Histomorphometric analysis of diabetic osteopenia in streptozotocin-induced diabetic mice: A possible role of oxidative stress

Bone ◽  
2007 ◽  
Vol 40 (5) ◽  
pp. 1408-1414 ◽  
Author(s):  
Yasuhiro Hamada ◽  
Sohei Kitazawa ◽  
Riko Kitazawa ◽  
Hideki Fujii ◽  
Masato Kasuga ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Mice ◽  
Histomorphometric Analysis ◽  
Diabetic Osteopenia

scholarly journals Long Non-coding RNA XIST Attenuates Diabetic Peripheral Neuropathy by Inducing Autophagy Through MicroRNA-30d-5p/sirtuin1 Axis

2021 ◽  
Vol 8 ◽  
Author(s):  
Bei-Yan Liu ◽  
Lin Li ◽  
Li-Wei Bai ◽  
Chang-Shui Xu
Keyword(s):  
Oxidative Stress ◽  
Peripheral Neuropathy ◽  
Schwann Cells ◽  
Diabetic Peripheral Neuropathy ◽  
Beclin 1 ◽  
Diabetic Mice ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Long Non Coding Rna

Diabetic peripheral neuropathy (DPN) is a prevalent diabetes mellitus (Feldman et al., 2017) complication and the primary reason for amputation. Meanwhile, long non-coding RNAs (lncRNAs) are a type of regulatory non-coding RNAs (ncRNAs) that broadly participate in DPN development. However, the correlation of lncRNA X-inactive specific transcript (XIST) with DPN remains unclear. In this study, we were interested in the role of XIST in the modulation of DPN progression. Significantly, our data showed that the expression of XIST and sirtuin1 (SIRT1) was inhibited, and the expression of microRNA-30d-5p (miR-30d-5p) was enhanced in the trigeminal sensory neurons of the diabetic mice compared with the normal mice. The levels of LC3II and Beclin-1 were inhibited in the diabetic mice. The treatment of high glucose (HG) reduced the XIST expression in Schwann cells. The apoptosis of Schwann cells was enhanced in the HG-treated cells, but the overexpression of XIST could block the effect in the cells. Moreover, the levels of LC3II and Beclin-1 were reduced in the HG-treated Schwann cells, while the overexpression of XIST was able to reverse this effect. The HG treatment promoted the production of oxidative stress, while the XIST overexpression could attenuate this result in the Schwann cells. Mechanically, XIST was able to sponge miR-30d-5p and miR-30d-5p-targeted SIRT1 in the Schwann cells. MiR-30d-5p inhibited autophagy and promoted oxidative stress in the HG-treated Schwann cells, and SIRT1 presented a reversed effect. MiR-30d-5p mimic or SIRT1 depletion could reverse XIST overexpression-mediated apoptosis and autophagy of the Schwann cells. Thus, we concluded that XIST attenuated DPN by inducing autophagy through miR-30d-5p/SIRT1 axis. XIST and miR-30d-5p may be applied as the potential targets for DPN therapy.

Thioredoxin-1 overexpression in transgenic mice attenuates streptozotocin-induced diabetic osteopenia: A novel role of oxidative stress and therapeutic implications

Bone ◽  
2009 ◽  
Vol 44 (5) ◽  
pp. 936-941 ◽  
Author(s):  
Yasuhiro Hamada ◽  
Hideki Fujii ◽  
Riko Kitazawa ◽  
Junji Yodoi ◽  
Sohei Kitazawa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transgenic Mice ◽  
Therapeutic Implications ◽  
Thioredoxin 1 ◽  
Diabetic Osteopenia

scholarly journals Role of Advanced Glycation Products with Oxidative Stress in Resistance Artery Dysfunction in Type 2 Diabetic mice

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Jun Su ◽  
Pamela Lucchesi ◽  
Yasuhiro Suzuki ◽  
Bashir M Rezk ◽  
Desiree I Palen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Mice ◽  
Resistance Artery ◽  
Advanced Glycation ◽  
Type 2 Diabetic

scholarly journals The Role of Heme Oxygenase 1 in the Protective Effect of Caloric Restriction against Diabetic Cardiomyopathy

2019 ◽  
Vol 20 (10) ◽  
pp. 2427 ◽  
Author(s):  
Maayan Waldman ◽  
Vadim Nudelman ◽  
Asher Shainberg ◽  
Romy Zemel ◽  
Ran Kornwoski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Beneficial Effect ◽  
Heme Oxygenase ◽  
Diabetic Cardiomyopathy ◽  
High Glucose ◽  
Heme Oxygenase 1 ◽  
Ros Production ◽  
Diabetic Mice ◽  
Protein Levels

