Sequential clinical manipulations of embryos results in alterations in expression of genes involved in innate immunity, apoptosis, and mitochondrial function

Skeletal muscle metabolism is highly dependent on mitochondrial function, with impaired mitochondrial biogenesis associated with the development of metabolic diseases such as insulin resistance and type 2 diabetes. Mitochondria display substantial plasticity in skeletal muscle, and are highly sensitive to levels of physical activity. It is thought that physical activity promotes mitochondrial biogenesis in skeletal muscle through increased expression of genes encoded in both the nuclear and the mitochondrial genome; however, how this process is co-ordinated at the cellular level is poorly understood. Nuclear receptors (NRs) are key signalling proteins capable of integrating environmental factors and mitochondrial function, thereby providing a potential link between exercise and mitochondrial biogenesis. The aim of this review is to highlight the function of NRs in skeletal muscle mitochondrial biogenesis and discuss the therapeutic potential of NRs for the management and treatment of chronic metabolic disease.

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Association between hepatic steatosis and hepatic expression of genes involved in innate immunity in patients with chronic hepatitis C

Cytokine ◽

10.1016/j.cyto.2013.04.012 ◽

2013 ◽

Vol 63 (2) ◽

pp. 145-150 ◽

Cited By ~ 2

Author(s):

Hidenori Toyoda ◽

Takashi Kumada ◽

Seiki Kiriyama ◽

Makoto Tanikawa ◽

Yasuhiro Hisanaga ◽

...

Keyword(s):

Innate Immunity ◽

Chronic Hepatitis ◽

Hepatitis C ◽

Hepatic Steatosis ◽

Chronic Hepatitis C ◽

Hepatic Expression ◽

Expression Of Genes

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Adipose Tissue Resting Energy Expenditure and Expression of Genes Involved in Mitochondrial Function Are Higher in Women than in Men

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2012-2764 ◽

2013 ◽

Vol 98 (2) ◽

pp. E370-E378 ◽

Cited By ~ 51

Author(s):

Intawat Nookaew ◽

Per-Arne Svensson ◽

Peter Jacobson ◽

Margareta Jernås ◽

Magdalena Taube ◽

...

Keyword(s):

Adipose Tissue ◽

Energy Expenditure ◽

Mitochondrial Function ◽

Resting Energy Expenditure ◽

Expression Of Genes ◽

Resting Energy

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Rooibos Flavonoids, Aspalathin, Isoorientin, and Orientin Ameliorate Antimycin A-Induced Mitochondrial Dysfunction by Improving Mitochondrial Bioenergetics in Cultured Skeletal Muscle Cells

Molecules ◽

10.3390/molecules26206289 ◽

2021 ◽

Vol 26 (20) ◽

pp. 6289

Author(s):

Sinenhlanhla X. H. Mthembu ◽

Christo J. F. Muller ◽

Phiwayinkosi V. Dludla ◽

Evelyn Madoroba ◽

Abidemi P. Kappo ◽

...

Keyword(s):

Mitochondrial Dysfunction ◽

Mitochondrial Function ◽

C2c12 Myotubes ◽

Antimycin A ◽

Mrna Levels ◽

Expression Of Genes ◽

Rooibos Tea ◽

The Impact ◽

Dietary Flavonoids

The current study investigated the physiological effects of flavonoids found in daily consumed rooibos tea, aspalathin, isoorientin, and orientin on improving processes involved in mitochondrial function in C2C12 myotubes. To achieve this, C2C12 myotubes were exposed to a mitochondrial channel blocker, antimycin A (6.25 µM), for 12 h to induce mitochondrial dysfunction. Thereafter, cells were treated with aspalathin, isoorientin, and orientin (10 µM) for 4 h, while metformin (1 µM) and insulin (1 µM) were used as comparators. Relevant bioassays and real-time PCR were conducted to assess the impact of treatment compounds on some markers of mitochondrial function. Our results showed that antimycin A induced alterations in the mitochondrial respiration process and mRNA levels of genes involved in energy production. In fact, aspalathin, isoorientin, and orientin reversed such effects leading to the reduced production of intracellular reactive oxygen species. These flavonoids further enhanced the expression of genes involved in mitochondrial function, such as Ucp 2, Complex 1/3, Sirt 1, Nrf 1, and Tfam. Overall, the current study showed that dietary flavonoids, aspalathin, isoorientin, and orientin, have the potential to be as effective as established pharmacological drugs such as metformin and insulin in protecting against mitochondrial dysfunction in a preclinical setting; however, such information should be confirmed in well-established in vivo disease models.

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Aberrant mitochondrial function in patient-derived neural cells from CDKL5 deficiency disorder and Rett syndrome

Human Molecular Genetics ◽

10.1093/hmg/ddz208 ◽

2019 ◽

Vol 28 (21) ◽

pp. 3625-3636

Author(s):

Smita Jagtap ◽

Jessica M Thanos ◽

Ting Fu ◽

Jennifer Wang ◽

Jasmin Lalonde ◽

...

