High expressions of the cytoglobin and PGC-1α genes during the tissue regeneration of house gecko (Hemidactylus platyurus) tails

Abstract Background The tissue regeneration process requires high oxygen and energy levels. Cytoglobin (Cygb) is a member of the globin family, which has the ability to bind oxygen, plays a role in dealing with oxidative stress, and carries oxygen into the mitochondria. Energy production for tissue regeneration is associated with mitochondria—especially mitochondrial biogenesis. The peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha protein helps to regulate mitochondrial biogenesis. House geckos ( Hemidactylus platyurus ) are reptiles that have the ability to regenerate the tissue in their tails. House geckos were selected as the animal models for this study in order to analyze the association of Cygb with oxygen supply and the association of PGC-1α with energy production for tissue regeneration. Results The growth of house gecko tails showed a slow growth at the wound healing phase, then followed by a fast growth after wound healing phase of the regeneration process. While Cygb mRNA expression reached its peak at the wound healing phase and slowly decreased until the end of the observation. PGC-1α mRNA was expressed and reached its peak earlier than Cygb. Conclusions The expressions of both the Cygb and PGC-1α genes were relatively high compared to the control group. We therefore suggest that Cygb and PGC-1α play an important role during the tissue regeneration process. Keywords: cytoglobin, PGC-1α, mitochondrial biogenesis, house gecko, tissue regeneration

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High expressions of the cytoglobin and PGC-1α genes during the tissue regeneration of house gecko (Hemidactylus platyurus) tails

10.21203/rs.2.12354/v3 ◽

2020 ◽

Author(s):

Titta Novianti ◽

Vetnizah Juniantito ◽

Ahmad Aulia Jusuf ◽

Evy Ayu Arida ◽

Mohamad Sadikin ◽

...

Keyword(s):

Wound Healing ◽

Tissue Regeneration ◽

Mitochondrial Biogenesis ◽

Energy Production ◽

Energy Levels ◽

Regeneration Process ◽

Control Group ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Healing Phase

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Expression of cytoglobin and PGC-1α is high during tail tissue regeneration of the house gecko (Hemidactylus platyurus)

10.21203/rs.2.12354/v1 ◽

2019 ◽

Author(s):

Titta Novianti ◽

Vetnizah Juniantito ◽

Ahmad Aulia Jusuf ◽

Evy Ayu Arida ◽

Mohamad Sadikin ◽

...

Keyword(s):

Tissue Regeneration ◽

Mitochondrial Biogenesis ◽

Energy Production ◽

Regeneration Process ◽

Peroxisome Proliferator ◽

Oxygen Binding ◽

Binding Ability ◽

Peroxisome Proliferator Activated Receptor ◽

Lower Expression

Abstract Abstract Background Tissue regeneration is a process that need a high demand of oxygen and energy supply. Cytoglobin (Cygb) is a hexacoordinate globin superfamily that possesses strong oxygen-binding ability. Cygb also has a role in preventing cells from oxidative stress and carrying oxygen into the mitochondria. The production of energy for regeneration is associated with mitochondria, especially mitochondrial biogenesis. The peroxisome proliferator-activated receptor gamma coactivator (PGC-1α) is aprotein that plays an important role in regulating mitochondrial biogenesis. The house gecko (Hemidactylus platyurus) is a reptile with high ability for tissue regeneration in its tail. The house gecko was selected as the animal model for this research to analyse the role of Cygb which is associated with oxygen supply and PGC-1α that is related to energy production in tissue regeneration. Results The curve for the tail growth showed three different phases. Cygb mRNA was highly expressed during tissue regeneration. PGC-1α mRNA was expressed earlier than Cygb, with a lower expression but still higher than the control. Conclusions During the tail tissue regeneration process of the house gecko, the expression of Cygb and PGC-1α were dynamic and relatively higher than their expression observed in the control. Cygb and PGC-1α were suspected to have a significant role in the tissue regeneration process.

