Regulation of iRhom-2/Tumor Necrosis Factor-α Converting Enzyme Pathway and Oxidative Stress Protects the Renal Injury with Anemonin in Streptozotocin-Induced Diabetic Nephropathy Neonatal Rat Model

Pharmacology ◽  
2019 ◽  
Vol 104 (5-6) ◽  
pp. 258-266
Author(s):  
Lingyan Qiao ◽  
Yusheng Liu ◽  
Cheng Li ◽  
Juan Ge ◽  
Tang Li
Keyword(s):  
Diabetic Nephropathy ◽  
Renal Injury ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Kidney Tissue ◽  
Treated Group ◽  
Converting Enzyme ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Diabetic nephropathy (DN) is a chronic complication of diabetes, and thus the present investigation evaluates the nephroprotective effect of anemonin against streptozotocin (STZ)-induced DN rats. Diabetes was induced by intraperitoneal administration of STZ (50 mg/kg) on day 2 and 3 postnatal, and rats were kept as such for the duration of 12 weeks. Thereafter, rats were treated with anemonin 75 and 150 mg/kg per oral for the period 4 week which means between the period of 12–16 weeks. Effect of anemonin was estimated by determining the blood glucose, markers of nephropathy, and mediators of inflammation in the serum and activity of tumor necrosis factor-α (TNF-α)converting enzyme (TACE) in the kidney tissue of DN rats. Moreover, reverse transcriptase polymerase chain reaction and western blot assay were determined in the kidney tissue homogenate of DN rats. Histopathology study was done by Periodic acid-Schiff’s and masson staining for the pathological changes and apoptosis of podocytes in the kidney tissue of DN rats. Moreover, production of reactive oxygen species (ROS) was estimated in the kidney tissue by 2’,7’-dichlorofluorescein staining. Data of study reveal that anemonin significantly reduces (p < 0.01) the blood glucose and markers of renal injury in the serum and urine of DN rats. There was a reduction in the level of cytokines in the serum, and production of ROS and activity of TACE were reduced in the kidney tissue of the anemonin-treated group than in the DN group. Expression of iRhom-2, TACE, TNF-α, and inducible nitric oxide synthase protein and histopathology of kidney tissue were attenuated in the anemonin-treated group in DN rats. In conclusion, data of study reveal that treatment with anemonin ameliorates progression of renal injury by regulating TACE/iRhom-2 signaling pathway.

scholarly journals Macrocyclic θ-defensins suppress tumor necrosis factor-α (TNF-α) shedding by inhibition of TNF-α–converting enzyme

2018 ◽  
Vol 293 (8) ◽  
pp. 2725-2734 ◽  
Author(s):  
Justin B. Schaal ◽  
Thorsten Maretzky ◽  
Dat Q. Tran ◽  
Patti A. Tran ◽  
Prasad Tongaonkar ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Converting Enzyme ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Blockade of angiotensin-converting enzyme or tumor necrosis factor-α reverses maternal high-fat diet-induced sensitization of angiotensin II hypertension in male rat offspring

2020 ◽  
Vol 318 (2) ◽  
pp. R351-R359 ◽  
Author(s):  
Xue-Fang Wang ◽  
Jian-Dong Li ◽  
Yan-Li Huo ◽  
Yu-Ping Zhang ◽  
Zhi-Qin Fang ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Adult Offspring ◽  
Ang Ii ◽  
Converting Enzyme ◽  
High Fat ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Maternal high-fat diet (HFD) is associated with metabolic syndrome and cardiovascular diseases in adult offspring. Our previous study demonstrated that maternal HFD enhances pressor responses to ANG II or a proinflammatory cytokine (PIC), which is associated with increased expression of brain renin-angiotensin system (RAS) components and PICs in adult offspring. The present study further investigated whether inhibition of angiotensin-converting enzyme (ACE) or tumor necrosis factor-α (TNF-α) blocks sensitization of ANG II hypertension in offspring of HFD dams. All offspring were bred from dams with normal fat diet (NFD) or HFD starting two weeks before mating and maintained until weaning of the offspring. Then the weaned offspring were treated with an ACE inhibitor (captopril) or a TNF-α inhibitor (pentoxifylline) in the drinking water through the end of testing with a slow-pressor dose of ANG II. RT-PCR analyses of the lamina terminalis and paraventricular nucleus revealed upregulation of mRNA expression of several RAS components and PICs in male offspring of HFD dams when compared with age-matched offspring of NFD dams. The enhanced gene expression was attenuated by blockade of either RAS or PICs. Likewise, ANG II administration produced an augmented pressor response in offspring of HFD dams. This was abolished by either ACE or TNF-α inhibitor. Taken together, this study provides mechanistic evidence and a therapeutic strategy that systemic inhibition of the RAS and PICs can block maternal HFD-induced sensitization of ANG II hypertension, which is associated with attenuation of brain RAS and PIC expression in offspring.

