiency Promotes Recovery from AKI

2017 ◽  
Vol 29 (1) ◽  
pp. 194-206 ◽  
Author(s):  
Heather M. Perry ◽  
Liping Huang ◽  
Rebecca J. Wilson ◽  
Amandeep Bajwa ◽  
Hiromi Sesaki ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Mitochondrial Function ◽  
Ischemia Reperfusion Injury ◽  
Mitochondrial Dynamics ◽  
Ischemia Reperfusion ◽  
Mitochondrial Fission ◽  
Kidney Injury ◽  
Related Protein

The proximal tubule epithelium relies on mitochondrial function for energy, rendering the kidney highly susceptible to ischemic AKI. Dynamin-related protein 1 (DRP1), a mediator of mitochondrial fission, regulates mitochondrial function; however, the cell-specific and temporal role of DRP1 in AKI in vivo is unknown. Using genetic murine models, we found that proximal tubule–specific deletion of Drp1 prevented the renal ischemia-reperfusion–induced kidney injury, inflammation, and programmed cell death observed in wild-type mice and promoted epithelial recovery, which associated with activation of the renoprotective β-hydroxybutyrate signaling pathway. Loss of DRP1 preserved mitochondrial structure and reduced oxidative stress in injured kidneys. Lastly, proximal tubule deletion of DRP1 after ischemia-reperfusion injury attenuated progressive kidney injury and fibrosis. These results implicate DRP1 and mitochondrial dynamics as an important mediator of AKI and progression to fibrosis and suggest that DRP1 may serve as a therapeutic target for AKI.

The in vivo effects of silver nanoparticles on terrestrial isopods, Porcellio scaber, depend on a dynamic interplay between shape, size and nanoparticle dissolution properties

The Analyst ◽  
2019 ◽  
Vol 144 (2) ◽  
pp. 488-497 ◽  
Author(s):  
Sara Novak ◽  
Tea Romih ◽  
Barbara Drašler ◽  
Giovanni Birarda ◽  
Lisa Vaccari ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Porcellio Scaber ◽  
Terrestrial Isopods ◽  
Dissolution Properties ◽  
Low Concentrations ◽  
In Vivo Effects ◽  
Dynamic Interplay

The effects of exposure to low concentrations of AgNPs in model tissue, are the result of the interplay between size, shape and dissolution of ions from NPs.

In Vitro and in Vivo Effects of Dimethylnitrosamine on Mouse Liver Mitochondrial Function

1977 ◽  
Vol 154 (4) ◽  
pp. 530-533 ◽  
Author(s):  
M. A. Friedman ◽  
K. M. Watt ◽  
E. S. Higgins
Keyword(s):  
Mitochondrial Function ◽  
Mouse Liver ◽  
In Vivo Effects

scholarly journals Tang Luo Ning, a Traditional Chinese Compound Prescription, Ameliorates Schwannopathy of Diabetic Peripheral Neuropathy Rats by Regulating Mitochondrial Dynamics In Vivo and In Vitro

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiayue Zhu ◽  
Xinwei Yang ◽  
Xiao Li ◽  
Shuo Han ◽  
Yanbo Zhu ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Mitochondrial Function ◽  
Diabetic Peripheral Neuropathy ◽  
Mitochondrial Dynamics ◽  
Branch Length ◽  
Network Size ◽  
Mitofusin 2 ◽  
Atp Levels