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Heat-Killed Bifidobacterium breve B-3 Enhances Muscle Functions: Possible Involvement of Increases in Muscle Mass and Mitochondrial Biogenesis

Nutrients ◽

10.3390/nu12010219 ◽

2020 ◽

Vol 12 (1) ◽

pp. 219

Author(s):

Kazuya Toda ◽

Yuki Yamauchi ◽

Azusa Tanaka ◽

Tetsuya Kuhara ◽

Toshitaka Odamaki ◽

...

Keyword(s):

Muscle Mass ◽

Mitochondrial Biogenesis ◽

Muscle Metabolism ◽

Control Group ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Bifidobacterium Breve ◽

Metabolic Functions ◽

Group B ◽

Amp Activated Protein Kinase

A previous clinical study on pre-obesity subjects revealed that Bifidobacterium breve B-3 shows anti-obesity effects and possibly increases muscle mass. Here, we investigated the effects of B-3 on muscle function, such as muscle strength and metabolism, and some signaling pathways in skeletal muscle. Male rodents were orally administered live B-3 (B-3L) or heat-killed B-3 (B-3HK) for 4 weeks. We found that administration of B-3 to rats tended to increase muscle mass and affect muscle metabolism, with stronger effects in the B-3HK group than in the B-3L group. B-3HK significantly increased muscle mass and activated Akt in the rat soleus. With regard to muscle metabolism, B-3HK significantly increased phosphorylated AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α and cytochrome c oxidase (CCO) gene expression in the rat soleus, suggesting an effect on the AMPK-PGC1α-mitochondrial biogenesis pathway. Furthermore, B-3HK promoted oxidative muscle fiber composition in the gastrocnemius. We also observed a significantly higher level of murine grip strength in the B-3HK group than in the control group. These findings suggest the potential of heat-killed B-3 in promoting muscle hypertrophy and modifying metabolic functions, possibly through the Akt and AMPK pathways, respectively.

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Muscle immobilization and remobilization downregulates PGC-1α signaling and the mitochondrial biogenesis pathway

Journal of Applied Physiology ◽

10.1152/japplphysiol.01354.2012 ◽

2013 ◽

Vol 115 (11) ◽

pp. 1618-1625 ◽

Cited By ~ 40

Author(s):

Chounghun Kang ◽

Li Li Ji

Keyword(s):

Oxidative Stress ◽

Cytochrome C ◽

Muscle Atrophy ◽

Mitochondrial Biogenesis ◽

Skeletal Muscle Atrophy ◽

Control Group ◽

Ros Generation ◽

Peroxisome Proliferator ◽

Protein Loss ◽

Peroxisome Proliferator Activated Receptor

Prolonged immobilization (IM) results in skeletal muscle atrophy accompanied by increased reactive oxygen species (ROS) generation, inflammation, and protein degradation. However, the biological consequence of remobilizing such muscle has been studied only sparsely. In this study, we examined the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α)-controlled mitochondrial biogenesis pathway and inflammatory response in mice subjected to 2 wk of hindlimb IM followed by 5 days of remobilization (RM). We hypothesized that ROS generation and activation of redox-sensitive signaling pathways play important roles in the etiology of muscle injury. FVB/N mice (age 2 mo) were randomly assigned to either 14 days of IM by casting one of the hindlimbs ( n = 7), IM followed by 5 days of RM with casting removed ( n = 7), or to a control group (Con; n = 7). Muscle to body weight ratios of three major leg muscles were significantly decreased as a result of IM. Two ubiquitin-proteasome pathway enzymes, muscle atrophy F-box (MAFb or atrogin-1) and muscle ring finger-1 (MuRF-1), were upregulated with IM and maintained at high levels during RM. Protein contents of PGC-1α and nuclear respiratory factors 1 and 2 in tibialis anterior (TA) muscle were reduced by 50% ( P < 0.01) in IM vs. Con, with no recovery observed during RM. IM suppressed mitochondrial transcription factor A and cytochrome- c content by 57% and 63% ( P < 0.01), respectively, and cytochrome- c oxidase activity by 58% ( P < 0.05). Furthermore, mitochondrial DNA content was reduced by 71% ( P < 0.01) with IM. None of these changes were reversed after RM. With RM, TA muscle showed a 2.3-fold ( P < 0.05) higher H2O2 content and a 4-fold ( P < 0.01) higher 8-isoprostane content compared with Con, indicating oxidative stress. Tumor necrosis factor-α and interleukin-6 levels in TA muscle were 4- and 3-fold higher ( P < 0.05), respectively, in IM and RM vs. CON. The nuclear factor-κB (NF-κB) pathway activation was observed only after RM, but not after IM alone. These data indicate an increase in ROS generation during the initial phase of muscle RM that could activate the NF-κB pathway, and elicit inflammation and oxidative stress. These events may hinder muscle recovery from IM-induced mitochondrial deterioration and protein loss.

