scholarly journals Protective Effects of Sonic Hedgehog Against Ischemia/Reperfusion Injury in Mouse Skeletal Muscle via AKT/mTOR/p70S6K Signaling

2017 ◽  
Vol 43 (5) ◽  
pp. 1813-1828 ◽  
Author(s):  
Qiu Zeng ◽  
Qining Fu ◽  
Xuehu Wang ◽  
Yu Zhao ◽  
Hong Liu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Sonic Hedgehog ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Systemic Administration ◽  
Skeletal Muscle Regeneration ◽  
Protective Effects ◽  
Shh Signaling ◽  
Apoptosis Pathway

Background/Aims: Skeletal muscle ischemia/reperfusion (I/R) injury is a common and severe disease. Sonic hedgehog (Shh) plays a critical role in post-natal skeletal muscle regeneration. In the present study, the role of Shh in skeletal muscle I/R injury and the mechanisms involved were investigated. Methods: The expression of Shh, AKT/mTOR/p70S6K and apoptosis pathway components were evaluated following tourniquet-induced skeletal muscle I/R injury. Then, mice were subjected to systemic administration of cyclopamine or one-shot treatment of a plasmid encoding the human Shh gene (phShh) to examine the effects of Shh on I/R injury. Moreover, mice were subjected to systemic administration of NVP-BEZ235 to investigate the role of the AKT/mTOR/p70S6K pathway in Shh-triggered skeletal muscle protection. Results: We found that the levels of Shh, AKT/mTOR/p70S6K pathway components and Cleaved Caspase 3 and the Bax/Bcl2 ratio initially increased and then decreased at different time points post-I/R injury. Moreover, Shh protected skeletal muscle against I/R injury by alleviating muscle destruction, reducing interstitial fibrosis and inhibiting apoptosis, and these protective effects were abrogated when the AKT/mTOR/p70S6K pathway was inhibited. Conclusion: Collectively, these data suggest that Shh signaling exerts a protective role through the AKT/mTOR/p70S6K signaling pathway during skeletal muscle I/R injury. Thus, Shh signaling may be a therapeutic target for protecting skeletal muscle from I/R injury.

LncRNA SNHG12 Improves Cerebral Ischemic-reperfusion Injury by Activating SIRT1/FOXO3a Pathway through I nhibition of Autophagy and Oxidative Stress

2020 ◽  
Vol 17 (4) ◽  
pp. 394-401
Author(s):  
Yuanhua Wu ◽  
Yuan Huang ◽  
Jing Cai ◽  
Donglan Zhang ◽  
Shixi Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Cell Activity ◽  
Ht22 Cells ◽  
Cerebral Ischemic ◽  
Cerebral Ischemic Reperfusion ◽  
And Oxidative Stress

Background: Ischemia/reperfusion (I/R) injury involves complex biological processes and molecular mechanisms such as autophagy. Oxidative stress plays a critical role in the pathogenesis of I/R injury. LncRNAs are the regulatory factor of cerebral I/R injury. Methods: This study constructs cerebral I/R model to investigate role of autophagy and oxidative stress in cerebral I/R injury and the underline regulatory mechanism of SIRT1/ FOXO3a pathway. In this study, lncRNA SNHG12 and FOXO3a expression was up-regulated and SIRT1 expression was down-regulated in HT22 cells of I/R model. Results: Overexpression of lncRNA SNHG12 significantly increased the cell viability and inhibited cerebral ischemicreperfusion injury induced by I/Rthrough inhibition of autophagy. In addition, the transfected p-SIRT1 significantly suppressed the release of LDH and SOD compared with cells co-transfected with SIRT1 and FOXO3a group and cells induced by I/R and transfected with p-SNHG12 group and overexpression of cells co-transfected with SIRT1 and FOXO3 further decreased the I/R induced release of ROS and MDA. Conclusion: In conclusion, lncRNA SNHG12 increased cell activity and inhibited oxidative stress through inhibition of SIRT1/FOXO3a signaling-mediated autophagy in HT22 cells of I/R model. This study might provide new potential therapeutic targets for further investigating the mechanisms in cerebral I/R injury and provide.

scholarly journals A critical role of autocrine sonic hedgehog signaling in human CD138+ myeloma cell survival and drug resistance

Blood ◽  
2014 ◽  
Vol 124 (13) ◽  
pp. 2061-2071 ◽  
Author(s):  
Zhiqiang Liu ◽  
Jingda Xu ◽  
Jin He ◽  
Yuhuan Zheng ◽  
Haiyan Li ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Survival ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Critical Role ◽  
Myeloma Cell ◽  
Sonic Hedgehog Signaling ◽  
Key Points

Key Points CD138+ MM cells are a major source of SHH. Autocrine SHH enhances MM drug resistance.

