bims-aucach Biomed News
on Autophagy and cachexia
Issue of 2022‒03‒06
ten papers selected by
Kleiton Silva
Rowan University
  1. Perceptions and Experiences of a Progressive Resistance Exercise Program in People with Chronic Kidney Disease.
  2. Mitochondrial-apoptotic signaling involvement in remodeling during myogenesis and skeletal muscle atrophy.
  3. Long-Term Habitual Exercise and Combination of β-Hydroxy-β-Methylbutyrate plus Black Ginger Alter the Autophagy and Mitochondria Related Genes in SAMP8 Mice.
  4. Multisystem derangements in frailty and sarcopenia: a source for biomarker discovery.
  5. Long-lived mitochondrial proteins and why they exist.
  6. Current Status of Autophagy Enhancers in Metabolic Disorders and Other Diseases.
  7. Frailty as an Independent Risk Factor for Depression in Patients With End-Stage Renal Disease: A Cross-Sectional Study.
  8. Exercise and Oxidative Stress Biomarkers among Adult with Cancer: A Systematic Review.
  9. Isolation of Mitochondria from Mouse Skeletal Muscle for Respirometric Assays.
  10. PI3K inhibitor 3-MA promotes the antiproliferative activity of esomeprazole in gastric cancer cells by downregulating EGFR via the PI3K/FOXO3a pathway.
  1. Nephrol Nurs J. 2022 Jan-Feb;49(1):49(1): 19-27
    Perceptions and Experiences of a Progressive Resistance Exercise Program in People with Chronic Kidney Disease.
    Courtney J Lightfoot, Noemi Vadaszy, Emma L Watson, Noelle Robertson, Alice C Smith.
      Muscle wasting is highly prevalent in chronic conditions, such as chronic kidney disease (CKD), and can result in decreased physical functioning and strength, and impaired ability to perform daily tasks, thus impacting quality of life. Exercise, particularly resistance training, promotes a multitude of benefits, including prevention and management of muscle dysfunction; however, engagement in resistance training is poor. The aim of this study was to understand the views of people with CKD who participated in a research study evaluating a progressive resistance exercise program. Semi-structured interviews were conducted with 11 people with CKD Stage 3 and 4. Five themes were identified: experiences of muscle weakness; preconceptions of resistance exercise; experiences of participating in a resistance exercise program; perceived impact of the resistance exercise program; and maintenance of resistance exercise. Parti - cipants believed the resistance exercise program could improve their functional performance and quality of life. They disclosed factors that can enable or deter both uptake and maintenance in training, which can be considered when developing resistance-based exercise programs. Findings highlight the need for patient education and counselling about the importance and implementation of appropriate and progressive resistance exercise training.
    Keywords:  chronic kidney disease; patient experience; patient perspective; resistance exercise; resistance training
  2. Semin Cell Dev Biol. 2022 Feb 28. pii: S1084-9521(22)00039-8. [Epub ahead of print]
    Mitochondrial-apoptotic signaling involvement in remodeling during myogenesis and skeletal muscle atrophy.
    Fasih Ahmad Rahman, Joe Quadrilatero.
      Mitochondria play a major role in apoptotic signaling. In addition to its role in eliminating dysfunctional cells, mitochondrial apoptotic signaling is implicated as a key component of myogenic differentiation and skeletal muscle atrophy. For example, the activation of cysteine-aspartic proteases (caspases; CASP's) can aid in the initial remodeling stages of myogenic differentiation by cleaving protein kinases, transcription factors, and cytoskeletal proteins. Precise regulation of these signals is needed to prevent excessive cell disassemble and subsequent cell death. During skeletal muscle atrophy, the activation of CASP's and mitochondrial derived nucleases participate in myonuclear fragmentation, a potential loss of myonuclei, and cleavage of contractile structures within skeletal muscle. The B cell leukemia/lymphoma 2 (BCL2) family of proteins play a significant role in regulating myogenesis and skeletal muscle atrophy by governing the initiating steps of mitochondrial apoptotic signaling. This review discusses the role of mitochondrial apoptotic signaling in skeletal muscle remodeling during myogenic differentiation and skeletal muscle pathological states, including aging, disuse, and muscular dystrophy.
    Keywords:  Aging; Apoptosis; Atrophy; BCL2; CASP9; Disease; Disuse; Mitochondria; Muscular dystrophy; Myogenesis; Skeletal muscle
    DOI:  https://doi.org/10.1016/j.semcdb.2022.01.011
  3. J Nutr Sci Vitaminol (Tokyo). 2022 ;68(1): 39-46
    Long-Term Habitual Exercise and Combination of β-Hydroxy-β-Methylbutyrate plus Black Ginger Alter the Autophagy and Mitochondria Related Genes in SAMP8 Mice.
