Suppressor of Cytokine Signaling 1 Inhibits Apoptosis of Islet Grafts Through Caspase 3 and Apoptosis-Inducing Factor Pathways in Rats

Suo, Guangjun; Qin, Jie; Zhong, Cuiping; Zhao, Zhengwei

doi:10.1016/j.transproceed.2010.04.039

Cited by 14 publications

(19 citation statements)

References 11 publications

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“…TNF-alpha and other stimuli can reduce the mitochondrial transmembrane potential resulting in release of mitochondrial factors such as cytochrome c or AIF. AIF rapidly translocates from mitochondria to the nucleus and induces nuclear fragmentation and cell death by autophagic degeneration (Suo et al, 2010;Munemasa et al, 2010;Tezel and Yang, 2004;Lorenzo et al, 1999;Daugas et al, 2000). The translocation of AIF has been implicated in several types of neuronal death, including photoreceptor and ganglion cell death (Hisatomi et al, 2001;Mizukoshi et al, 2010;Thapa et al, 2012;Sanges et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Phosphodiesterase inhibition induces retinal degeneration, oxidative stress and inflammation in cone-enriched cultures of porcine retina

Cámara

Sequedo

Gómez‐Pinedo

et al. 2013

Experimental Eye Research

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Inherited retinal degenerations affecting both rod and cone photoreceptors constitute one of the causes of incurable blindness in the developed world. Cyclic guanosine monophosphate (cGMP) is crucial in the phototransduction and, mutations in genes related to its metabolism are responsible for different retinal dystrophies. cGMP-degrading phosphodiesterase 6 (PDE6) mutations cause around 4-5% of the retinitis pigmentosa, a rare form of retinal degeneration. The aim of this study was to evaluate whether pharmacological PDE6 inhibition induced retinal degeneration in cone-enriched cultures of porcine retina similar to that found in murine models. PDE6 inhibition was induced in cone-enriched retinal explants from pigs by Zaprinast. PDE6 inhibition induced cGMP accumulation and triggered retinal degeneration, as determined by TUNEL assay. Western blot analysis and immunostaining indicated that degeneration was accompanied by caspase-3, calpain-2 activation and poly (ADP-ribose) accumulation. Oxidative stress markers, total antioxidant capacity, thiobarbituric acid reactive substances (TBARS) and nitric oxide measurements revealed the presence of oxidative damage. Elevated TNF-alpha and IL-6, as determined by enzyme immunoassay, were also found in cone-enriched retinal explants treated with Zaprinast. Our study suggests that this ex vivo model of retinal degeneration in porcine retina could be an alternative model for therapeutic research into the mechanisms of photoreceptor death in cone-related diseases, thus replacing or reducing animal experiments.

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Section: Discussionmentioning

confidence: 99%

Phosphodiesterase inhibition induces retinal degeneration, oxidative stress and inflammation in cone-enriched cultures of porcine retina

Cámara

Sequedo

Gómez‐Pinedo

et al. 2013

Experimental Eye Research

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“…SOCS3 transgenic islets also displayed prolonged graft survival when transplanted into diabetic allogeneic BALB/c mice. Yet another study demonstrated that transplantation of chimeric adenovirus vector Ad5F35-SOCS1-infected islets into STZ-induced diabetic recipients significantly prolonged functional graft survival through caspase-3-dependent and intranuclear apoptosis inducing factor (AIF)-caspase-independent pathways [144]. Down-regulation of interferon regulatory factor-1 (IRF-1) signaling by SOCS-1 expression in b-cell also delayed islet allograft rejection [145].…”

Section: Pathogenesis Of Type 1 Diabetes Mellitusmentioning

confidence: 99%

The Immunosuppressive Role of Adenosine A2A Receptors in Ischemia Reperfusion Injury and Islet Transplantation

