iNOS enhances rat intestinal apoptosis after ischemia-reperfusion

Wu, Bin; Iwakiri, Ryuichi; Tsunada, Seiji; Utsumi, Hiroyoshi; Kojima, Masataka; Fujise, Takehiro; Ootani, Akifumi; Fujimoto, Kazuma

doi:10.1016/s0891-5849(02)00917-6

Cited by 88 publications

(88 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We have demonstrated increased levels of iNOS in the PD gastrocnemius muscle (Erekat et al, 2013). iNOS has been shown to play a critical role in mediating apoptosis (Satake et al, 2000;Song et al, 2000;Van't Hof et al, 2000;Wu et al, 2002;Sennlaub et al, 2002). For instance, iNOS has been suggested to contribute to burn injury-induced muscle apoptosis and atrophy leading to p53 activation and upregulation (Sugita et al, 2012).…”

Section: Discussionmentioning

confidence: 79%

Apoptotic Mediators are Upregulated in the Skeletal Muscle of Chronic/Progressive Mouse Model of Parkinson's Disease

Erekat

2015

The Anatomical Record

View full text Add to dashboard Cite

Apoptosis has been implicated in the pathogenesis of Parkinson disease (PD). Parkinson disease is characterized by skeletal muscle abnormalities. The aim of this study is to illustrate the impact of PD induction on the expression of apoptotic mediators. Twenty normal albino mice were randomly selected and equally divided in control and PD groups. Chronic Parkinsonism was induced in the PD group using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid (MPTP/p). After that, samples from gastrocnemius muscles were evaluated by immunohistochemistry to examine the expression of p53 and active caspase-3 in the two groups of animals. P53 and active caspase-3 expression was significantly higher in gastrocnemius skeletal muscle in PD mice compared with that in the control mice (P value <0.01). Furthermore, we show PD gastrocnemius muscle atrophy measured by significant reduction (P < 0.01) in the muscle fiber cross-sectional area. Thus, our present data suggest that PD induction increased the expression of the apoptotic mediators p53 and active caspase-3 in gastrocnemius muscle, indicating the induction of apoptosis, which was correlative with gastrocnemius muscle atrophy subsequent to the induction of PD.

show abstract

Section: Discussionmentioning

confidence: 79%

Apoptotic Mediators are Upregulated in the Skeletal Muscle of Chronic/Progressive Mouse Model of Parkinson's Disease

Erekat

2015

The Anatomical Record

View full text Add to dashboard Cite

show abstract

“…pathological state is related to the type 2 apoptosis pathway, in which cytochrome c release from the mitochondria triggers intrinsic apoptosis by opening mitochondrial permeability transition pores (16,53).…”

Section: Discussionmentioning

confidence: 99%

Fasting-induced intestinal apoptosis is mediated by inducible nitric oxide synthase and interferon-γ in rat

Ito

Uchida

Yokote

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Ito J, Uchida H, Yokote T, Ohtake K, Kobayashi J. Fastinginduced intestinal apoptosis is mediated by inducible nitric oxide synthase and interferon-␥ in rat. Am J Physiol Gastrointest Liver Physiol 298: G916 -G926, 2010. First published April 8, 2010 doi:10.1152/ajpgi.00429.2009 is associated with intestinal apoptosis in health and disease. This study aimed to investigate the role of intestinal NO in the regulation of apoptosis during fasting in rats. Male Wistar rats were divided into two groups and subcutaneously injected with saline (SA) or aminoguanidine (AG), followed by fasting for 24, 48, 60, and 72 h. At each time point, the jejunum was subjected to histological evaluation for enterocyte apoptosis by histomorphometric assessment and TUNEL analysis. We performed immunohistochemistry for inducible NO synthase (iNOS) expression in the jejunum and measured tissue nitrite levels using HPLC and 8-hydroxydeoxyguanosine adduct using ELISA, indicative of endogenous NO production and reactive oxygen species (ROS) production, respectively. Jejunal transcriptional levels of iNOS, neuronal NO synthase (nNOS), and interferon-␥ (IFN-␥) were also determined by RT-PCR. Fasting caused significant jejunal mucosal atrophy due to attenuated cell proliferation and enhanced apoptosis with increase in iNOS transcription, its protein expression in intestinal epithelial cells (IEC), and jejunal nitrite levels. However, AG treatment histologically reduced apoptosis with inhibition of fastinginduced iNOS transcription, protein expression, and nitrite production. We also observed fasting-induced ROS production and subsequent IFN-␥ transcription, which were all inhibited by AG treatment. Furthermore, we observed reduced transcriptional levels of nNOS, known to suppress iNOS activation physiologically. These results suggest that fasting-induced iNOS activation in IEC may induce apoptosis mediators such as IFN-␥ via a ROS-mediated mechanism and also a possible role of nNOS in the regulation of iNOS activity in fasting-induced apoptosis.aminoguanidine; reactive oxygen species; intestinal epithelial cells; neuronal nitric oxide synthase THE GASTROINTESTINAL EPITHELIUM is a dynamic tissue characterized by a high cellular turnover rate with a balance between cell proliferation and cell apoptosis, consequently leading to renewal of the entire intestinal epithelium every 3-5 days (9,19). This single layer of cells lining the gut lumen acts as a barrier against harmful intraluminal entities, including foreign antigens, microorganisms, and toxins, and also acts as a selective filter allowing the translocation of essential dietary nutrients, electrolytes, and water. However, these physiological functions are occasionally impaired under pathological conditions such as inflammation and ischemia-reperfusion and are accompanied by intestinal histological changes, including apoptosis.Fasting is likely a physiological challenge evoking a response to the absence of luminal nutrients by functional and morphological changes, including intestinal epithe...

