China
Africa
Explore chapters and articles related to this topic
Cardiac Hypertrophy, Heart Failure and Cardiomyopathy
Published in Mary N. Sheppard, Practical Cardiovascular Pathology, 2022
These diseases lead to cardiac hypertrophy and include Pompe's disease. Myocyte vacuoles containing glycogen or intermediary metabolites occur (Fig. 5.79). The glycogen is brightly periodic-acid Schiff (PAS) positive. The heart often enlarges with a thick-walled asymmetric left ventricle. Other genetic causes of cardiac hypertrophy include mutations in PRKAG2, the regulatory γ subunit of AMP-activated protein kinase. PRKAG2 mutations cause myocyte hypertrophy by stimulating glycogen-filled vacuoles but cause neither myocyte disarray nor interstitial fibrosis, which typically occur with defects of sarcomere-protein genes. Danon disease (an X-linked lysosome-associated membrane protein [LAMP2] deficiency) and Fabry's give a similar appearance both macroscopically and microscopically. Cardiomyopathy due to PRKAG2 mutations with progressive conduction-system disease may necessitate the implantation of a pacemaker but has a good long-term prognosis. By contrast, the prognosis associated with cardiomyopathy due to LAMP2 mutations is poor with onset of disease during adolescence, followed by a rapid progression towards end-stage HF early in adulthood.
Genetics and Genetic Testing in Hypertrophic Cardiomyopathy
Published in Srilakshmi M. Adhyapak, V. Rao Parachuri, Hypertrophic Cardiomyopathy, 2020
The pre-test probability of detecting these HCM phenocopies is governed by the presence of certain clinical red flags encountered during the work-up of these patients. These red flags may include Wolff–Parkinson–White pattern in PRKAG2 and Danon disease, greatly increased precordial voltages, and massive LVH in patients with LAMP2 mutations (Danon disease) [25, 27] and symmetric LVH with late gadolinium enhancement of the posterobasal LV seen in Fabry disease [28, 29].
Endolysosomal Patch Clamping
Published in Bruno Gasnier, Michael X. Zhu, Ion and Molecule Transport in Lysosomes, 2020
Cheng-Chang Chen, Christian Grimm, Christian Wahl-Schott, Martin Biel
Additionally, the incubation of cells with sucrose (50 mM) for 8–12 hours has been applied to enlarge LAMP1-positive lysosomal vacuoles for whole-lysosome patch clamping. Sucrose is taken up by cells through endocytosis but not degraded within the vacuoles, resulting in its accumulation inside vacuoles and osmotic swelling of the LAMP1- and LAMP2-positive lysosomes (DeCourcy and Storrie, 1991). The median diameter of the enlarged vacuoles can reach 1.3 µm (Bandyopadhyay et al., 2014). In a recent study, Ca2+-activated K+ outward currents through BK channels located on endolysosomal membranes of COS-1 cells have been measured by enlarging the vacuoles using a low concentration of sucrose (Wang et al., 2017).
IFN-γ-induced ER stress impairs autophagy and triggers apoptosis in lung cancer cells
Published in OncoImmunology, 2021
Can Fang, Tao Weng, Shaojie Hu, Zhiwei Yuan, Hui Xiong, Bing Huang, Yixin Cai, Lequn Li, Xiangning Fu
LysoTracker is used to detect lysosomes in living cells.40 LysoTracker Red DND-99 was used to evaluate lysosomes in cells treated with IFN-γ. The immunoreactivity of LysoTracker was significantly reduced in cells treated with IFN-γ compared to untreated cells, similar to the cells cultured with Baf A1 (Figure 5a). Lysosomal membranes contain several highly N-glycosylated proteins, among which LAMP-1 and LAMP-2 are the best known.41 LAMP-1 and LAMP-2 play essential roles in autophagosome maturation. As shown in Figure 5b, LAMP-1 and LAMP-2 expression decreased in cells cultured with IFN-γ on day 3. IFN-γ did not affect LAMP expression in UMC-11 cells. To confirm the western blot analysis results, we used cell immunofluorescence to detect LAMP-1. The immunoreactivity of LAMP-1 reduced significantly in cells treated with IFN-γ compared to untreated cells (Figure 5c). Notably, IFN-γ did not reduce the transcription of LAMP1 and LAMP2 (Figure S4).
HSC70 expression is reduced in lymphomonocytes of sporadic ALS patients and contributes to TDP-43 accumulation
Published in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 2020
Alessandro Arosio, Riccardo Cristofani, Orietta Pansarasa, Valeria Crippa, Chiara Riva, Riccardo Sirtori, Virginia Rodriguez-Menendez, Nilo Riva, Francesca Gerardi, Christian Lunetta, Cristina Cereda, Angelo Poletti, Carlo Ferrarese, Lucio Tremolizzo, Gessica Sala
The two main effectors of CMA, HSC70, and LAMP2A were considered and their mRNA and protein levels assessed in PBMCs. A significant reduction of mRNA (−28%, p < 0.001) and protein (−30%, p < 0.01) levels of HSC70 was evidenced in cells from ALS patients with respect to controls (Figure 5(A–C)). No change was observed in LAMP2A expression between patients and control subjects (Figure 5(D–F)). However, a negative correlation between LAMP2A protein levels and disease duration emerged in sALS patients (r = −0.52; p < 0.05) (as shown in Supplementary Figure S1A). Dichotomizing patients according to disease duration (median value 18 months), we evidenced that those patients with a shorter disease duration are characterized by LAMP2A protein levels similar to controls, while those with longer disease duration showed reduced LAMP2A protein levels (−53%, p < 0.05) (as shown in Supplementary Figure S1B). Conversely, no effect of disease duration emerged on HSC70 reduction in patient PBMCs (data not shown). No additional correlation was found among LAMP2A or HSC70 and other clinical parameters (data not shown).
Danon disease presenting with early onset of hypertrophic cardiomyopathy and peripheral pigmentary retinal dystrophy in a female with a de novo novel mosaic mutation in the LAMP2 gene
Published in Ophthalmic Genetics, 2019
Monika Meinert, Elisabet Englund, Carola Hedberg-Oldfors, Anders Oldfors, Björn Kornhall, Catarina Lundin, Elisabeth Wittström
The young female Danon disease patient described in this study presented with early hypertrophic cardiomyopathy, depression and anxiety, and PPRD without any reported visual problems. Danon disease is a multisystemic disorder, often involving several organs, as has been reported both in patients with Danon disease and in lamp2 knockout mice (1,22,23). Danon disease patients with genetically confirmed LAMP2 variants exhibit LAMP2 protein deficiency in many organs, including the cardiac and skeletal muscles, leukocytes and fibroblasts, and, like lamp2 knockout mice, these patients showed involvement of various organs including the liver, lung, and brain. However, these patients also exhibited gastrointestinal, renal and ocular symptoms, as well as intellectual disability and psychiatric disorders such as depression and anxiety (23,24).