Chhabra¹,

Linden²,

Lobo³

et al. 2012

CDR

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Activation of adenosine A2A receptors (A2AR) reduces inflammation by generally inhibiting the activation of pro-inflammatory cells, decreasing endothelial adhesion molecule expression and reducing the release of proinflammatory cytokine mediators. Numerous preclinical studies using selective A2AR agonists, antagonists, A2AR knockout as well as chimeric mice have suggested the therapeutic potential of A2AR agonists for the treatment of ischemia reperfusion injury (IRI) and autoimmune diseases. This review summarizes the immunosuppressive actions of A2AR agonists in murine IRI models of liver, kidney, heart, lung and CNS, and gives details on the cellular effects of A2AR activation in neutrophils, macrophages, dendritic cells, natural killer cells, NKT cells, T effector cells and CD4+CD25+FoxP3+ T regulatory cells. This is discussed in the context of cytokine mediators involved in inflammatory cascades. Whilst the role of adenosine receptor agonists in various models of autoimmune disease has been well-documented, very little information is available regarding the role of A2AR activation in type 1 diabetes mellitus (T1DM). An overview of the pathogenesis of T1DM as well as early islet graft rejection in the immediate peri-transplantation period offers insight regarding the use of A2AR agonists as a beneficial intervention in clinical islet transplantation, promoting islet graft survival, minimizing early islet loss and reducing the number of islets required for successful transplantation, thereby increasing the availability of this procedure to a greater number of recipients. In summary, the use of A2AR agonists as a clinical intervention in IRI and as an adjunct to clinical immunesuppressive regimen in islet transplantation is highlighted.

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“…When the cells are stimulated by external physiological or pathological factors, apoptosis is initiated and the caspases are activated through a series of cleavage cascading reactions. Due to cascade enlarging effects and positive feedback, a large number of proteases are activated instantly, which causes simultaneous and rapid decomposition of a variety of ‘cell death substrates’, eventually leading to chromosome breakage, morphological changes of cells and finally apoptosis (12). …”

Section: Discussionmentioning

confidence: 99%

Effect of limb ischemic preconditioning on myocardial apoptosis-related proteins in ischemia-reperfusion injury

Jianzhi

Zhao

Wang

et al. 2013

Experimental and Therapeutic Medicine

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The aim of this study was to investigate the effect of limb ischemic preconditioning (LIPC) on myocardial apoptosis in myocardial ischemia-reperfusion injury (MIRI), as well as the regulation of caspase-3 and the B cell lymphoma 2 (Bcl-2) gene in LIPC. A total of 50 rats were divided randomly into 5 groups (n=10). Four rats in each group were drawn out for detection of apoptosis. The sham, MIRI and LIPC groups underwent surgery without additional treatment. In the LY294002 group, LY294002 preconditioning was administered 15 min before reperfusion. In the LY294002+LIPC group, following LIPC, LY294002 was administered 15 min before reperfusion. The relative expression of myocardial Bcl-2 and caspase-3 mRNA and the apoptotic index for each group were determined by reverse transcription-polymerase chain reaction (RT-PCR) and terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), respectively. The ultrastructure of the cardiac muscle tissues was observed by election microscopy. Compared with the sham group, the expression of caspase-3 mRNA in the MIRI group significantly increased (P<0.05) and the expression of Bcl-2 mRNA clearly decreased. Compared with the MIRI group, LIPC reduced the expression of caspase-3 and increased the expression of Bcl-2 mRNA (P<0.05). There were no significant differences between the LY294002+LIPC group and the MIRI group. Compared with the sham group, the apoptotic index of myocardial cells in the MIRI group significantly increased (P<0.05). Compared with the MIRI group, LIPC significantly decreased the apoptotic index of myocardial cells (P<0.05) and LY294002 increased the apoptotic index of myocardial cells. Compared with the LIPC group, LY294002+LIPC significantly increased the apoptotic index of myocardial cells (P<0.05). There were no significant differences between the LY294002+LIPC and MIRI groups. In conclusion, LIPC increased the expression of Bcl-2 and decreased caspase-3 mRNA and apoptosis in myocardial tissue following MIRI. Therefore, LIPC plays a protective role in myocardial tissue.

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Suppressor of Cytokine Signaling 1 Inhibits Apoptosis of Islet Grafts Through Caspase 3 and Apoptosis-Inducing Factor Pathways in Rats

Cited by 14 publications

References 11 publications

Phosphodiesterase inhibition induces retinal degeneration, oxidative stress and inflammation in cone-enriched cultures of porcine retina

Phosphodiesterase inhibition induces retinal degeneration, oxidative stress and inflammation in cone-enriched cultures of porcine retina

The Immunosuppressive Role of Adenosine A2A Receptors in Ischemia Reperfusion Injury and Islet Transplantation

Effect of limb ischemic preconditioning on myocardial apoptosis-related proteins in ischemia-reperfusion injury

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