Cardiopulmonary reflex, cardiac cytokines, and nandrolone decanoate: response to resistance training in rats

2015 ◽  
Vol 93 (11) ◽  
pp. 985-991 ◽  
Author(s):  
Ewelyne Miranda Lima ◽  
Andrews Marques Nascimento ◽  
Girlandia Alexandre Brasil ◽  
Ieda Carneiro Kalil ◽  
Dominik Lenz ◽  
...  

This study evaluated the effects of nandrolone associated with resistance training (RT) on cardiac cytokines, angiotensin-converting enzyme activity (ACEA), and the sensitivity of the Bezold-Jarisch reflex (BJR). Male Wistar rats were divided into 3 groups: CONT (received vehicle, no training); EXERC (RT: after one week of water adaptation, rats were exercised by jumping into water twice a week for 4 weeks), and ND+EXERC (received nandrolone decanoate 10 mg/kg, twice/week, i.m, associated with RT). The BJR was analysed by measuring bradycardic and hypotensive responses elicited by serotonin administration. Myocyte hypertrophy and matrix collagen deposition were determined by morphometric analysis of H&E and picrosirius red-stained samples, respectively. TNF-α and ACEA were also studied. RT promoted physiological myocyte hyrpertrophy but did not cause changes in the other parameters. The association of ND with RT increased myocyte hypertrophy, deposition of matrix type I collagen, TNF-α and ACEA; decreased IL-10, and impairment in the BJR were observed in ND+EXERC compared with CONT and EXERC. ND is associated with alterations in cardiac structure and function as a result of the development of pathological cardiac hypertrophy (cardiac cytokine imbalance, elevation of ACEA) and cardiac injury, even when combined with resistance training.

2008 ◽  
Vol 104 (1) ◽  
pp. 170-177 ◽  
Author(s):  
Tatsuro Hirose ◽  
Koichi Nakazato ◽  
Hongsun Song ◽  
Naokata Ishii

The aim of this study was to examine the effect of hindlimb suspension (HS) on the expressions of COL1A2 (type I collagen α2 chain) mRNA and its regulatory factors, transforming growth factors (TGF)-β1, -β2, and -β3, phosphorylated Smad3, and tumor necrosis factor-α (TNF-α) in rat hindlimb muscles. Forty-eight male Wistar rats (age, 5 wk) were randomly assigned to HS for 1, 3, 7, and 14 days and control ( n = 6 for each). During the exposure to HS, COL1A2 mRNA expression decreased in the soleus muscle at day 3 and recovered to control level at day 7. The content of TNF-α, one of the negative regulatory factors for COL1A2, increased from day 3 until day 14. On the other hand, the contents of TGF-β1, TGF-β3, and Smad3, positive regulatory factors for COL1A2, increased at day 7. The in situ hybridization for COL1A2 and the immunohistochemistry of TGF-β1 and TNF-α revealed their expressions around nerve-related tissues, including muscle spindles and connective tissue sheath. The results indicate that the transcriptional activity of COL1A2 in the soleus muscle initially decreases in response to unloading through an increase in TNF-α production; thereafter, it returns toward normal level through the activated TGF-β/Smad pathway.


2018 ◽  
Vol 69 (7) ◽  
pp. 1706-1709
Author(s):  
Nicoleta Dumitru ◽  
Andra Cocolos ◽  
Andra Caragheorgheopol ◽  
Constantin Dumitrache ◽  
Ovidiu Gabriel Bratu ◽  
...  

There is an increased interest and more studies highlight the fact that bone strength depends not only on bone tissue quantity, but also on its quality, which is characterized by the geometry and shape of bones, trabecular bone microarchitecture, mineral content, organic matrix and bone turnover. Fibrillar type I collagen is the major organic component of bone matrix, providing form and a stable template for mineralization. The biomedical importance of collagen as a biomaterial for medical and cosmetic purposes and the improvement of the molecular, cellular biology and analytical technologies, led to increasing interest in establishing the structure of this protein and in setting of the relationships between sequence, structure, and function. Bone collagen crosslinking chemistry and its molecular packing structure are considered to be distinct features. This unique post-translational modifications provide to the fibrillar collagen matrices properties such as tensile strength and viscoelasticity. Understanding the complex structure of bone type I collagen as well as the dynamic nature of bone tissues will help to manage new therapeutic approaches to bone diseases.


2000 ◽  
Vol 20 (3) ◽  
pp. 912-918 ◽  
Author(s):  
Patricia Greenwel ◽  
Shizuko Tanaka ◽  
Dmitri Penkov ◽  
Wen Zhang ◽  
Michelle Olive ◽  
...  

