A specific phosphorylation regulates the protective role of αA-crystallin in diabetes

JCI Insight
Anne RuebsamPatrice E Fort

Abstract

Neurodegeneration is a central aspect of the early stages of diabetic retinopathy, the primary ocular complication associated with diabetes. While progress has been made to improve the vascular perturbations associated with diabetic retinopathy, there are still no treatment options to counteract the neuroretinal degeneration associated with diabetes. Our previous work suggested that the molecular chaperones α-crystallins could be involved in the pathophysiology of diabetic retinopathy; however, the role and regulation of α-crystallins remained unknown. In the present study, we demonstrated the neuroprotective role of αA-crystallin during diabetes and its regulation by its phosphorylation on residue 148. We further characterized the dual role of αA-crystallin in neurons and glia, its essential role for neuronal survival, and its direct dependence on phosphorylation on this residue. These findings support further evaluation of αA-crystallin as a treatment option to promote neuron survival in diabetic retinopathy and neurodegenerative diseases in general.

References

Feb 4, 1997·Proceedings of the National Academy of Sciences of the United States of America·J P BradyE F Wawrousek
Aug 26, 1998·The Journal of Clinical Investigation·A J BarberT W Gardner
Jun 12, 2003·American Journal of Physiology. Endocrinology and Metabolism·Chad E N ReiterThomas W Gardner
Dec 9, 2003·The Journal of Biological Chemistry·Xiaohua WuThomas W Gardner
Feb 27, 2004·Investigative Ophthalmology & Visual Science·Heather A Hancock, Timothy W Kraft
Aug 25, 2004·Investigative Ophthalmology & Visual Science·Pamela M MartinSylvia B Smith
May 26, 2005·Investigative Ophthalmology & Visual Science·Alistair J BarberSarah K Bronson
Nov 29, 2005·Archives of Biochemistry and Biophysics·P Anil KumarG Bhanuprakash Reddy
Oct 13, 2006·Molecular and Cellular Biology·Nirit Mor-VakninDavid M Markovitz
Apr 5, 2007·Nature Protocols·Andrej ShevchenkoMatthias Mann
Jun 15, 2007·Nature·Shalina S OusmanLawrence Steinman
Oct 13, 2007·Molecular and Cellular Neurosciences·Debasish SinhaJ Samuel Zigler
Jan 30, 2008·Infection and Immunity·Emily A WhistonMeredith S Gregory
Jan 30, 2008·Current Protocols in Cell Biology·Clotilde ThéryAled Clayton
Dec 22, 2009·Blood·Satoru KaseDavid R Hinton
Jun 18, 2010·Investigative Ophthalmology & Visual Science·Steven F AbcouwerDavid A Antonetti
Apr 7, 2011·Investigative Ophthalmology & Visual Science·Mandy K Losiewicz, Patrice E Fort
Aug 11, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ahmet AracGary K Steinberg
May 9, 2012·Frontiers in Immunology·Sara E BrownellLawrence Steinman
Oct 19, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Armelle KlopsteinRubèn López-Vales
May 28, 2013·Molecular Neurobiology·Natik PiriJoseph Caprioli
Dec 12, 2013·Journal of Neuroinflammation·Steven F AbcouwerDavid A Antonetti
Dec 18, 2013·Investigative Ophthalmology & Visual Science·Ronald Klein, Barbara E K Klein
Apr 27, 2016·Proceedings of the National Academy of Sciences of the United States of America·Elliott H SohnMichael David Abràmoff
Feb 1, 2017·Proceedings of the National Academy of Sciences of the United States of America·Erin-Mai F LimShalina S Ousman

❮ Previous
Next ❯

Citations

Mar 23, 2018·International Journal of Molecular Sciences·Anne RübsamPatrice E Fort
Jul 20, 2018·Investigative Ophthalmology & Visual Science·Maria VähätupaHannele Uusitalo-Järvinen
Aug 30, 2019·Allergy·Stanley J Szefler
Jul 3, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mikhail InyushinAstrid Zayas-Santiago
Jan 12, 2021·Progress in Retinal and Eye Research·Warren W PanPatrice E Fort
Sep 25, 2019·Experimental Eye Research·Sumaya HamadmadColleen M Cebulla
Jun 22, 2021·Journal of Diabetes Research·Shani PillarAndrzej Grzybowski
Jul 3, 2021·Antioxidants·Ashutosh S PhadtePatrice E Fort

❮ Previous
Next ❯

Datasets Mentioned

BETA
AB1662

Methods Mentioned

BETA
immunoprecipitation
transfection
protein folding
caspase
ELISA
Assay
PCR

Software Mentioned

InVivoVueTM DIVER
ImageJ
Skyline

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.