Type 2 diabetes mellitus (DM2) leads to cardiomyopathy characterized by cardiomyocyte hypertrophy, followed by mitochondrial dysfunction and interstitial fibrosis, all of which are exacerbated by angiotensin II (AT). SIRT1 and its transcriptional coactivator target PGC-1α (peroxisome proliferator-activated receptor-γ coactivator), and heme oxygenase-1 (HO-1) modulates mitochondrial biogenesis and antioxidant protection. We have previously shown the beneficial effect of caloric restriction (CR) on diabetic cardiomyopathy through intracellular signaling pathways involving the SIRT1–PGC-1α axis. In the current study, we examined the role of HO-1 in diabetic cardiomyopathy in mice subjected to CR. Methods: Cardiomyopathy was induced in obese diabetic (db/db) mice by AT infusion. Mice were either fed ad libitum or subjected to CR. In an in vitro study, the reactive oxygen species (ROS) level was determined in cardiomyocytes exposed to different glucose levels (7.5–33 mM). We examined the effects of Sn(tin)-mesoporphyrin (SnMP), which is an inhibitor of HO activity, the HO-1 inducer cobalt protoporphyrin (CoPP), and the SIRT1 inhibitor (EX-527) on diabetic cardiomyopathy. Results: Diabetic mice had low levels of HO-1 and elevated levels of the oxidative marker malondialdehyde (MDA). CR attenuated left ventricular hypertrophy (LVH), increased HO-1 levels, and decreased MDA levels. SnMP abolished the protective effects of CR and caused pronounced LVH and cardiac metabolic dysfunction represented by suppressed levels of adiponectin, SIRT1, PPARγ, PGC-1α, and increased MDA. High glucose (33 mM) increased ROS in cultured cardiomyocytes, while SnMP reduced SIRT1, PGC-1α levels, and HO activity. Similarly, SIRT1 inhibition led to a reduction in PGC-1α and HO-1 levels. CoPP increased HO-1 protein levels and activity, SIRT1, and PGC-1α levels, and decreased ROS production, suggesting a positive feedback between SIRT1 and HO-1. Conclusion: These results establish a link between SIRT1, PGC-1α, and HO-1 signaling that leads to the attenuation of ROS production and diabetic cardiomyopathy. CoPP mimicked the beneficial effect of CR, while SnMP increased oxidative stress, aggravating cardiac hypertrophy. The data suggest that increasing HO-1 levels constitutes a novel therapeutic approach to protect the diabetic heart. Brief Summary: CR attenuates cardiomyopathy, and increases HO-1, SIRT activity, and PGC-1α protein levels in diabetic mice. High glucose reduces adiponectin, SIRT1, PGC1-1α, and HO-1 levels in cardiomyocytes, resulting in oxidative stress. The pharmacological activation of HO-1 activity mimics the effect of CR, while SnMP increased oxidative stress and cardiac hypertrophy. These data suggest the critical role of HO-1 in protecting the diabetic heart.

scholarly journals Role of Advanced Glycation End Products With Oxidative Stress in Resistance Artery Dysfunction in Type 2 Diabetic Mice

2008 ◽  
Vol 28 (8) ◽  
pp. 1432-1438 ◽  
Author(s):  
Jun Su ◽  
Pamela A. Lucchesi ◽  
Romer A. Gonzalez-Villalobos ◽  
Desiree I. Palen ◽  
Bashir M. Rezk ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Advanced Glycation End Products ◽  
Diabetic Mice ◽  
Resistance Artery ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Type 2 Diabetic

scholarly journals SP600125 suppresses Keap1 expression and results in NRF2-mediated prevention of diabetic nephropathy