Role of Platelet-Activating Factor in Cardiovascular Pathophysiology

2000 ◽  
Vol 80 (4) ◽  
pp. 1669-1699 ◽  
Author(s):  
Giuseppe Montrucchio ◽  
Giuseppe Alloatti ◽  
Giovanni Camussi
Keyword(s):  
Cardiovascular System ◽  
Cell Biology ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Experimental Studies ◽  
Platelet Activating Factor ◽  
Biologically Active ◽  
Endothelial Cell Migration

Platelet-activating factor (PAF) is a phospholipid mediator that belongs to a family of biologically active, structurally related alkyl phosphoglycerides. PAF acts via a specific receptor that is coupled with a G protein, which activates a phosphatidylinositol-specific phospholipase C. In this review we focus on the aspects that are more relevant for the cell biology of the cardiovascular system. The in vitro studies provided evidence for a role of PAF both as intercellular and intracellular messenger involved in cell-to-cell communication. In the cardiovascular system, PAF may have a role in embryogenesis because it stimulates endothelial cell migration and angiogenesis and may affect cardiac function because it exhibits mechanical and electrophysiological actions on cardiomyocytes. Moreover, PAF may contribute to modulation of blood pressure mainly by affecting the renal vascular circulation. In pathological conditions, PAF has been involved in the hypotension and cardiac dysfunctions occurring in various cardiovascular stress situations such as cardiac anaphylaxis and hemorrhagic, traumatic, and septic shock syndromes. In addition, experimental studies indicate that PAF has a critical role in the development of myocardial ischemia-reperfusion injury. Indeed, PAF cooperates in the recruitment of leukocytes in inflamed tissue by promoting adhesion to the endothelium and extravascular transmigration of leukocytes. The finding that human heart can produce PAF, expresses PAF receptor, and is sensitive to the negative inotropic action of PAF suggests that this mediator may have a role also in human cardiovascular pathophysiology.

Itraconazole Attenuates Peritoneal Fibrosis Through Its Effect on the Sonic Hedgehog Signaling Pathway in Mice

2018 ◽  
Vol 48 (6) ◽  
pp. 456-464 ◽  
Author(s):  
Jin Sug Kim ◽  
Kyung Sook Cho ◽  
Seon Hwa Park ◽  
Sang Ho Lee ◽  
Ji Hwan Lee ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Sonic Hedgehog ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Isotonic Saline ◽  
Control Group ◽  
Protective Effects ◽  
Peritoneal Fibrosis ◽  
Shh Signaling ◽  
Itraconazole Treatment

Background: Peritoneal fibrosis is a devastating complication of peritoneal dialysis. However, its precise mechanism is unclear, and specific treatments have not yet been established. Recent evidence suggests that the sonic hedgehog (SHH) signaling pathway is involved in tissue fibrogenesis. Drugs that inhibit this pathway are emerging in the field of anti-fibrosis therapy. Itraconazole, an anti-fungal agent, was also recently recognized as an inhibitor of the SHH signaling pathway. In this study, we used a mouse model to investigate whether the SHH signaling pathway is involved in the development of peritoneal fibrosis and the effects of itraconazole on peritoneal fibrosis. Methods: Peritoneal fibrosis was induced by intraperitoneal (IP) injection of 0.1% chlorhexidine gluconate (CG) solution every other day for 4 weeks, with or without itraconazole treatment (20 mg/kg, IP injection on a daily basis). Male C57BL/6 mice were divided into 4 groups: saline group, saline plus itraconazole group, CG group, and CG plus itraconazole group. Isotonic saline was administered intraperitoneally to the control group. The peritoneal tissues were evaluated for histological changes, expression of fibrosis markers, and the main components of the SHH signaling pathway. Results: Peritoneal thickening was evident in the CG group and was significantly decreased by itraconazole administration (80.4 ± 7.7 vs. 28.2 ± 3.8 µm, p < 0.001). The expression of the following SHH signaling pathway components was upregulated in the CG group and suppressed by itraconazole treatment: SHH, patched, smoothened, and glioma-associated oncogene transcription factor 1. The IP injection of CG solution increased the expression of fibrosis markers such as α-smooth muscle actin and transforming growth factor-β1 in the peritoneal tissues. Itraconazole treatment significantly decreased the expression of these markers. Conclusion: Our study provides the first evidence that the SHH signaling pathway may be implicated in peritoneal fibrosis. It also demonstrates that itraconazole treatment has protective effects on peritoneal fibrosis through the regulation of the SHH signaling pathway. These findings suggest that blockage of the SHH signaling pathway is a potential therapeutic strategy for peritoneal fibrosis.

scholarly journals The Role of Metabolic Remodeling in Macrophage Polarization and Its Effect on Skeletal Muscle Regeneration

2019 ◽  
Vol 30 (12) ◽  
pp. 1553-1598 ◽  
Author(s):  
Francesca De Santa ◽  
Laura Vitiello ◽  
Alessio Torcinaro ◽  
Elisabetta Ferraro
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Macrophage Polarization ◽  
Skeletal Muscle Regeneration ◽  
Metabolic Remodeling