    Kai Aoki, Masaki Konno, Katsuyuki Tokinoya, Katsunari Honda, Takuya Abe, Takeshi Nagata, Masaaki Takehara, Takehito Sugasawa, Kazuhiro Takekoshi, Hajime Ohmori.
      Muscle mass and strength decrease with aging; however, habitual exercise can maintain muscle health. β-Hydroxy-β-methyl butyrate calcium (HMB) and black ginger (BG) improve muscle protein metabolism and energy production. Combining these two molecules, which have similar effects, may have a synergistic effect. Senescence-accelerated mouse-prone 8 (SAMP8) is a useful model of muscle aging. Therefore, we explored how the combination of habitual exercise, HMB, and BG affected muscle aging. We used 28-wk-old (28w) SAMP8 mice divided into six groups: 28 wk (28w), 44 wk (44w, Con), exercise (Ex), Ex+BG, Ex+HMB, and Ex+BG+HMB (Ex+Comb). Mice were required to run on a treadmill for 16 wk for 5 d per week. In 28w and 44w mice, grip strength tests and dissection were conducted. Muscle weight was measured, and qPCR and immunoblotting were conducted. Muscle mass and strength were declined in the 44w group. Exercise with HMB or BG alone had no effect, whereas muscle mass and strength were augmented in the Ex+Comb group. Similarly, levels of mitochondrial function- and biogenesis-related genes were increased. Autophagy-related protein (Atg3, 7, 16L1 and Beclin1) were altered in the Ex+Comb group. These results suggest that Ex+Comb affects autophagy. Overall, the combination of habitual exercise and HMB+BG may enhance muscle mass and strength by affecting the mitochondrial and autophagy systems in SAMP8.
    Keywords:  HMBCa; SAMP8; black ginger; exercise; sarcopenia
    DOI:  https://doi.org/10.3177/jnsv.68.39
  4. Curr Opin Clin Nutr Metab Care. 2022 Mar 02.
    Multisystem derangements in frailty and sarcopenia: a source for biomarker discovery.
    Anna Picca, Riccardo Calvani, Emanuele Marzetti.
      PURPOSE OF REVIEW: Multisystem derangements, encompassing metabolic, musculoskeletal and stress-response systems, occur during aging and are associated with the development of physical frailty and sarcopenia. These modular changes are relevant sources for the identification of biomarkers for the two conditions. Here, we provide an up-to-date overview on existing biomarkers of physical frailty and sarcopenia and discuss emerging approaches for biomarker discovery.RECENT FINDINGS: Inflammatory, metabolic and hematologic markers are shared between physical frailty and sarcopenia. Gut microbial derivatives and damage-associated molecular patterns transferred via extracellular vesicles have been indicated as possible gut-muscle axis regulators and candidate markers of physical frailty and sarcopenia.
    SUMMARY: Mediators of metabolic, musculoskeletal and stress-response system dysregulation are shared by physical frailty and sarcopenia and indicate the existence of common pathophysiological pathways. Multiplatform biomarker analyses have been proposed as an innovating approach for tracking the multifaceted and dynamic nature of physical frailty and sarcopenia. Upon validation, the identified biomarkers may support diagnostic makeup and tracking of the two conditions in both research and clinical settings.
    DOI:  https://doi.org/10.1097/MCO.0000000000000828
  5. Trends Cell Biol. 2022 Feb 24. pii: S0962-8924(22)00034-4. [Epub ahead of print]
    Long-lived mitochondrial proteins and why they exist.
    Ewa Bomba-Warczak, Jeffrey N Savas.
      Intracellular long-lived proteins (LLPs) provide structural support for several highly stable protein complexes and assemblies that play essential roles in ensuring cellular homeostasis and function. Recently, mitochondrial long-lived proteins (mt-LLPs) were discovered within inner mitochondria membranes (IMMs) and cristae invagination in tissues with old postmitotic cells. This observation is at odds with the fact that mitochondria are highly dynamic organelles that are continually remodeled through processes of fission, fusion, biogenesis, and multiple quality control pathways. In this opinion article, we propose that a subset of the mitochondrial proteome persists over long time frames and these mt-LLPs provide key structural support for the lifelong maintenance of mitochondrial structure.
    Keywords:  cristae ultrastructure; long-lived proteins; mitochondria; mitochondrial dynamics; protein turnover; stable structures
    DOI:  https://doi.org/10.1016/j.tcb.2022.02.001
  6. Front Cell Dev Biol. 2022 ;10 811701
    Current Status of Autophagy Enhancers in Metabolic Disorders and Other Diseases.
