scholarly journals Autophagy facilitates age-related cell apoptosis—a new insight from senile cataract

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Jiani Huang ◽  
Wangshu Yu ◽  
Qin He ◽  
Xiaoying He ◽  
Ming Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Prolonged Exposure ◽  
Cell Loss ◽  
Senile Cataract ◽  
Associated Diseases ◽  
Related Cell ◽  
Age Related ◽  
Healthy Donors ◽  
Induced Apoptosis ◽  
Autophagy Activity

AbstractAge-related cell loss underpins many senescence-associated diseases. Apoptosis of lens epithelial cells (LECs) is the important cellular basis of senile cataract resulted from prolonged exposure to oxidative stress, although the specific mechanisms remain elusive. Our data indicated the concomitance of high autophagy activity, low SQSTM1/p62 protein level and apoptosis in the same LEC from senile cataract patients. Meanwhile, in primary cultured LECs model, more durable autophagy activation and more obvious p62 degradation under oxidative stress were observed in LECs from elder healthy donors, compared with that from young healthy donors. Using autophagy-deficiency HLE-B3 cell line, autophagy adaptor p62 was identified as the critical scaffold protein sustaining the pro-survival signaling PKCι-IKK-NF-κB cascades, which antagonized the pro-apoptotic signaling. Moreover, the pharmacological inhibitor of autophagy, 3-MA, significantly inhibited p62 degradation and rescued oxidative stress-induced apoptosis in elder LECs. Collectively, this study demonstrated that durable activation of autophagy promoted age-related cell death in LECs. Our work contributes to better understanding the pathogenesis of senescence-associated diseases.

scholarly journals Age-related increase of oxidative stress-induced apoptosis in micePrevention by Ginkgo biloba extract (EGb761)

2001 ◽  
Vol 108 (8) ◽  
pp. 969-978 ◽  
Author(s):  
K. Schindowski ◽  
S. Leutner ◽  
S. Kressmann ◽  
A. Eckert ◽  
W. E. Müller
Keyword(s):  
Oxidative Stress ◽  
Ginkgo Biloba ◽  
Ginkgo Biloba Extract ◽  
Age Related ◽  
Induced Apoptosis ◽  
Related Increase

scholarly journals OXIDATIVE STRESS IN AGING

2020 ◽  
pp. 10-22
Author(s):  
Н. К. Зенков ◽  
П. М. Кожин ◽  
А. В. Чечушков ◽  
Н. В. Кандалинцева ◽  
Г. Г. Мартинович ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Defense Mechanisms ◽  
Redox Balance ◽  
Ros Generation ◽  
Free Radical Theory ◽  
Radical Theory ◽  
Age Related ◽  
Theory Of Aging ◽  
Autophagy Activity ◽  
Important System

Выдвинутая более 50 лет назад Д. Харманом свободнорадикальная теория старения остается популярной и сегодня. В обзоре проведен анализ возрастных изменений основных эндогенных механизмов продукции активированных кислородных метаболитов (АКМ) и механизмов антиоксидантной защиты. С возрастом генерация АКМ митохондриями, пероксисомами и NAD(P) H -оксидазами усиливается, в то время как транскрипционная активность важной системы поддержания редокс-баланса Keap 1/ Nrf 2/ ARE уменьшается. У старых животных отмечается также низкая активность аутофагии, удаляющей из клеток поврежденные органеллы и агрегированные структуры. Возрастное смещение редокс-баланса в сторону окислительного стресса может являться причиной развития возраст-ассоциированных нейрогеденеративных, аутоиммунных и воспалительных патологий. The free-radical theory of aging, advanced more than 50 years ago by D. Harman, remains popular today. The review analyzes age-related changes in the main endogenous mechanisms of reactive oxygen species (ROS) production and antioxidant defense mechanisms. With age, ROS generation by mitochondria, peroxisomes, and NAD(P)H oxidases is enhanced, while the transcriptional activity of the important system Keap 1/ Nrf 2/ ARE maintaining redox balance decreases. In old animals, autophagy activity is also low, which removes damaged organelles and aggregated structures from cells. The age-related shift of the redox balance towards oxidative stress can cause the development of age-associated neurodegenerative, autoimmune and infl ammatory pathologies.