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Histology Analysis of Tissue Regeneration Process of Digit Tip Mice (Mus musculus) post amputation

Indonesian Journal of Biotechnology and Biodiversity ◽

10.47007/ijobb.v4i2.70 ◽

2020 ◽

Vol 4 (2) ◽

pp. 112-117

Author(s):

Titta Novianti ◽

Febriana Dwi Wahyuni ◽

It Jamilah ◽

Syafruddin Ilyas

Keyword(s):

Wound Healing ◽

Blood Vessel ◽

Tissue Regeneration ◽

Mus Musculus ◽

Histological Analysis ◽

Granule Cells ◽

Regeneration Process ◽

Maturation Phase ◽

Healing Phase ◽

Regeneration Phase

The ability to regenerate tissue is different for each organism. Mice (Mus musculus) able to regenerate the 3rd phalange of a digit. The tissue regeneration process has four phases are the wound-healing phase, the blastema phase, the regeneration phase, and the maturation phase. Each phase has a different process and different activity of cells. Histological analysis is very important to see the activity of each cell in each phase of tissue regeneration. Through histological analysis we can find out the role of each cell in the tissue regeneration process as well as the processes that occur in tissue regeneration. In this study, we analyzed tissue histology in the digit tip mice at each regeneration phase post amputated. The phalanges were amputated on the 3rd phalanges of digit tip of 24 male mice which had been previously sedated using ketamine / xylazine. Digit tip were allowed to grow and regenerate, and samples were taken on days 0, 1, 3, 5, 10, 15, 25 after amputation. Histological analysis was performed using Hematoxylin-eosin staining on a sample preparation that had been made into paraffin blocks first. The histological showed that at the beginning of the wound, the tissue rapidly forms a thin epidermal layer to cover the wound. In the wound healing phase, some of embryonal cells proliferated and migrated actively. In the blastema phase, granule cells cluster to form various new tissues. In the regeneration phase, new tissue begins to form, such as blood vessel, muscle, bone, and epidermal tissue. In the regeneration phase on day 15, several new tissues have begun to form, such as blood vessel tissue, muscle, hemorrhoid, bone and epidermis. Finally, in the maturation phase on day 25, the tissue morphology process occurs and perfecting the digit tip mice tissue.

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Hypoxic Exposure Increases Energy Expenditure by Increasing Carbohydrate Oxidation in Mice

BioMed Research International ◽

10.1155/2020/6159407 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Yeram Park ◽

Deunsol Hwang ◽

Hun-Young Park ◽

Jisu Kim ◽

Kiwon Lim

Keyword(s):