    Kihyoun Park, Myung-Shik Lee.
      Autophagy is pivotal in the maintenance of organelle function and intracellular nutrient balance. Besides the role of autophagy in the homeostasis and physiology of the individual tissues and whole organism in vivo, dysregulated autophagy has been incriminated in the pathogenesis of a variety of diseases including metabolic diseases, neurodegenerative diseases, cardiovascular diseases, inflammatory or immunological disorders, cancer and aging. Search for autophagy modulators has been widely conducted to amend dysregulation of autophagy or pharmacologically modulate autophagy in those diseases. Current data support the view that autophagy modulation could be a new modality for treatment of metabolic syndrome associated with lipid overload, human-type diabetes characterized by deposition of islet amyloid or other diseases including neurodegenerative diseases, infection and cardiovascular diseases. While clinically available bona fide autophagy modulators have not been developed yet, it is expected that on-going investigation will lead to the development of authentic autophagy modulators that can be safely administered to patients in the near future and will open a new horizon for treatment of incurable or difficult diseases.
    Keywords:  autophagy; endoplasmic reticulum; lysosome; metabolic diseases; mitochondria; modulator
    DOI:  https://doi.org/10.3389/fcell.2022.811701
  7. Front Med (Lausanne). 2022 ;9 799544
    Frailty as an Independent Risk Factor for Depression in Patients With End-Stage Renal Disease: A Cross-Sectional Study.
    Chun-Yi Chi, Szu-Ying Lee, Chia-Ter Chao, Jenq-Wen Huang.
      Background: Depression confers substantial disease burden globally, especially among those with chronic kidney disease (CKD). The presence of depression significantly impairs one's quality of life. Risk factors for depression in patients with CKD remain under-appreciated, and whether frailty, a geriatric phenotype, constitutes a risk factor for depression in this population is unknown.Methods: We prospectively enrolled patients with end-stage renal disease (ESRD) undergoing hemodialysis for >3 months from National Taiwan University Hospital Yunlin Branch between 2019 and 2021. Clinical, physical, functional, and performance parameters were recorded, followed by frailty/sarcopenia assessment. Depression was screened for using the Geriatric Depression Scale. We analyzed the independent relationship between frailty and depression in these patients, using multiple regression analyses.
    Results: Totally 151 patients with ESRD were enrolled (mean 61.1 years, 66.9% male), among whom 16.6% had screening-identified depression. ESRD participants with depression did not differ from those without regarding most parameters except serum creatinine, functional indices, and sarcopenia/frailty status. We found that having greater frail severities was independently associated with a higher probability of depression; having FRAIL- (odds ratio [OR] 5.418) and SOF-based (OR 2.858) frailty independently correlated with a higher depression probability. A linear relation exists between a greater frail severity and the probability of depression. Using a more relaxed criterion for detecting depression, higher SOF scores remained significantly associated with an increased depression risk.
    Conclusions: In patients with CKD, frailty independently correlated with a higher probability of having depression. Strategies aiming to attenuate frailty may be able to benefit those with depression simultaneously in this population.
    Keywords:  chronic kidney disease; depression; end-stage renal disease; frailty; geriatric phenotype; malnutrition; sarcopenia
    DOI:  https://doi.org/10.3389/fmed.2022.799544
  8. Oxid Med Cell Longev. 2022 ;2022 2097318
    Exercise and Oxidative Stress Biomarkers among Adult with Cancer: A Systematic Review.
    Yari Longobucco, Alice Masini, Sofia Marini, Giuseppe Barone, Carmela Fimognari, Laura Bragonzoni, Laura Dallolio, Francesca Maffei.
      Evidence shows that exercise can have a favourable effect in cancer patients. The exercise's clinical benefits are likely to concern multiple interrelated biological pathways, among which oxidative stress plays a key role. Regular training can induce an adaptive response that strengthens the antioxidative status of the body. To formulate public health recommendations regarding the optimal exercise prescription for cancer patients, a detailed understanding is needed regarding the effect of exercise on variables linked to oxidative stress and antioxidant status of patients. The goal of this systematic review, based on PRISMA, was to explore and critically analyse the evidence regarding the efficacy of exercise on oxidative stress biomarkers among people with cancer. Study search was conducted in the following databases: PubMed, Cochrane, CINAHL, Embase, PEDro, and SPORTDiscus. The studies' quality was assessed with the Cochrane risk-of-bias tool and STROBE scale. After identification and screening steps, 10 articles were included. The findings provide an encouraging picture of exercise, including resistance training and aerobic activities, in people with cancer. The exercise improved the indicators of the total antioxidant capacity, increased the antioxidant enzymes' activity, or reduced the biomarkers of oxidative damage in various forms of cancer such as breast, lung, head, and neck. Regarding oxidative DNA damage, the role of exercise intervention has been difficult to assess. The heterogeneity of study design and the plethora of biomarkers measured hampered the comparison of the articles. This limited the possibility of establishing a comprehensive conclusion on the sensitivity of biomarkers to estimate the exercise's benefits. Further high-quality studies are required to provide data regarding oxidative stress biomarkers responding to exercise. This information will be useful to assess the efficacy of exercise in people with cancer and support the appropriate prescription of exercise in anticancer strategy.
