The interrelation of the angiotensin and endothelin systems on the modulation of NAD(P)H oxidaseThis paper is one of a selection of papers published in this Special issue, entitled Young Investigator's Forum.

2006 ◽  
Vol 84 (1) ◽  
pp. 21-28 ◽  
Author(s):  
Marc-André Laplante ◽  
Jacques de Champlain
Keyword(s):  
Superoxide Anion ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Cellular Membrane ◽  
Kinase C ◽  
Therapeutic Tools ◽  
Produce Superoxide Anion ◽  
Selection Of

The NAD(P)H oxidase is an enzyme assembled at the cellular membrane able to produce superoxide anion from NADH or NAD(P)H (nicotinamide adenine dinucleotide phosphate). It is one of the main sources of superoxide anion in cardiovascular tissues and its role in a variety of cardiovascular disorders such as atherosclerosis, cardiac hypertrophy, and endothelial dysfunction was recently proposed. Although, many factors and receptors were shown to lead to the activation of the enzyme, particulary the type 1 angiotensin receptor, the pathways involved are still widely unknown. Despite the identification of factors such as c-Src and protein kinase C implicated in the acute activation of NAD(P)H oxidase, the signalling involved in the sustained activation of the enzyme is probably far more complex than was previously envisioned. In this review, we describe the role of endothelin-1 in NAD(P)H oxidase signalling after a sustained stimulation by angiotensin II. Since most pathologies caused by an NAD(P)H oxidase overactivation develop over a relatively long period of time, it is necessary to better understand the long-term signalling of the enzyme for the development or use of more specific therapeutic tools.

The role of PKMζ in the maintenance of long-term memory: a review

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Hamish Patel ◽  
Reza Zamani
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Long Term Potentiation ◽  
Global Memory ◽  
Long Term Memory ◽  
Compensatory Mechanism ◽  
Term Memory ◽  
Kinase C

Abstract Long-term memories are thought to be stored in neurones and synapses that undergo physical changes, such as long-term potentiation (LTP), and these changes can be maintained for long periods of time. A candidate enzyme for the maintenance of LTP is protein kinase M zeta (PKMζ), a constitutively active protein kinase C isoform that is elevated during LTP and long-term memory maintenance. This paper reviews the evidence and controversies surrounding the role of PKMζ in the maintenance of long-term memory. PKMζ maintains synaptic potentiation by preventing AMPA receptor endocytosis and promoting stabilisation of dendritic spine growth. Inhibition of PKMζ, with zeta-inhibitory peptide (ZIP), can reverse LTP and impair established long-term memories. However, a deficit of memory retrieval cannot be ruled out. Furthermore, ZIP, and in high enough doses the control peptide scrambled ZIP, was recently shown to be neurotoxic, which may explain some of the effects of ZIP on memory impairment. PKMζ knockout mice show normal learning and memory. However, this is likely due to compensation by protein-kinase C iota/lambda (PKCι/λ), which is normally responsible for induction of LTP. It is not clear how, or if, this compensatory mechanism is activated under normal conditions. Future research should utilise inducible PKMζ knockdown in adult rodents to investigate whether PKMζ maintains memory in specific parts of the brain, or if it represents a global memory maintenance molecule. These insights may inform future therapeutic targets for disorders of memory loss.

Keratoprostheses in silicone oil-filled eyes: long-term outcomes

2018 ◽  
Vol 103 (6) ◽  
pp. 781-788 ◽  
Author(s):  
Geetha Iyer ◽  
Bhaskar Srinivasan ◽  
Shweta Agarwal ◽  
Ruchika Pattanaik ◽  
Ekta Rishi ◽  
...  
Keyword(s):  
Silicone Oil ◽  
Vitreoretinal Surgery ◽  
Retrospective Chart Review ◽  
Protective Role ◽  
Visual Rehabilitation ◽  
Two Factors