Tang Luo Ning (TLN), a traditional Chinese compound prescription, has been used clinically to treat diabetic peripheral neuropathy (DPN) in China. However, the exact mechanisms remain unclear. The objective of this study is to unravel the effects of TLN on mitochondrial dynamics of DPN in streptozotocin-induced rat models and Schwann cells cultured in 150 mM glucose. Mitochondrial function was determined by Ca2+ and ATP levels of streptozotocin (STZ)-induced DPN rats and mitochondria structure, mitochondrial membrane potential (MMP), and mtDNA of high glucose incubated SCs. Mitochondrial dynamics protein including mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), optic atrophy 1 (Opa1), and dynamin-related protein 1 (Drp1) were investigated using Western blot or immunofluorescence. Myelin basic protein (MBP), myelin protein zero (MPZ), and sex-determining region Y (SRY)-box 10 (Sox10) were measured to represent schwannopathy. Our results showed that TLN increased ATP levels (0.38 of model, 0.69 of HTLN, 0.61 of LTLN, P＜0.01; 0.52 of 150 mM glucose, 1.00 of 10% TLN, P＜0.01, 0.94 of 1% TLN, P＜0.05), MMP (0.56 of 150 mM glucose, P＜0.01, 0.75 of 10% TLN, P＜0.05, 0.83 of 1% TLN, P＜0.01), and mtDNA (0.32 of 150 mM glucose, 0.43 of 10% TLN, P＜0.01) while decreased Ca2+ (1.54 of model, 1.06 of HTLN, 0.96 of LTLN, P＜0.01) to improve mitochondrial function in vivo and in vitro. TLN helps maintain balance of mitochondrial dynamics: it reduces the mitochondria number (1.60 of 150 mM glucose, 1.10 of 10% TLN, P＜0.01) and increases the mitochondria coverage (0.51 of 150 mM glucose, 0.80 of 10% TLN, 0.87 of 1% TLN, P＜0.01), mitochondrial network size (0.51 of 150 mM glucose, 0.95 of 10% TLN, 0.94 of 1% TLN, P＜0.01), and branch length (0.63 of 150 mM glucose, P＜0.01, 0.73 of 10% TLN, P＜0.05, 0.78 of 1% TLN, P＜0.01). Further, mitochondrial dynamics–related Mfn1 (0.47 of model, 0.82 of HTLN, 0.77 of LTLN, P＜0.01; 0.42 of 150 mM glucose, 0.56 of 10% TLN, 0.57 of 1% TLN, P＜0.01), Mfn2 (0.40 of model, 0.84 of HTLN, 0.63 of LTLN, P＜0.01; 0.46 of 150 mM glucose, 1.40 of 10% TLN, 1.40 of 1% TLN, P＜0.01), and Opa1 (0.58 of model, 0.71 of HTLN, 0.90 of LTLN, P＜0.01; 0.69 of 150 mM glucose, 0.96 of 10% TLN, 0.98 of 1% TLN, P＜0.05) were increased, while Drp1 (1.39 of model, 0.96 of HTLN, 1.18 of LTLN, P＜0.01; 1.70 of 150 mM glucose, 1.20 of 10% TLN, 1.10 of 1% TLN, P＜0.05), phosphorylated Drp1 (2.61 of model, 1.44 of HTLN, P＜0.05; 2.80 of 150 mM glucose, 1.50 of 10% TLN, 1.30 of 1% TLN, P＜0.01), and Drp1 located in mitochondria (1.80 of 150 mM glucose, 1.00 of 10% TLN, P＜0.05) were decreased after treatment with TLN. Additionally, TLN improved schwannopathy by increasing MBP (0.50 of model, 1.05 of HTLN, 0.94 of HTLN, P＜0.01; 0.60 of 150 mM glucose, 0.78 of 10% TLN, P＜0.01, 0.72 of 1% TLN, P＜0.05), Sox101 (0.41 of model, 0.99 of LTLN, P＜0.01; 0.48 of 150 mM glucose, 0.65 of 10% TLN, P＜0.05, 0.69 of 1% TLN, P＜0.01), and MPZ (0.48 of model, 0.66 of HTLN, 0.55 of HTLN, P＜0.01; 0.60 of 150 mM glucose, 0.78 of 10% TLN, P＜0.01, 0.75 of 1% TLN, P＜0.05) expressions. In conclusion, our study indicated that TLN’s function on DPN may link to the improvement of the mitochondrial dynamics, which provides scientific evidence for the clinical application.

In vivo effects of TGF-β1 in lung surfactant regulation, lung meachanics amd structure

Pneumologie ◽  
2014 ◽  
Vol 68 (06) ◽  
Author(s):  
E Lopez-Rodriguez ◽  
C Boden ◽  
S Knippenberg ◽  
A Pascual ◽  
J Perez-Gil ◽  
...  
Keyword(s):  
Lung Surfactant ◽  
In Vivo Effects ◽  
Tgf Β1

Evaluation of Sacroiliac Wedge Rotation to Increase Acetabular Ventroversion

1999 ◽  
Vol 12 (04) ◽  
pp. 173-177 ◽  
Author(s):  
R. L. Aper ◽  
M. D. Brown ◽  
M. G. Conzemius
Keyword(s):  
Hip Joint ◽  
Hip Dysplasia ◽  
Clinical Effect ◽  
Pelvic Osteotomy ◽  
Alternative Method ◽  
Angular Measurements ◽  
Si Joint ◽  
In Vivo Effects ◽  
Canine Hip Dysplasia

SummaryTreatment of canine hip dysplasia (CHD) via triple pelvic osteotomy (TPO) is widely accepted as the treatment that best preserves the existing hip joint. TPO, however, has several important disadvantages. In an effort to avoid some of the difficulties associated with TPO an alternative method of creating acetabular ventroversion (AW) was sought. The purpose of this study was to explore the effects of placement of a wedge in the sacroiliac (SI) joint on A W and to compare this to the effect of TPO on A W . On one hemipelvis a 30° pelvic osteotomy plate was used for TPO. The contralateral hemipelvis had a 28° SI wedge inserted into the SI joint. Pre- and postsurgical radiographs of each pelvis were taken and the angular measurements were recorded. On average, the 28° SI wedge resulted in 20.9° of A W, the 30° canine pelvic osteotomy plate resulted in 24.9° A W . Significant differences were not found (p >0.05) between the two techniques. Sacroiliac wedge rotation effectively creates A W and has several theoretical advantages when compared to TPO. The in vivo effects of sacroiliac wedge rotation should be studied in order to evaluate the clinical effect of the technique.Sacroiliac wedge rotation was tested as an alternative method to increase the angle of acetabular ventroversion. This technique effectively rotated the acetabulum and has several theoretical advantages when compared to triple pelvic osteotomy.

Dichloroacetate--its in vivo effects on carbohydrate metabolism in the conscious dog

Diabetes ◽  
1980 ◽  
Vol 29 (9) ◽  
pp. 702-709 ◽  
Author(s):  
M. P. Diamond ◽  
R. C. Rollings ◽  
L. Erlendson ◽  
P. E. Williams ◽  
W. W. Lacy ◽  
...  
Keyword(s):  
Carbohydrate Metabolism ◽  
Conscious Dog ◽  
In Vivo Effects
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