Mitochondrial activity contributes to impaired renal metabolic homeostasis and renal pathology in STZ-induced diabetic mice.

Mitochondrial activity contributes to impaired renal metabolic homeostasis and renal pathology in STZ-induced diabetic mice. Am J Physiol Renal Physiol. 2019 Jul 03;: Authors: Wu M, Li S, Yu X, Chen W, Ma H, Shao C, Zhang Y, Zhang A, Huang S, Jia Z Abstract Diabetic nephropathy (DN) has become the main cause of end-stage renal disease worldwide while the efficacy of current therapeutic strategies on DN remains unsatisfactory. Recent researches reported the involvement of metabolic re-arrangement in the pathological process of DN, and of all the disturbances in metabolism, mitochondria serve as key regulatory hubs. In the present study, high-resolution mass spectrometry-based none-target metabolomics was employed to uncover the metabolic characteristics of early diabetic kidney with or without the inhibition of mitochondrial activity. At first, we observed a moderate enhancement of mitochondrial complex-1 activity in diabetic kidney, which was completely normalized by a specific mitochondrial complex-1 inhibitor rotenone (ROT). Meanwhile, metabolomics data indicated over-activated pentose phosphate pathway, purine and pyrimidine metabolism, hexosamine biosynthetic pathway, and Kreb cycle, which were strikingly corrected by ROT. In addition, ROT also strikingly corrected imbalanced redox homeostasis possibly by increasing the ratio of antioxidant metabolites GSH and NAPDH against their oxidative form. In agreement with the improved metabolic status and oxi...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research

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ConclusionIn conclusion PKR activation plays an important role in the pathogenesis of vascular inflammation and remodelling, and therapeutically targeting PKR could be an effective approach to treat the abnormalities associated with vascular complications.
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research
Abstract Muscle atrophy is closely associated with many diseases, including diabetes and cardiac failure. Growing evidence has shown that mitochondrial dysfunction is related to muscle atrophy; however, the underlying mechanisms are still unclear. To elucidate how mitochondrial dysfunction causes muscle atrophy, we used hindlimb-immobilized mice. Mitochondrial function is optimized by balancing mitochondrial dynamics, and we observed that this balance shifted towards mitochondrial fission and that MuRF1 and atrogin-1 expression levels were elevated in these mice. We also found that the expression of yeast mitochon...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
Abstract SUGCT (C7orf10) is a mitochondrial enzyme that synthesizes glutaryl-CoA from glutarate in tryptophan and lysine catabolism, but it has not been studied in vivo. Although mutations in Sugct lead to Glutaric Aciduria Type 3 disease in humans, patients remain largely asymptomatic despite high levels of glutarate in the urine. To study the disease mechanism, we generated SugctKO mice and uncovered imbalanced lipid and acylcarnitine metabolism in kidney in addition to changes in the gut microbiome. After SugctKO mice were treated with antibiotics, metabolites were comparable to WT, indicating that the microbio...
Source: Cellular and Molecular Life Sciences : CMLS - Category: Cytology Authors: Tags: Cell Mol Life Sci Source Type: research
This article presents the original descriptions of some recent physics mechanisms (based on the thermodynamic, kinetic, and quantum tunnel effects) providing stable 2H/1H isotope fractionation, leading to the accumulation of particular isotopic forms in intra- or intercellular space, including the molecular effects of deuterium interaction with 18O/17O/16O, 15N/14N, 13C/12C, and other stable biogenic isotopes. These effects were observed mainly at the organelle (mitochondria) and cell levels. A new hypothesis for heavy nonradioactive isotope fractionation in living systems via neutron effect realization is discussed. The c...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
Abstract Mitochondria have an essential function in cell survival due to their role in bioenergetics, reactive oxygen species generation, calcium buffering, and other metabolic activities. Mitochondrial dysfunctions are commonly found in neurodegenerative diseases (NDs), and diabetes is a risk factor for NDs. However, the role of mitochondria in diabetic neurodegeneration is still unclear. In the current study, we reviewed the latest evidence on the role of mitochondrial dysfunctions in the development of diabetes-related NDs and the underlying molecular mechanisms. Hypoglycemic agents, especially metformin, have ...
Source: Am J Physiol Endocri... - Category: Endocrinology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research
CONCLUSION: We showed that mitochondrial ceramide accumulation may result in podocyte damage through ROS production. Therefore, this signaling pathway could become a pharmacological target to abate the development of diabetic kidney disease. PMID: 31701696 [PubMed - as supplied by publisher]
Source: Diabetes and Metabolism Journal - Category: Endocrinology Tags: Diabetes Metab J Source Type: research
In conclusion, high-dose NR induces the onset of WAT dysfunction, which may in part explain the deterioration of metabolic health. Towards a Rigorous Definition of Cellular Senescence https://www.fightaging.org/archives/2019/11/towards-a-rigorous-definition-of-cellular-senescence/ The accumulation of lingering senescent cells is a significant cause of aging, disrupting tissue function and generating chronic inflammation throughout the body. Even while the first senolytic drugs capable of selectively destroying these cells already exist, and while a number of biotech companies are working on the productio...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Authors: Kang YE, Kim HJ, Shong M Abstract Obesity results in an inflammatory microenvironment in adipose tissue, leading to the deterioration of tissue protective mechanisms. Although recent studies suggested the importance of type 2 immunity in an anti-inflammatory microenvironment in adipose tissue, the regulatory effects of T helper 2 (Th2) cytokines on systemic metabolic regulation are not fully understood. Recently, we identified the roles of the Th2 cytokine (interleukin 4 [IL-4] and IL-13)-induced adipokine, growth differentiation factor 15 (GDF15), in adipose tissue in regulating systemic glucose metabolis...
Source: Diabetes and Metabolism Journal - Category: Endocrinology Tags: Diabetes Metab J Source Type: research
Abstract Present-day drug therapies provide clear beneficial effects as many diseases can be driven into remission and the symptoms of others can be efficiently managed; however, the success of many drugs is limited due to both patient non-compliance and adverse off-target or toxicity-induced effects. There is emerging evidence that many of these side effects are caused by drug-induced impairment of mitochondrial function and eventual mitochondrial dysfunction. It is imperative to understand how and why drug-induced side effects occur and how mitochondrial function is affected. In an aging population, age-associat...
Source: Biochemical Society Transactions - Category: Biochemistry Authors: Tags: Biochem Soc Trans Source Type: research
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