PurposeTo analyse the functional and anatomical outcomes of different types of keratoprostheses in eyes with retained silicone oil following vitreoretinal surgery.MethodsRetrospective chart review of patients operated with any type of permanent keratoprosthesis (Kpro) in silicone oil-filled eyes between March 2003 and June 2017 were analysed.Results40 silicone oil-filled eyes underwent keratoprostheses, of which 22 were type 1 and 18 were type 2 Kpros (Lucia variant—nine, modified osteo odonto kerato prosthesis (MOOKP)—four, Boston type 2—three and osteoKpro—two) with a mean follow-up of 61.54 , 42.77, 45.25 , 25 and 37 months, respectively. Anatomic retention of the primary Kpro was noted in 33 eyes (82.5%). A best-corrected visual acuity of better than 20/200 and 20/400 was achieved in 26 (65%)+32 (80%) eyes. Retroprosthetic membrane (RPM) was the most common complication noted in 17 eyes (42.5%). Perioptic graft melt was noted in 4 of 22 eyes of the type 1 Kpro (2 (10.5%) without associated ocular surface disorder (OSD)) and in 1 eye each of Boston and Lucia type 2 Kpro. Laminar resorption occurred in one eye each of the MOOKP and OKP groups. Endophthalmitis and glaucoma did not occur in any eye.ConclusionAppropriately chosen keratoprosthesis is a viable option for visual rehabilitation in eyes post vitreoretinal surgery with retained silicone oil-induced keratopathy not amenable to conventional penetrating keratoplasty. Kpro melt among type 1 Kpro did not occur in 89.5% eyes without associated OSD (19 of 22 eyes), despite the lack of aqueous humour and presence of RPM (4 eyes), two factors considered to play a significant role in the causation of sterile melts. Of interest to note was the absence of infection in any of these eyes. The possible protective role of oil from endophthalmitis is interesting, though yet to be ascertained.

scholarly journals Emerging Roles of Exosomes in T1DM

2020 ◽  
Vol 11 ◽  
Author(s):  
Haipeng Pang ◽  
Shuoming Luo ◽  
Yang Xiao ◽  
Ying Xia ◽  
Xia Li ◽  
...  
Keyword(s):  
Autoimmune Disorder ◽  
Elevated Blood Glucose Level ◽  
The Status ◽  
Life Threatening ◽  
Novel Biomarkers ◽  
Therapeutic Tools ◽  
Underlying Mechanisms ◽  
The Relationship

Type 1 diabetes mellitus (T1DM) is a complex autoimmune disorder that mainly affects children and adolescents. The elevated blood glucose level of patients with T1DM results from absolute insulin deficiency and leads to hyperglycemia and the development of life-threatening diabetic complications. Although great efforts have been made to elucidate the pathogenesis of this disease, the precise underlying mechanisms are still obscure. Emerging evidence indicates that small extracellular vesicles, namely, exosomes, take part in intercellular communication and regulate interorgan crosstalk. More importantly, many findings suggest that exosomes and their cargo are associated with the development of T1DM. Therefore, a deeper understanding of exosomes is beneficial for further elucidating the pathogenic process of T1DM. Exosomes are promising biomarkers for evaluating the risk of developingty T1DM, monitoring the disease state and predicting related complications because their number and composition can reflect the status of their parent cells. Additionally, since exosomes are natural carriers of functional proteins, RNA and DNA, they can be used as therapeutic tools to deliver these molecules and drugs. In this review, we briefly introduce the current understanding of exosomes. Next, we focus on the relationship between exosomes and T1DM from three perspectives, i.e., the pathogenic role of exosomes in T1DM, exosomes as novel biomarkers of T1DM and exosomes as therapeutic tools for T1DM.

scholarly journals The Role of Rho Kinase in Sex-Dependent Vascular Dysfunction in Type 1 Diabetes