Glucose Metabolism ◽

Energy Expenditure ◽

Pyruvate Dehydrogenase ◽

Hypoxic Condition ◽

Open Circuit ◽

Pyruvate Dehydrogenase Kinase ◽

Hypoxic Exposure ◽

Control Group ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor

Aims. Hypoxic exposure improves glucose metabolism. We investigated to validate the hypothesis that carbohydrate (CHO) oxidation could increase in mice exposed to severe hypoxic conditions. Methods. Seven-week-old male ICR mice (n=16) were randomly divided into two groups: the control group (CON) was kept in normoxic condition (fraction of inspired O2=21%) and the hypoxia group (HYP) was exposed to hypoxic condition (fraction of inspired O2=12%, ≈altitude of 4,300 m). The CON group was pair-fed with the HYP group. After 3 weeks of hypoxic exposure, we measured respiratory metabolism (energy expenditure and substrate utilization) at normoxic conditions for 24 hours using an open-circuit calorimetry system. In addition, we investigated changes in carbohydrate mechanism-related protein expression, including hexokinase 2 (HK2), pyruvate dehydrogenase (PDH), pyruvate dehydrogenase kinase 4 (PDK4), and regulator of the genes involved in energy metabolism (peroxisome proliferator-activated receptor gamma coactivator 1-alpha, PGC1α) in soleus muscle. Results. Energy expenditure (EE) and CHO oxidation over 24 hours were higher in the HYP group by approximately 15% and 34% (p<0.001), respectively. Fat oxidation was approximately 29% lower in the HYP group than the CON group (p<0.01). Body weight gains were significantly lower in the HYP group than in the CON group (CON vs. HYP; 1.9±0.9 vs. −0.3±0.9; p<0.001). Hypoxic exposure for 3 weeks significantly reduced body fat by approximately 42% (p<0.001). PDH and PGC1α protein levels were significantly higher in the HYP group (p<0.05). Additionally, HK2 was approximately 21% higher in the HYP group. Conclusions. Hypoxic exposure might significantly enhance CHO oxidation by increasing the expression of PDH and HK2. This investigation can be useful for patients with impaired glucose metabolism, such as those with type 2 diabetes.

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PPAR-gamma induced AKT3 expression increases levels of mitochondrial biogenesis driving prostate cancer

Oncogene ◽

10.1038/s41388-021-01707-7 ◽

2021 ◽

Vol 40 (13) ◽

pp. 2355-2366

Author(s):

Laura C. A. Galbraith ◽

Ernest Mui ◽

Colin Nixon ◽

Ann Hedley ◽

David Strachan ◽

...

Keyword(s):

Prostate Cancer ◽

Mitochondrial Biogenesis ◽

Nuclear Export ◽

Epithelial To Mesenchymal Transition ◽

Ppar Gamma ◽

Peroxisome Proliferator ◽

Serine Threonine Kinase ◽

Peroxisome Proliferator Activated Receptor ◽

Mesenchymal Transition ◽

And Function

AbstractPeroxisome Proliferator-Activated Receptor Gamma (PPARG) is one of the three members of the PPAR family of transcription factors. Besides its roles in adipocyte differentiation and lipid metabolism, we recently demonstrated an association between PPARG and metastasis in prostate cancer. In this study a functional effect of PPARG on AKT serine/threonine kinase 3 (AKT3), which ultimately results in a more aggressive disease phenotype was identified. AKT3 has previously been shown to regulate PPARG co-activator 1 alpha (PGC1α) localisation and function through its action on chromosome maintenance region 1 (CRM1). AKT3 promotes PGC1α localisation to the nucleus through its inhibitory effects on CRM1, a known nuclear export protein. Collectively our results demonstrate how PPARG over-expression drives an increase in AKT3 levels, which in turn has the downstream effect of increasing PGC1α localisation within the nucleus, driving mitochondrial biogenesis. Furthermore, this increase in mitochondrial mass provides higher energetic output in the form of elevated ATP levels which may fuel the progression of the tumour cell through epithelial to mesenchymal transition (EMT) and ultimately metastasis.

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The Protective Mechanism of SIRT1 in the Regulation of Mitochondrial Biogenesis and Mitochondrial Autophagy in Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-210132 ◽

2021 ◽

pp. 1-9

Author(s):

Fan Ye ◽

Anshi Wu

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mitochondrial Biogenesis ◽

Stress Responses ◽

Histone Deacetylases ◽

Neuronal Morphology ◽

Protective Mechanism ◽

Peroxisome Proliferator ◽

Class Iii ◽

Peroxisome Proliferator Activated Receptor

Silent information-regulated transcription factor 1 (SIRT1) is the most prominent and widely studied member of the sirtuins (a family of mammalian class III histone deacetylases). It is a nuclear protein, and the deacetylation of the peroxisome proliferator-activated receptor coactivator-1 has been extensively implicated in metabolic control and mitochondrial biogenesis and is the basis for studies into its involvement in caloric restriction and its effects on lifespan. The present study discusses the potentially protective mechanism of SIRT1 in the regulation of the mitochondrial biogenesis and autophagy involved in the modulation of Alzheimer’s disease, which may be correlated with the role of SIRT1 in affecting neuronal morphology, learning, and memory during development; regulating metabolism; counteracting stress responses; and maintaining genomic stability. Drugs that activate SIRT1 may offer a promising approach to treating Alzheimer’s disease