The Potential Role of Insulin-Like Growth Factors in Skeletal Muscle Regeneration

1996 ◽  
Vol 21 (4) ◽  
pp. 236-250 ◽  
Author(s):  
Jamie MacGregor ◽  
Wade S. Parkhouse
Keyword(s):  
Skeletal Muscle ◽  
Growth Hormone ◽  
Growth Factors ◽  
Muscle Regeneration ◽  
Potential Role ◽  
Tissue Growth ◽  
Skeletal Muscle Regeneration ◽  
Tissue Type ◽  
Insulin Like Growth Factors

The role of the insulin-like growth factors I and II (IGF-I and IGF-II), previously known as the somatomedins, in general growth and development of various tissues has been known for many years. Thought of exclusively as endocrine factors produced by the liver, and under the control of growth hormone, the somatomedins were known as the intermediaries by which growth hormone exerted its cellular effects during tissue growth and maturation. Eventually it was discovered that virtually every tissue type is capable of autocrine production of the IGFs, and their involvement in skeletal muscle tissue repair and regeneration became apparent. Recent advances in technology have allowed the characterisation of many of the different growth factors believed to play a role in muscle regeneration, and experimental manipulations of cells in culture have provided insight into the effects of the various growth factors on the myoblast. This paper explores the potential role of the IGFs in skeletal muscle regeneration. A critical role of IGF-II in terminal differentiation of proliferating muscle precurser cells following injury is proposed. Key words: growth factors, myogenesis, skeletal muscle regeneration

Abstract 2894: Essential Role of ERK 1/2 in Sildenafil-Induced Early and Delayed Cardioprotection in Mice

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Anindita das ◽  
Lei Xi ◽  
Fadi N Salloum ◽  
Yuan J Rao ◽  
Rakesh C Kukreja
Keyword(s):  
South Carolina ◽  
Infarct Size ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Heart Association ◽  
Myocardial Infarct Size ◽  
Western Blots ◽  
Delayed Cardioprotection

Background: Sildenafil (SIL), a potent inhibitor of phosphodiesterase-5 induces powerful protection against myocardial ischemia-reperfusion (I-R) injury through activation of protein kinase G (PKG). However, the downstream targets of PKG in SIL-induced cardioprotection remain unclear. We hypothesized that PKG-dependent activation of survival kinase, ERK may play a critical role in SIL-induced cardioprotection in mice. Methods & Results: Ventricular myocytes were isolated from adult male ICR mice and exposed to 40 min of simulated ischemia (SI) with/without 1 hr pre-incubation of SIL (1 μM). Myocyte necrosis and apoptosis were determined after 1 hr or 18 hrs of reoxygenation (RO) using trypan blue or TUNEL assay, respectively. Pretreatment with SIL protected cardiomyocytes after SI-RO (necrosis 18.5±0.5% and apoptosis 6.6±0.7%; n=4, p<0.001) as compared with controls (necrosis 42.1±1.8% and apoptosis 23.3±0.9%). Co-incubation of PD98059 (20 μM), a selective ERK1/2 inhibitor blocked both anti-necrotic and anti-apoptotic protection in cardiomyocytes. Furthermore, intra-coronary infusion of SIL (1 μM) in Langendorff isolated mouse hearts 10 min prior to zero-flow global I (20 min) and R (30 min) significantly reduced myocardial infarct size (from 29.4±2.4% to 16.0±3.0%; p<0.05, n=6). Co-treatment of PD98059 abrogated SIL-induced protection (33.0±5.9; n=4). To evaluate the role of ERK1/2 in delayed cardioprotection, mice were treated with saline or SIL (0.7 mg/kg i.p.) 24 hours before global I-R in Langendorff mode. PD98059 (1 mg/kg) was administered (i.p.) 30 min before the treatment of SIL. Infarct size was reduced from 27.6±3.3% in saline-treated controls to 6.9±1.2% in SIL-treated mice (P<0.05, n=6). The delayed protective effect of SIL was also abolished by PD98059 (22.5±2.3%). Western Blots revealed that SIL significantly increased phosphorylation of ERK1/2 which was blocked by PKG inhibitor, KT5823 in the heart and adult myocytes. Selective knockdown of PKG in cardiomyocytes with short hairpin RNA of PKG also blocked the phosphorylation of ERK1/2. Conclusion: SIL-induced cardioprotection involves the activation and phosphorylation of ERK which appear to be intimately linked with a PKG-dependent survival pathway. This research has received full or partial funding support from the American Heart Association, AHA Mid-Atlantic Affiliate (Maryland, North Carolina, South Carolina, Virginia & Washington, DC).

Sign in / Sign up

Export Citation Format

Share Document