Keyword(s):

Oxygen Consumption ◽

Rett Syndrome ◽

Mitochondrial Function ◽

Progenitor Cell ◽

Neural Progenitor Cell ◽

Neural Cells ◽

Wild Type ◽

Expression Of Genes ◽

Mutant Lines ◽

Differential Expression Of Genes

Abstract The X-linked neurodevelopmental diseases CDKL5 deficiency disorder (CDD) and Rett syndrome (RTT) are associated with intellectual disability, infantile spasms and seizures. Although mitochondrial dysfunction has been suggested in RTT, less is understood about mitochondrial function in CDD. A comparison of bioenergetics and mitochondrial function between isogenic wild-type and mutant neural progenitor cell (NPC) lines revealed increased oxygen consumption in CDD mutant lines, which is associated with altered mitochondrial function and structure. Transcriptomic analysis revealed differential expression of genes related to mitochondrial and REDOX function in NPCs expressing the mutant CDKL5. Furthermore, a similar increase in oxygen consumption specific to RTT patient–derived isogenic mutant NPCs was observed, though the pattern of mitochondrial functional alterations was distinct from CDKL5 mutant–expressing NPCs. We propose that aberrant neural bioenergetics is a common feature between CDD and RTT disorders. The observed changes in oxidative stress and mitochondrial function may facilitate the development of therapeutic agents for CDD and related disorders.

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The Impact of Diet on Expression of Genes Involved in Innate Immunity in Goat Blood

Journal of Agricultural Science ◽

10.5539/jas.v8n3p1 ◽

2016 ◽

Vol 8 (3) ◽

pp. 1 ◽

Cited By ~ 3

Author(s):

Mulumebet Worku ◽

Ahmed Abdalla ◽

Sarah Adjei-Fremah ◽

Hamid Ismail

Keyword(s):

Gene Expression ◽

Innate Immunity ◽

Inflammatory Cytokines ◽

Control Group ◽

Colony Stimulating Factor ◽

Sericea Lespedeza ◽

Expression Of Genes ◽

The Impact ◽

Stimulating Factor ◽

Pro Inflammatory Cytokines

Sericea Lespedeza (SL), is a high-quality, low input forage that suppresses gastro-intestinal parasites in goats. The effect of dietary SL on the expression of genes involved in innate immunity in goats has not been established. The objective of this study was to evaluate the impact of a diet containing SL on the expression of genes involved in innate immunity in goat blood. Blood was collected by jugular venipuncture from goats fed a diet of 75% SL (n = 9) and a control group (n = 7), fed a SL free diet. Blood was used to evaluate expression of (CD-14, TLR-2, TLR-4, IL-10, IL-8, IL-2, INF-r, and TNF-a). Serum was extracted and used for evaluation of the secretion of pro-inflammatory cytokines (TNF-a, IFNr, granulocyte colony stimulating factor (GCSF), granulocyte-macrophage colony-stimulating factor (GMCSF), IL-1a, IL-8, IP-10 and RANTES) using a commercial ELISA kit. The level of gene expression of CD-14, TLR-2, TLR-4, IL-10, IL-8, IL-2, INF-r, and TNF-a was higher in treated animals compared to control. The Sericea Lespedeza diet affected the secretion of pro-inflammatory cytokines by increasing the serum levels of TNF-a, IFNr, GCSF, GMCSF, IL-1a, IP-10 (P < 0.0002), and by decreasing (P < 0.0001) IL-8 and RANTES in blood from goats fed SL. This suggests that dietary tannins modulate gene expression and may affect the goat's innate immune response in blood. Further research is needed to understand and harness the effect of dietary condensed tannins to modulate innate immunity in goats.

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Coronavirus infection and PARP expression dysregulate the NAD metabolome: An actionable component of innate immunity

Journal of Biological Chemistry ◽

10.1074/jbc.ra120.015138 ◽

2020 ◽

Vol 295 (52) ◽

pp. 17986-17996 ◽

Cited By ~ 1

Author(s):

Collin D. Heer ◽

Daniel J. Sanderson ◽

Lynden S. Voth ◽

Yousef M. O. Alhammad ◽

Mark S. Schmidt ◽

...

Keyword(s):

Innate Immunity ◽

Hepatitis Virus ◽

Murine Hepatitis Virus ◽

Nicotinamide Riboside ◽

Antiviral Responses ◽

Expression Of Genes ◽

Nad Synthesis ◽

Genes Encoding ◽

Antiviral Activities ◽

A Chain

Poly(ADP-ribose) polymerase (PARP) superfamily members covalently link either a single ADP-ribose (ADPR) or a chain of ADPR units to proteins using NAD as the source of ADPR. Although the well-known poly(ADP-ribosylating) (PARylating) PARPs primarily function in the DNA damage response, many noncanonical mono(ADP-ribosylating) (MARylating) PARPs are associated with cellular antiviral responses. We recently demonstrated robust up-regulation of several PARPs following infection with murine hepatitis virus (MHV), a model coronavirus. Here we show that SARS-CoV-2 infection strikingly up-regulates MARylating PARPs and induces the expression of genes encoding enzymes for salvage NAD synthesis from nicotinamide (NAM) and nicotinamide riboside (NR), while down-regulating other NAD biosynthetic pathways. We show that overexpression of PARP10 is sufficient to depress cellular NAD and that the activities of the transcriptionally induced enzymes PARP7, PARP10, PARP12 and PARP14 are limited by cellular NAD and can be enhanced by pharmacological activation of NAD synthesis. We further demonstrate that infection with MHV induces a severe attack on host cell NAD+ and NADP+. Finally, we show that NAMPT activation, NAM, and NR dramatically decrease the replication of an MHV that is sensitive to PARP activity. These data suggest that the antiviral activities of noncanonical PARP isozyme activities are limited by the availability of NAD and that nutritional and pharmacological interventions to enhance NAD levels may boost innate immunity to coronaviruses.

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