Diabetic cataract formation: potential role of glycosylation of lens crystallins.

AbstractDiabetic cataracts can occur at an early age, causing visual impairment or blindness. The detailed molecular mechanisms of diabetic cataract formation remain incompletely understood, and there is no well-documented prophylactic agent. Galactose-fed rats and ex vivo treatment of lenses with galactose are used as models of diabetic cataract. To assess the role of histone acetyltransferases, we conducted cataract prevention screening with known histone acetyltransferase (HAT) inhibitors. Ex vivo treatment with a HAT inhibitor strongly inhibited the formation of lens turbidity in high-galactose conditions, while addition of a histone deacetylase (HDAC) inhibitor aggravated turbidity. We conducted a microarray to identify genes differentially regulated by HATs and HDACs, leading to discovery of a novel cataract causative factor, Plk3. Plk3 mRNA levels correlated with the degree of turbidity, and Plk3 inhibition alleviated galactose-induced cataract formation. These findings indicate that epigenetically controlled Plk3 influences cataract formation. Our results demonstrate a novel approach for prevention of diabetic cataract using HAT and Plk3 inhibitors.

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Senescence increases vascular smooth muscle proliferation and exacerbates neointimal formation: Potential role of miR-21 and Akt/mTOR mediated signaling pathways

Atherosclerosis ◽

10.1016/j.atherosclerosis.2015.04.273 ◽

2015 ◽

Vol 241 (1) ◽

pp. e78

Author(s):

M. Garabito ◽

M. Roque ◽

S. Novella ◽

C. Hermenegildo ◽

A. Dantas

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Signaling Pathways ◽

Potential Role ◽

Neointimal Formation ◽

Formation Potential ◽

Smooth Muscle Proliferation

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Cataract in the human lens: a systematic review of proteomic studies

10.1101/19009035 ◽

2019 ◽

Author(s):

Christina Karakosta ◽

Argyrios Tzamalis ◽

Michalis Aivaliotis ◽

Ioannis Tsinopoulos

Keyword(s):

Systematic Review ◽

Oxidant Stress ◽

Critical Role ◽

Human Lens ◽

Cataract Formation ◽

Post Translational Modification ◽

Lens Crystallins ◽

Ability To Act ◽

Age Related

AbstractBackground/AimThe aim of this systematic review is to identify all the available data on human lens proteomics with a critical role to age-related cataract formation in order to elucidate the physiopathology of the aging lens.MethodsWe searched on Medline and Cochrane databases. The search generated 328 manuscripts. We included nine original proteomic studies that investigated human cataractous lenses.ResultsDeamidation was the major age-related post-translational modification. There was a significant increase in the amount of αA-crystallin D-isoAsp58 present at all ages, while an increase in the extent of Trp oxidation was apparent in cataract lenses when compared to aged normal lenses. During aging, enzymes with oxidized cysteine at critical sites included GAPDH, glutathione synthase, aldehyde dehydrogenase, sorbitol dehydrogenase, and PARK7.ConclusionD-isoAsp in αA crystallin could be associated with the development of age-related cataract in human, by contributing to the denaturation of a crystallin, and decreasing its ability to act as a chaperone. Oxidation of Trp may be associated with nuclear cataract formation in man, while the role of oxidant stress in age-related cataract formation is dominant.SynopsisThe oxidative stress and the post-translational modification of deamidation in lens crystallins seem to play a significant role in the formation of age-related cataract in human.

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POPDC proteins and cardiac function

Biochemical Society Transactions ◽

10.1042/bst20190249 ◽

2019 ◽

Vol 47 (5) ◽

pp. 1393-1404 ◽

Cited By ~ 4

Author(s):

Thomas Brand

Keyword(s):

Potential Role ◽

Striated Muscle ◽

Short Review ◽

Effector Proteins ◽

Muscle Disease ◽

Disease Genes ◽

Protein Protein Interaction ◽

Interaction Partners ◽

And Function

Abstract The Popeye domain-containing gene family encodes a novel class of cAMP effector proteins in striated muscle tissue. In this short review, we first introduce the protein family and discuss their structure and function with an emphasis on their role in cyclic AMP signalling. Another focus of this review is the recently discovered role of POPDC genes as striated muscle disease genes, which have been associated with cardiac arrhythmia and muscular dystrophy. The pathological phenotypes observed in patients will be compared with phenotypes present in null and knockin mutations in zebrafish and mouse. A number of protein–protein interaction partners have been discovered and the potential role of POPDC proteins to control the subcellular localization and function of these interacting proteins will be discussed. Finally, we outline several areas, where research is urgently needed.

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