TUMOR NECROSIS FACTOR-α CONVERTING ENZYME EXPRESSION IN THE JOINTS OF RHEUMATOID ARTHRITIS PATIENTS

2002 ◽  
Vol 06 (02) ◽  
pp. 63-71 ◽  
Author(s):  
Koichiro Takahi ◽  
Tetsuya Tomita ◽  
Takanobu Nakase ◽  
Motoharu Kaneko ◽  
Hiroshi Takano ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Subchondral Bone ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Mononuclear Cells ◽  
Converting Enzyme ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

The purpose of this study is to investigate the expression of tumor necrosis factor-α converting enzyme (TACE) in the synovium and subchondral bone region of patients with rheumatoid arthritis (RA) and to determine the contribution of the enzyme to the pathogenesis of RA. Joint tissues were obtained during total knee arthroplasty from patients with RA and osteoarthritis (OA). The expression of TACE and TNF-α mRNA was detected by in situ hybridization. Characterization of TACE expressing cells was performed by immunohistochemistry using serial sections. We found that TACE mRNA was expressed in both synovium and subchondral bone region and co-localized with TNF-α mRNA in RA. On the other hand, TACE mRNA expression was scarcely detectable in OA samples. TACE was expressed in mononuclear cells, such as CD3 and CD14 positive cells in RA samples. In conclusion, the expression of TACE is up-regulated in the rheumatoid synovium and subchondral bone region, and the results in this study demonstrate that TACE may be involved and play a role in the pathogenesis of RA.

scholarly journals Inactive Rhomboid Protein 2 Mediates Intestinal Inflammation by Releasing Tumor Necrosis Factor–α

2019 ◽  
Vol 26 (2) ◽  
pp. 242-253
Author(s):  
Jee Hyun Kim ◽  
Sung Wook Hwang ◽  
Jaemoon Koh ◽  
Jaeyoung Chun ◽  
Changhyun Lee ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Immune Cells ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Intestinal Inflammation ◽  
Converting Enzyme ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Inactive rhomboid 2 (iRhom2) is an essential molecule required for the maturation of tumor necrosis factor–α–converting enzyme in immune cells, which regulates TNF-α release. The aim of this study was to investigate the role of iRhom2 in intestinal inflammation.

scholarly journals P2X7 Receptor Induces Tumor Necrosis Factor-α Converting Enzyme Activation and Release to Boost TNF-α Production

2017 ◽  
Vol 8 ◽  
Author(s):  
Maria Barberà-Cremades ◽  
Ana I. Gómez ◽  
Alberto Baroja-Mazo ◽  
Laura Martínez-Alarcón ◽  
Carlos M. Martínez ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
P2x7 Receptor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Enzyme Activation ◽  
Converting Enzyme ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Tumor necrosis factor-α, kidney function, and hypertension

2017 ◽  
Vol 313 (4) ◽  
pp. F1005-F1008 ◽  
Author(s):  
Eamonn Mehaffey ◽  
Dewan S. A. Majid
Keyword(s):  
Tumor Necrosis Factor ◽  
Proinflammatory Cytokines ◽  
Renal Injury ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Low Grade ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Hypertension is considered to be a low-grade inflammatory condition characterized by the presence of various proinflammatory cytokines. Tumor necrosis factor-α (TNF-α) is a constituent of the proinflammatory cytokines that is associated with salt-sensitive hypertension (SSH) and related renal injury. Elevated angiotensin II (ANG II) and other factors such as oxidative stress conditions promote TNF-α formation. Many recent studies have provided evidence that TNF-α exerts a direct renal action by regulating hemodynamic and excretory function in the kidney. The cytokine incites a strong natriuretic response and plays a part in regulation of the intrarenal renin-angiotensin system. The exact mechanistic role of TNF-α in the development of SSH is as yet poorly understood. While TNF-α antagonism has been shown to attenuate hypertensive responses in many hypertensive animal models, contrasting findings demonstrate that the direct systemic administration of TNF-α usually induces hypotensive as well as natriuretic responses, indicating a counterregulatory role of TNF-α in SSH. Differential activities of two cell surface receptors of TNF-α (receptor type 1 and type 2) may explain the contradictory functions of TNF-α in the setting of hypertension. This short review will evaluate ongoing research studies that investigate the action of TNF-α within the kidney and its role as an influential pathophysiological variable in the development of SSH and renal injury. This information may help to develop specific TNF-α receptor targeting as an effective treatment strategy in this clinical condition.

#50 Gestational exposure of tumor necrosis factor-α (TNF-α) inhibitor drugs

2019 ◽  
Vol 88 ◽  
pp. 149-150 ◽  
Author(s):  
Erkoseoglu Ilknur ◽  
Kadioglu Mine ◽  
Cavusoglu Irem ◽  
Sisman Mulkiye ◽  
Aran Turhan ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Gestational Exposure ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor
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