    DOI:  https://doi.org/10.1155/2022/2097318
  9. J Vis Exp. 2022 Feb 10.
    Isolation of Mitochondria from Mouse Skeletal Muscle for Respirometric Assays.
    Juan Diego Hernández-Camacho, Cristina Vicente-García, Ana Sánchez-Cuesta, Daniel J M Fernandez-Ayala, Jaime J Carvajal, Plácido Navas.
      Most of the cell's energy is obtained through the degradation of glucose, fatty acids, and amino acids by different pathways that converge on the mitochondrial oxidative phosphorylation (OXPHOS) system, which is regulated in response to cellular demands. The lipid molecule Coenzyme Q (CoQ) is essential in this process by transferring electrons to complex III in the electron transport chain (ETC) through constant oxidation/reduction cycles. Mitochondria status and, ultimately, cellular health can be assessed by measuring ETC oxygen consumption using respirometric assays. These studies are typically performed in established or primary cell lines that have been cultured for several days. In both cases, the respiration parameters obtained may have deviated from normal physiological conditions in any given organ or tissue. Additionally, the intrinsic characteristics of cultured single fibers isolated from skeletal muscle impede this type of analysis. This paper presents an updated and detailed protocol for the analysis of respiration in freshly isolated mitochondria from mouse skeletal muscle. We also provide solutions to potential problems that could arise at any step of the process. The method presented here could be applied to compare oxygen consumption rates in diverse transgenic mouse models and study the mitochondrial response to drug treatments or other factors such as aging or sex. This is a feasible method to respond to crucial questions about mitochondrial bioenergetics metabolism and regulation.
    DOI:  https://doi.org/10.3791/63336
  10. Biomed Pharmacother. 2022 Feb 26. pii: S0753-3322(22)00053-1. [Epub ahead of print]148 112665
    PI3K inhibitor 3-MA promotes the antiproliferative activity of esomeprazole in gastric cancer cells by downregulating EGFR via the PI3K/FOXO3a pathway.
    Jinfeng Du, Qian Xu, Han Zhao, Xiyun Jia, Nan Ba, Fanghui Peng, Zisen Zhang.
      Gastric cancer is a common gastrointestinal malignancy worldwide, with a high mortality rate and poor prognosis. Esomeprazole (ESO) has been shown to have anticancer activity by affecting cell growth and autophagy and its mechanism in gastric cancer cells is evident. The PI3K/AKT/FOXO3a pathway is central in cancers. 3-Methyladenine (3-MA), a dual inhibitor of PI3K and autophagy, plays a synergistic role in combination with antitumor agents. In this study, we assessed the role of ESO on the PI3K/AKT/FOXO3a pathway and the beneficial effects of ESO combined with 3-MA in gastric cancer cells. Cell viability, proliferation, invasion, migration, apoptosis, autophagy, and protein expression were detected by CCK-8, EdU, Transwell, flow cytometry, immunofluorescence assay, and western blot. ESO decreased cell viability in a concentration- and time-dependent manner and increased autophagy with upregulation of LC3II and P62. Additionally, ESO inhibited the proliferation, migration, and invasion and induced the apoptosis of gastric cancer cells in a concentration-dependent manner. ESO inhibited PI3K/AKT/FOXO3a signaling and EGFR and SKP2 expression concentration-dependent. 3-MA enhanced the antiproliferative activity of ESO and synergistically inhibited PI3K/FOXO3a signaling and the expression of EGFR but not SKP2. Furthermore, pretreatment with the EGFR inhibitor AG1478 enhanced the antiproliferative activity of ESO in gastric cancer cells. In conclusion, our results suggested that the PI3K inhibitor 3-MA promotes the antiproliferative activity of ESO in gastric cancer cells by synergistically downregulating EGFR via the PI3K/FOXO3a pathway.
    Keywords:  EGFR; Esomeprazole; Gastric cancer cells; PI3K inhibitor; Proliferation
    DOI:  https://doi.org/10.1016/j.biopha.2022.112665
This page is being maintained by Thomas Krichel. It was last updated on 2022‒03‒06 at 14:50:25.