show abstract

“…Several members (caspase-8, -9, and -10) contain a large prodomain and are initiators of the apoptotic signaling cascade, whereas other members (caspase-3, -6, and -7) possess a small prodomain and participate in the execution phase of apoptosis. Our previous studies showed that ischemia/ reperfusion-induced gastrointestinal mucosal apoptosis occurs via the release of cytochrome c from the mitochondria, which then leads to the activation of caspase-9 and caspase-6 [37][38][39][40]. The current data suggest that PHT-induced apoptosis has a different mechanism from that described for ischemia/reperfusion in the gastrointestinal mucosa.…”

Section: Discussionmentioning

confidence: 53%

Downregulation of cyclooxygenase-1 is involved in gastric mucosal apoptosis via death signaling in portal hypertensive rats

Zeng

Ying

et al. 2009

Cell Res

Self Cite

View full text Add to dashboard Cite

Portal hypertension (PHT) gastropathy is a frequent complication of liver cirrhosis and one of the leading causes of death from cirrhosis. Apoptosis is widely considered to be an active energy-dependent mode of cell death and a distinct entity from necrotic cell death. It is unclear whether gastric mucosal apoptosis is involved in PHT gastropathy. Prostaglandins (PGs) produced through cyclooxygenase (COX) are thought to play a key role in protection of the gastrointestinal mucosa from injury and apoptosis. However, the role of COX in PHT gastropathy is still not clearly understood. The aims of this study were to investigate whether (1) gastric mucosal apoptosis is involved in PHT gastropathy and (2) downregulation of COX contributes to this apoptosis. In this study, we show that gastric mucosal apoptosis was remarkably increased while mucosal proliferation was inhibited in PHT rats. Gastric mucosal COX-1 was significantly suppressed at both the mRNA and protein levels, and PGE 2 was reduced in PHT rats. Further, PGE 2 treatment suppressed gastric mucosal apoptosis in PHT rats. However, gastric mucosal COX-2 levels did not differ between sham-operated rats and PHT rats. Gastric mucosal levels of tumor necrosis factor-α (TNF-α) and Fas ligand, but not TNF-related apoptosis-inducing ligand, were increased, and activated caspase-8 and caspase-3 levels were upregulated in PHT rats. The release of cytochrome c from the mitochondria to the cytosol was not observed in PHT rats. Our data indicate that downregulation of COX-1 is involved in gastric mucosal apoptosis via death signaling-mediated type-I cell death in PHT rats.

show abstract

iNOS enhances rat intestinal apoptosis after ischemia-reperfusion

Cited by 88 publications

References 48 publications

Apoptotic Mediators are Upregulated in the Skeletal Muscle of Chronic/Progressive Mouse Model of Parkinson's Disease

Apoptotic Mediators are Upregulated in the Skeletal Muscle of Chronic/Progressive Mouse Model of Parkinson's Disease

Fasting-induced intestinal apoptosis is mediated by inducible nitric oxide synthase and interferon-γ in rat

Downregulation of cyclooxygenase-1 is involved in gastric mucosal apoptosis via death signaling in portal hypertensive rats

Contact Info

Product

Resources

About