ABSTRACT Extracellular matrix (ECM) formation and remodeling are critical processes for proper morphogenesis, organogenesis, and tissue repair. The proinflammatory cytokine tumor necrosis factor alpha (TNF-α) inhibits ECM accumulation by stimulating the expression of matrix proteolytic enzymes and by downregulating the deposition of structural macromolecules such as type I collagen. Stimulation of ECM degradation has been linked to prolonged activation of jun gene expression by the cytokine. Here we demonstrate that TNF-α inhibits transcription of the gene coding for the α2 chain of type I collagen [α2(I) collagen] in cultured fibroblasts by stimulating the synthesis and binding of repressive CCAAT/enhancer proteins (C/EBPs) to a previously identified TNF-α-responsive element. This conclusion was based on the concomitant identification of C/EBPβ and C/EBPδ as TNF-α-induced factors by biochemical purification and expression library screening. It was further supported by the ability of the C/EBP-specific dominant-negative (DN) protein to block TNF-α inhibition of α2(I) collagen but not TNF-α stimulation of the MMP-13 protease. The DN protein also blocked TNF-α downregulation of the gene coding for the α1 chain of type I collagen. The study therefore implicates repressive C/EBPs in the TNF-α-induced signaling pathway that controls ECM formation and remodeling.


2013 ◽  
Vol 56 (2) ◽  
pp. 73-79
Author(s):  
Lenka Bittnerová ◽  
Alena Jiroutová ◽  
Emil Rudolf ◽  
Martina Řezáčová ◽  
Jiří Kanta

Activated hepatic stellate cells (HSC) are a major source of fibrous proteins in cirrhotic liver. Inducing or accelerating their apoptosis is a potential way of liver fibrosis treatment. Extracellular matrix (ECM) surrounding cells in tissue affects their differentiation, migration, proliferation and function. Type I collagen is the main ECM component in fibrotic liver. We have examined how this protein modifies apoptosis of normal rat HSC induced by gliotoxin, cycloheximide and cytochalasin D in vitro and spontaneous apoptosis of HSC isolated from CCl4-damaged liver. We have found that type I collagen gel enhances HSC apoptosis regardless of the agent triggering this process.


2019 ◽  
Vol 20 (11) ◽  
pp. 2734 ◽  
Author(s):  
Young Hun Lee ◽  
Eun Kyoung Seo ◽  
Seung-Taek Lee

Skullcapflavone II is a flavonoid derived from the root of Scutellaria baicalensis, a herbal medicine used for anti-inflammatory and anti-cancer therapies. We analyzed the effect of skullcapflavone II on the expression of matrix metalloproteinase-1 (MMP-1) and integrity of type I collagen in foreskin fibroblasts. Skullcapflavone II did not affect the secretion of type I collagen but reduced the secretion of MMP-1 in a dose- and time-dependent manner. Real-time reverse transcription-PCR and reporter gene assays showed that skullcapflavone II reduced MMP-1 expression at the transcriptional level. Skullcapflavone II inhibited the serum-induced activation of the extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways required for MMP-1 transactivation. Skullcapflavone II also reduced tumor necrosis factor (TNF)-α-induced nuclear factor kappa light chain enhancer of activated B cells (NF-κB) activation and subsequent MMP-1 expression. In three-dimensional culture of fibroblasts, skullcapflavone II down-regulated TNF-α-induced MMP-1 secretion and reduced breakdown of type I collagen. These results indicate that skullcapflavone II is a novel biomolecule that down-regulates MMP-1 expression in foreskin fibroblasts and therefore could be useful in therapies for maintaining the integrity of extracellular matrix.


2006 ◽  
Vol 38 (Supplement) ◽  
pp. S281 ◽  
Author(s):  
Luc E. Gosselin ◽  
Kathleen McCormick ◽  
Jacqueline Williams

2013 ◽  
Vol 288 (23) ◽  
pp. 16738-16746 ◽  
Author(s):  
Vittorio Abbonante ◽  
Cristian Gruppi ◽  
Diana Rubel ◽  
Oliver Gross ◽  
Remigio Moratti ◽  
...  

