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Renal Disease; Fluid and Electrolyte Disorders
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
The clinical presentation of CKD varies from asymptomatic detection of biochemical abnormalities on blood tests taken for some other reason to symptomatic advanced CKD with the uraemic syndrome. The uraemic syndrome can cause confusion, tremor, itch, anaemia, anorexia and pericarditis. CKD can present with features of an underlying disease such as PKD, glomerulonephritis or diabetes mellitus.
The Role of Epigenetics in Skeletal Muscle Adaptations to Exercise and Exercise Training
Published in Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse, The Routledge Handbook on Biochemistry of Exercise, 2020
Emerging evidence suggests that histone modifications could also be an important epigenetic mechanism contributing to exercise-induced transcriptional responses in skeletal muscle. Global histone 3 acetylation at lysine 36 is increased immediately following 60 min of cycling in human skeletal muscle and is associated with the nuclear export of the class IIa histone deacetylases (HDACs) (41). This sub-family of HDACs does not possess activity against acetylated lysine, but acts as scaffolds to recruit transcriptional co-repressors and other HDAC isoforms to specific transcription factors (18), such as MEF2 (45). The phosphorylation-dependent nuclear export of the class IIa HDACs disrupts this transcriptional co-repressor complex, resulting in transcription factor–specific gene expression responses (45). The importance of disrupting this co-repressor complex for the transcriptional response to exercise has been highlighted in a recent study (19). Skeletal muscle expression of HDAC4 and HDAC5 mutants that have impaired recruitment of the co-repressor complex results in an exercise-like transcriptional response and enhanced capacity for lipid oxidation (19). Phosphorylation of the class IIa HDACs appears to be regulated by a number of kinases, including the AMP-activated protein kinase (AMPK) (44), the calcium/calmodulin-dependent protein kinase II (CaMKII), and protein kinase D (PKD) (12), in a redundant fashion (43). These studies delineate important signalling pathways by which exercise can induce specific transcriptional responses through epigenetic mechanisms.
Renal Pathophysiology
Published in Manit Arya, Taimur T. Shah, Jas S. Kalsi, Herman S. Fernando, Iqbal S. Shergill, Asif Muneer, Hashim U. Ahmed, MCQs for the FRCS(Urol) and Postgraduate Urology Examinations, 2020
Herman S. Fernando, Mohamed Yehia Abdallah, Iqbal S. Shergill
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cystic kidney diseases with an incidence of 1–2:1,000 live births. About 10% of end-stage renal disease (ESRD) patients being treated with hemodialysis were originally diagnosed as ADPKD. There are three genetic mutations in the PKD-1, PKD-2, and PKD3 gene with similar phenotypical presentations. Gene PKD-1 is located on chromosome 16 and codes for a protein involved in the regulation of cell cycle and intracellular calcium transport in epithelial cells, and is responsible for 85% of the cases of ADPKD. A group of voltage-linked calcium channels are coded for by PKD-2 on chromosome 4. The incidence of autosomal recessive polycystic kidney disease (ARPKD) is 1:20,000 live births and is typically identified in the first few weeks after birth. Unfortunately, resulting hypoplasia results in a 30% death rate in neonates with ARPKD.
Research progress on related mechanisms of uric acid activating NLRP3 inflammasome in chronic kidney disease
Published in Renal Failure, 2022
Miao Wang, Xin Lin, Xiaoming Yang, Yanlang Yang
In recent years, the role of the Golgi apparatus in the activation of NLRP3 inflammasomes has gradually been recognized. The Golgi body contains many different enzymes, including glycosyltransferase, oxidoreductase, phosphatase, and protein kinase, which provide conditions for the activation and assembly of the NLRP3 inflammasome. In a recent study, brefeldin A disrupted Golgi integrity and reduced caspase-1 activation, IL-1β secretion and ASC spot formation after NLRP3 inflammasome activation [30], suggesting that Golgi activation and NLRP3 activation are closely related. NLRP3 is recruited to the endoplasmic reticulum membrane associated with mitochondria (MAM) and is activated by MAM-derived effectors. MAM is located near the Golgi membrane. After stress, the diacylglycerol (DAG) level in the Golgi apparatus increases rapidly, recruiting the key effector protein of DAG, protein kinase D (PKD). The phosphorylation of NLRP3 by PKD on the Golgi apparatus is sufficient to release NLRP3 from MAM, leading to the assembly of active inflammasomes [31].High concentrations of uric acid or uric acid crystals activate NLRP3 inflammasomes and can cause intracellular oxidative stress and endoplasmic reticulum dysfunction. However, few studies have investigated whether uric acid can change the recruitment, assembly and displacement of NLRP3 inflammasomes by affecting changes in the endoplasmic reticulum-Golgi cell inner membrane system.
Advances in understanding the role of angiotensin-regulated proteins in kidney diseases
Published in Expert Review of Proteomics, 2019
Ana Belén Sanz, Adrian Mario Ramos, Maria Jose Soler, Maria Dolores Sanchez-Niño, Beatriz Fernandez-Fernandez, Maria Vanessa Perez-Gomez, Marta Ruiz Ortega, Gloria Alvarez-Llamas, Alberto Ortiz
Phosphorylation is a key posttranslational modification involved in protein activation or loss of function induced by angiotensin II and derivated peptides. Quantitative stable isotope labeling of amino acids was used to explore the phosphoproteome of the AT1R signaling network in cultured human embryonic kidney cells stimulated with angiotensin II or the biased agonist SII-angiotensin II [11]. Over 1150 phosphorylation sites were regulated by angiotensin II or SII-angiotensin II, but only 36% of the AT1R-regulated phosphorylations were regulated by SII-angiotensin II. The pattern of protein kinases activated by G angiotensin II or SII-angiotensin II differed, but protein kinase D (PRKD1) was a key protein regulator of AT1R signaling activated by both peptides [11]. PRKD1 had been previously implicated in aldosterone regulation of sodium transporters, intracellular angiotensin II signaling, and pathological cardiovascular remodeling and recent proteomics analysis identified it as a downstream signaling molecule for MasR [89]. Integration of prior phosphoproteomics data identified AT1R-dependent activation of 48 of the 285 kinases detected in HEK293 cells, including Aurora B, CLK3, and PKG1 on top of better known targets such as PKA, PKB, and PKC, thus expanding the range of known kinases activated by angiotensin II [90].
The role of radiation induced oxidative stress as a regulator of radio-adaptive responses
Published in International Journal of Radiation Biology, 2020
Mohsen Sisakht, Maryam Darabian, Amir Mahmoodzadeh, Ali Bazi, Sayed Mohammad Shafiee, Pooneh Mokarram, Zahra Khoshdel
NF-κB is known as a redox-sensitive, anti-apoptotic transcription factor (Anandhan et al. 2015). In normal conditions, NF-κB binds to its inhibitor and remains in the cytosol (Moscat et al. 2016). It was reported that H2O2 can activate NF-κB (Gloire et al. 2006) in T-cells through induction of either IκB kinase (IKK) or PKD (Storz et al. 2004). Activated NF-κB is then translocated into the nucleus and increases the expression of the genes involved in the cell survival and autophagy (i.e., Beclin 1/ATG6 or SQSTM1/p62 (Figure 2(C)) (Ishaq et al. 2014).