2018 ◽  
Vol 60 (2) ◽  
pp. 145-157 ◽  
Author(s):  
Huan Zhang ◽  
Xiuxia Liu ◽  
Shanshan Zhou ◽  
Ye Jia ◽  
Ying Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Nuclear Translocation ◽  
Mesangial Cells ◽  
Critical Role ◽  
Antioxidant Defense System ◽  
Related Factor ◽  
Diabetic Mice ◽  
Nrf2 Protein

c-Jun N-terminal kinase (JNK) contributes to the pathogenesis of diabetic nephropathy (DN). The JNK inhibitor SP600125 was reported to ameliorate DN. However, the mechanism remained unclear. We previously reported that SP600125 activated nuclear factor erythroid 2-related factor 2 (NRF2), a governor of the cellular antioxidant defense system, in the aortas of the diabetic mice. Given the critical role of NRF2 in preventing DN, the present study aimed to test whether or not NRF2 is required for SP600125’s protection against DN. To test the role of NRF2 in SP600125’s effect, streptozotocin-induced C57BL/6 wild-type (WT) and Nrf2-knockout (KO) diabetic mice were treated in the presence or absence of SP600125, for 24 weeks. To explore the mechanism by which SP600125 activates NRF2, mouse mesangial cells (MMCs) were treated with high glucose (HG), in the presence or absence of either SP600125 or JNK siRNA. SP600125 significantly attenuated the diabetes-induced renal oxidative stress, inflammation, fibrosis, pathological change and dysfunction in the WT, but not the Nrf2 KO mice. SP600125 inactivated JNK, inhibited kelch-like ECH-associated protein 1 expression, preserved NRF2 protein and facilitated its nuclear translocation in the kidneys of the WT mice, the effects of which were similarly produced by either SP600125 or JNK siRNA in HG-treated MMCs. Further, both SP600125 and JNK siRNA alleviated HG-induced mesangial oxidative stress and expression of inflammatory and fibrotic genes. The present study demonstrates that NRF2 is required for SP600125’s protection against DN. SP600125 activates NRF2 possibly via inhibition of JNK-induced Keap1 expression.

Angiotensin-(1–7) prevents systemic hypertension, attenuates oxidative stress and tubulointerstitial fibrosis, and normalizes renal angiotensin-converting enzyme 2 and Mas receptor expression in diabetic mice

2015 ◽  
Vol 128 (10) ◽  
pp. 649-663 ◽  
Author(s):  
Yixuan Shi ◽  
Chao-Sheng Lo ◽  
Ranjit Padda ◽  
Shaaban Abdo ◽  
Isabelle Chenier ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Converting Enzyme ◽  
Renal Injury ◽  
Receptor Expression ◽  
Systemic Hypertension ◽  
Converting Enzyme ◽  
Diabetic Mice ◽  
Angiotensin Converting Enzyme 2 ◽  
Mas Receptor

In summary, our data indicate an important role of Ang-(1–7) in inhibiting intrarenal oxidative stress and subsequent prevention of the development of hypertension and renal injury in diabetic mice.

scholarly journals Relationship between oxidative stress and diabetic osteopenia in premenopausal rats

2010 ◽  
Vol 46 (3) ◽  
pp. 539-549 ◽  
Author(s):  
Valéria Morgiana Gualberto Duarte ◽  
Alanna de Sousa Rodrigues ◽  
Luciana Augusto de Rezende ◽  
Ana Maria de Oliveira Ramos ◽  
Rodrigo Medeiros de Souza ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Antioxidant Defense ◽  
Biomechanical Testing ◽  
Diabetic Rats ◽  
Histomorphometric Analysis ◽  
Trabecular Thickness ◽  
Peroxidation Index ◽  
The Relationship ◽  
Diabetic Osteopenia

The relationship between lipid peroxidation, antioxidant defense and diabetic osteopenia remains unclear. This study evaluated the relationship among lipid peroxidation index, antioxidant defense parameters and bone metabolism in a premenopausal diabetic model using measures including thiobarbituric acid-reactive substances concentration (TBARS) and reduced glutathione (GSH) content in brain homogenates, histomorphometric analysis, biomechanical testing and bone mineral density (BMD). Female Wistar rats with regular estrous cycle were divided into two groups: Group 1: control rats (n = 15) and Group 2: diabetic rats (n = 15). Diabetes was induced by alloxan and confirmed by glycemia >250 mg/dL. The lipid peroxidation index, measured by TBARS concentration, showed a significant increase (p<0.05) in diabetic animals in comparison to control animals. However, the antioxidant parameter measured by GSH content, was significantly lower (p<0.05) in diabetic animals. Histomorphometric analysis showed a significant increase (p<0.05) in femoral trabecular separation together with a significant decrease (p<0.05) in trabecular thickness, and reduced trabecular bone volume in diabetic rats. Moreover, biomechanical testing and BMD values were significantly lower (p<0.05) in the diabetic group. Thus, our results demonstrated that increased lipid peroxidation and altered antioxidant defense could be related to the development of oxidative stress and diabetic osteopenia in premenopausal rats.

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