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835 results on '"Simon, Melvin I."'

1. Wolfram Syndrome protein, Miner1, regulates sulphydryl redox status, the unfolded protein response, and Ca2+ homeostasis

Author

Wiley, Sandra E, Andreyev, Alexander Y, Divakaruni, Ajit S, Karisch, Robert, Perkins, Guy, Wall, Estelle A, van der Geer, Peter, Chen, Yi‐Fan, Tsai, Ting‐Fen, Simon, Melvin I, Neel, Benjamin G, Dixon, Jack E, and Murphy, Anne N

Subjects
Biochemistry and Cell Biology, Biological Sciences, Rare Diseases, 2.1 Biological and endogenous factors, Adenosine Triphosphate, Animals, Antioxidants, Autophagy-Related Proteins, Calcium, Carrier Proteins, Cell Line, Glutathione, Glutathione Disulfide, Mice, Mitochondria, NAD, Nerve Tissue Proteins, Oxidation-Reduction, Sulfhydryl Compounds, Unfolded Protein Response, Wolfram Syndrome, calcium, endoplasmic reticulum, mitochondria, oxidative stress, Medical and Health Sciences, Biochemistry and cell biology
Abstract

Miner1 is a redox-active 2Fe2S cluster protein. Mutations in Miner1 result in Wolfram Syndrome, a metabolic disease associated with diabetes, blindness, deafness, and a shortened lifespan. Embryonic fibroblasts from Miner1(-/-) mice displayed ER stress and showed hallmarks of the unfolded protein response. In addition, loss of Miner1 caused a depletion of ER Ca(2+) stores, a dramatic increase in mitochondrial Ca(2+) load, increased reactive oxygen and nitrogen species, an increase in the GSSG/GSH and NAD(+)/NADH ratios, and an increase in the ADP/ATP ratio consistent with enhanced ATP utilization. Furthermore, mitochondria in fibroblasts lacking Miner1 displayed ultrastructural alterations, such as increased cristae density and punctate morphology, and an increase in O2 consumption. Treatment with the sulphydryl anti-oxidant N-acetylcysteine reversed the abnormalities in the Miner1 deficient cells, suggesting that sulphydryl reducing agents should be explored as a treatment for this rare genetic disease.

Published
2013

19. Novel Form of Adaptation in Mouse Retinal Rods Speeds Recovery of Phototransduction

Author

Krispel, Claudia M, Chen, Ching-Kang, Simon, Melvin I, and Burns, Marie E

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Ecology, Neurosciences, Eye Disease and Disorders of Vision, Adaptation, Physiological, Animals, Mice, Mice, Inbred C57BL, Mice, Knockout, Photic Stimulation, Retinal Rod Photoreceptor Cells, Vision, Ocular, photoreceptors, GTP-binding proteins, kinetics, phototransduction, knock-out mice, Physiology, Medical Physiology, Biochemistry and cell biology, Zoology, Medical physiology
Abstract

Photoreceptors of the retina adapt to ambient light in a manner that allows them to detect changes in illumination over an enormous range of intensities. We have discovered a novel form of adaptation in mouse rods that persists long after the light has been extinguished and the rod's circulating dark current has returned. Electrophysiological recordings from individual rods showed that the time that a bright flash response remained in saturation was significantly shorter if the rod had been previously exposed to bright light. This persistent adaptation did not decrease the rate of rise of the response and therefore cannot be attributed to a decrease in the gain of transduction. Instead, this adaptation was accompanied by a marked speeding of the recovery of the response, suggesting that the step that rate-limits recovery had been accelerated. Experiments on knockout rods in which the identity of the rate-limiting step is known suggest that this adaptive acceleration results from a speeding of G protein/effector deactivation.

Published
2003

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