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Daniel W. Nuno ◽  
Kathryn G. Lamping
Keyword(s):  
Kinase Inhibitors ◽  
Vascular Dysfunction ◽  
Rho Kinase ◽  
Term Treatment ◽  
Compensatory Mechanisms ◽  
Rho Kinase Inhibitors ◽  
Long Term Treatment

We hypothesized that rho/rho kinase plays a role in sex differences in vascular dysfunction of diabetics. Contractions to serotonin were greater in isolated aortic rings from nondiabetic males versus females and increased further in streptozotocin-induced diabetic males but not females. The increased contractions to serotonin in males were reduced by inhibitors of rho kinase (fasudil, Y27632 and H1152) despite no change in expression of rhoA or rho kinase. Contractions to U46619 were not altered by fasudil or Y27632 or the presence of diabetes. In contrast to acute effects of fasudil, chronic treatment with fasudil increased contractions to serotonin in aorta from both non-diabetic and diabetic males. In summary, serotonin-induced contractions were increased in aorta from diabetic males but not females. Although administration of rho kinase inhibitors acutely decreased contractions to serotonin, long-term treatment with fasudil increased contractions. Long-term fasudil treatment may increase compensatory mechanisms to enhance vasoconstrictions.

scholarly journals Influence of environmental colors and long-term sex isolation on zebrafish shoaling behavior

2019 ◽  
Vol 71 (2) ◽  
pp. 329-337
Author(s):  
Christian Lenzi ◽  
Chiara Grasso ◽  
Mircea Nicoara ◽  
Alexandra Savuca ◽  
Alin Ciobica ◽  
...  
Keyword(s):  
Social Interactions ◽  
Potential Influence ◽  
Male Fish ◽  
Male And Female ◽  
Shoaling Behavior ◽  
Males And Females ◽  
Complex Social Behavior ◽  
Selection Of

Zebrafish has a complex social behavior and little is known about the role of sexual preference and their environmental social interactions. In this study we investigated the potential influence of environmental colors and shoaling preferences of zebrafish male and female populations, with a focus on visual communication. Males and females were kept for 7 days in gender-isolated tanks, with a specific habitat color for each group: green for males and red for females. After the pre-test period, all the animals were kept separated and 8 noninvasive behavioral tests were conducted in a T-maze, with the application of different visual stimuli. We did not observe any clear influence of environmental coloring on social zebrafish choices. Significant sex-related differences were found in shoaling partner preference (i.e. same sex vs. other sex, one fish vs. three fish) as follows: females showed a tendency to avoid other females and spent more time with males. Male fish did not display a preference between one or three fish stimuli and they shoaled more with another male and less with a potential sexual partner. There was an obvious difference between males and females in responses and selection of shoaling partners.

scholarly journals The Role of the Gut Microbiota in the Pathogenesis of Diabetes

2022 ◽  
Vol 23 (1) ◽  
pp. 480
Author(s):  
Weronika Bielka ◽  
Agnieszka Przezak ◽  
Andrzej Pawlik
Keyword(s):  
Gut Microbiota ◽  
Cell Function ◽  
Bacterial Composition ◽  
New Developments ◽  
Β Cell Function ◽  
Therapeutic Problem

Diabetes mellitus is a significant clinical and therapeutic problem because it can lead to serious long-term complications. Its pathogenesis is not fully understood, but there are indications that dysbiosis can play a role in the development of diabetes, or that it appears during the course of the disease. Changes in microbiota composition are observed in both type 1 diabetes (T1D) and type 2 diabetes (T2D) patients. These modifications are associated with pro-inflammation, increased intestinal permeability, endotoxemia, impaired β-cell function and development of insulin resistance. This review summarizes the role of the gut microbiota in healthy individuals and the changes in bacterial composition that can be associated with T1D or T2D. It also presents new developments in diabetes therapy based on influencing the gut microbiota as a promising method to alter the course of diabetes. Moreover, it highlights the lacking data and suggests future directions needed to prove the causal relationship between dysbiosis and diabetes, both T1D and T2D.

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