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Progressive Reduction in Mitochondrial Mass Is Triggered by Alterations in Mitochondrial Biogenesis and Dynamics in Chronic Kidney Disease Induced by 5/6 Nephrectomy

Biology ◽

10.3390/biology10050349 ◽

2021 ◽

Vol 10 (5) ◽

pp. 349

Author(s):

Rodrigo Prieto-Carrasco ◽

Fernando E. García-Arroyo ◽

Omar Emiliano Aparicio-Trejo ◽

Pedro Rojas-Morales ◽

Juan Carlos León-Contreras ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Mitochondrial Biogenesis ◽

Renal Mass ◽

Renal Damage ◽

Peroxisome Proliferator ◽

Progressive Reduction ◽

Ckd Progression ◽

Peroxisome Proliferator Activated Receptor ◽

Mitochondrial Mass ◽

Mitochondrial Impairment

The five-sixth nephrectomy (5/6Nx) model is widely used to study the mechanisms involved in chronic kidney disease (CKD) progression. Mitochondrial impairment is a critical mechanism that favors CKD progression. However, until now, there are no temporal studies of the change in mitochondrial biogenesis and dynamics that allow determining the role of these processes in mitochondrial impairment and renal damage progression in the 5/6Nx model. In this work, we determined the changes in mitochondrial biogenesis and dynamics markers in remnant renal mass from days 2 to 28 after 5/6Nx. Our results show a progressive reduction in mitochondrial biogenesis triggered by reducing two principal regulators of mitochondrial protein expression, the peroxisome proliferator-activated receptor-gamma coactivator 1-alpha and the peroxisome proliferator-activated receptor alpha. Furthermore, the reduction in mitochondrial biogenesis proteins strongly correlates with the increase in renal damage markers. Additionally, we found a slow and gradual change in mitochondrial dynamics from fusion to fission, favoring mitochondrial fragmentation at later stages after 5/6Nx. Together, our results suggest that 5/6Nx induces the progressive reduction in mitochondrial mass over time via the decrease in mitochondrial biogenesis factors and a slow shift from mitochondrial fission to fusion; both mechanisms favor CKD progression in the remnant renal mass.

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Abdominal Fat SIRT6 Expression and Its Relationship with Inflammatory and Metabolic Pathways in Pre-Diabetic Overweight Patients

International Journal of Molecular Sciences ◽

10.3390/ijms20051153 ◽

2019 ◽

Vol 20 (5) ◽

pp. 1153 ◽

Cited By ~ 11

Author(s):

Nunzia D’Onofrio ◽

Gorizio Pieretti ◽

Feliciano Ciccarelli ◽

Antonio Gambardella ◽

Nicola Passariello ◽

...

Keyword(s):

Regulatory Element ◽

Abdominal Fat ◽

Control Group ◽

Diabetic Patients ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Metformin Therapy ◽

Ppar Γ ◽

Visceral Abdominal Fat ◽

Factor Α

: The role of sirtuin 6 (SIRT6) in adipose abdominal tissue of pre-diabetic (pre-DM) patients is poorly known. Here, we evaluated SIRT6 expression in visceral abdominal fat of obese pre-diabetic patients and the potential effects of metformin therapy. Results indicated that obese pre-DM subjects showed low SIRT6 protein expression and high expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), peroxisome proliferator-activated receptor gamma (PPAR-γ), and sterol regulatory element-binding transcription factor 1 (SREBP-1). Obese pre-DM patients showed high values of glucose, insulin resistance (HOMA-IR), C reactive protein (CRP), nitrotyrosine, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), and low values of insulin (p < 0.05). Of note, abdominal fat tissue of obese pre-DM patients treated with metformin therapy presented higher SIRT6 expression and lower NF-κB, PPAR-γ, and SREBP-1 expression levels compared to pre-DM control group. Collectively, results show that SIRT6 is involved in the inflammatory pathway of subcutaneous abdominal fat of obese pre-DM patients and its expression responds to metformin therapy.

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