Growing evidence demonstrates that extracellular matrices regulate many aspects of megakaryocyte (MK) development; however, among the different extracellular matrix receptors, integrin α2β1 and glycoprotein VI are the only collagen receptors studied in platelets and MKs. In this study, we demonstrate the expression of the novel collagen receptor discoidin domain receptor 1 (DDR1) by human MKs at both mRNA and protein levels and provide evidence of DDR1 involvement in the regulation of MK motility on type I collagen through a mechanism based on the activity of SHP1 phosphatase and spleen tyrosine kinase (Syk). Specifically, we demonstrated that inhibition of DDR1 binding to type I collagen, preserving the engagement of the other collagen receptors, glycoprotein VI, α2β1, and LAIR-1, determines a decrease in MK migration due to the reduction in SHP1 phosphatase activity and consequent increase in the phosphorylation level of its main substrate Syk. Consistently, inhibition of Syk activity restored MK migration on type I collagen. In conclusion, we report the expression and function of a novel collagen receptor on human MKs, and we point out that an increasing level of complexity is necessary to better understand MK-collagen interactions in the bone marrow environment.


2021 ◽  
Vol 25 (273) ◽  
pp. 97-113
Author(s):  
Max Sander de Oliveira da Mota ◽  
Maria Sara de Lima Coutinho Mattera ◽  
Thaís Verônica Saori Tsosura ◽  
Fernando Yamamoto Chiba ◽  
Renato Felipe Pereira ◽  
...  

The present study, aimed to evaluate the effects of resistance training (RT) on glycemia, insulinemia, insulin sensitivity, insulin signaling (IS), and tumor necrosis factor-α (TNF-α) levels in rats with periodontitis. 40 male Wistar rats were distributed into 4 groups: sedentary control group (SCN), exercised control group (ExCN), sedentary ligature-induced periodontal disease group (SPD), and exercised ligature-induced periodontal disease group (ExPD). 28 days after inducing periodontitis the RT started (14-week). Glycemia, insulin, TNF-α levels, and insulin sensitivity were analyzed using various methods. IS was evaluated by measuring tyrosine phosphorylated pp185 in insulin-sensitive tissues (western blot method). Higher levels of insulin, HOMA-IR, and TNF-α, and a decrease in insulin sensitivity were observed in the SPD group, which also had decreased levels of insulin-stimulated tyrosine phosphorylated pp185 in muscle and adipose tissue, when compared to the other groups. The ExPD group had increased levels of insulin-stimulated tyrosine phosphorylated pp185 compared to the SPD group, but showed no significant difference when compared to the SCN and ExCN groups. RT reversed both the insulin resistance (IR) and the IS alterations in rats with induced periodontitis, and decreased the insulin and TNF-α levels. Therefore, the results of show the importance of RT in preventing or reversing IR in rats with periodontitis.


Author(s):  
RAMANDEEP KAUR ◽  
Makula Ajitha

Objective: In the present study, transdermal nanoemulsion (NE) gel of lovastatin was investigated for its anti-osteoporosis effect on the long bones of rat i.e. tibia. Methods: Male wistar rats (n=30, weighing 180-200g) were taken for this study and grouped as: 1) control (normal saline daily), 2) Dex (dexamethasone sodium; 25 mg/kg subcutaneously twice a week), 3) Dex+LNG5 (lovastatin nanoemulsion gel; 5 mg/kg/d transdermally daily), 4) Dex+LNG10 (lovastatin nanoemulsion gel; 10 mg/kg/d transdermally daily), and 5) Dex+ALN (alendronate sodium; 0.03 mg/kg/d orally daily). All the treatments were carried out for 60 d. At the end of the experiment, all animals were anesthetized using diethyl ether and collected blood samples from retro-orbital venous plexus of rats in dry eppendorf tubes followed by the sacrifice of animals by cervical dislocation method and collected tibia bones of both the legs for analysis. Results: Bone formation biomarkers (OC: osteocalcin, b-ALP: bone-specific alkaline phosphatase, PINP: N-terminal propeptides of type I procollagen) were significantly improved and resorption biomarkers (CTx: C-terminal cross-linking telopeptides of type-I collagen, TRAcP5b: isoform 5b of tartarate resistant acid phosphatase) were significantly reduced in the LNG5 (p<0.05) and LNG10 (p<0.05) treatment groups when compared to Dex. In vivo anti-osteoporotic results demonstrated the formation of new bone in osteoporotic rat tibias. Biomechanical strength testing demonstrated increased load-bearing capacity of rat tibias in the treated animals in comparison with the osteoporotic group (p<0.05 for LNG5 and p<0.01 for LNG10). Conclusion: Thus, the transdermal NE gel formulation of lovastatin demonstrated the greater potential for the treatment of osteoporosis.


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