scholarly journals AβPP-induced UPR Transcriptomic Signature of Glial Cells to Oxidative Stress as an Adaptive Mechanism to Preserve Cell Function and Survival

2018 ◽  
Vol 15 (7) ◽  
pp. 643-654 ◽  
Author(s):  
Naima Chalour ◽  
Agathe Maoui ◽  
Patrice Rat ◽  
France Massicot ◽  
Melody Dutot ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Er Stress ◽  
Cell Function ◽  
Amyloid Β ◽  
Redox Status ◽  
Age Related Macular Degeneration ◽  
Amyloid Β Protein ◽  
Major Genes ◽  
Age Related ◽  
Induced Apoptosis

Background: Alzheimer's disease (AD) and age-related macular degeneration (AMD) present similarities, particularly with respect to oxidative stress, including production of 4-Hydroxy-2- nonenal (HNE). AMD has been named the AD in the eye. The Müller cells (MC) function as a principal glia of the retina and maintain water/potassium, glutamate homeostasis and redox status. Any MC dysfunction results in retinal neurodegeneration. Objectives: We investigated the effects of HNE in human MC. Results: HNE induced an increase of the reactive oxygen species associated with mitochondrial dysfunction and apoptosis. HNE induced endoplasmic reticulum (ER) stress (upregulation of GRP78/Bip, and the proapoptotic factor, CHOP). HNE also impaired expression of genes controlling potassium homeostasis (KCNJ10), glutamate detoxification (GS), and the visual cycle (RLBP1). MC adaptive response to HNE included upregulation of amyloid-β protein precursor (AβPP). To determine the role of AβPP, we overexpressed AβPP in MC. Overexpression of AβPP induced strong antioxidant and anti-ER stress (PERK downregulation and GADD34 upregulation) responses accompanied by activation of the prosurvival branch of the unfolded protein response. It was also associated with upregulation of major genes involved in MC-controlled retinal homeostasis (KCNJ10, GS, and RLBP1) and protection against HNE-induced apoptosis. Therefore, AβPP is an ER and oxidative stress responsive molecule, and is able to stimulate the transcription of major genes involved in MC functions impaired by HNE. Conclusion: Our study suggests that targeting oxidative and ER stress might be a potential therapeutic strategy against glia impairment in AMD and AD, in light of the common features between the two pathologies.

Long term treadmill exercise affects age-related oxidative stress in the spinal cord of rats

2020 ◽  
pp. 1-8
Author(s):  
G. Shokouhi ◽  
N. Ahmadiasl ◽  
L. Roshangar ◽  
A. Ghorbanihaghjo ◽  
F. Sheikhzadeh ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Treadmill Exercise ◽  
Male Rats ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Control Groups ◽  
Antioxidant Defence ◽  
Age Related ◽  
Induced Apoptosis

Age-induced apoptosis is believed to be caused by the imbalance between production of reactive oxygen species (ROS) and human body antioxidant defence. Regular aerobic treadmill-exercise has been suggested to enhance the antioxidant defence. This study aimed to investigate the effects of long-term treadmill exercise on age-related oxidative stress and the apoptosis of oligodendrocytes in the spinal cord of the rat. Sixty male rats were divided into six groups: three exercised groups, which underwent 6, 9 and 12 months of mild-to-moderate treadmill exercise and three non-exercised control groups. Spinal cord white or grey matter tissue sampling was done through mid-thoracic laminectomy. The malondialdehyde (MDA; indicator of oxidative stress) levels, the number of apoptotic oligodendrocytes and ultrastructural alterations were also evaluated. Our data showed that treadmill exercise resulted in decreased lipid peroxidation and the number of apoptotic oligodendrocytes in the spinal cord of rats, as compared to non-exercised animals. These results were confirmed by TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labelling) staining and electron microscope. This study suggests that the long-term treadmill exercise can affect oxidative stress and oligodendrocytes apoptosis in the spinal cord of aged rats and further studies are needed to validate these findings in humans.

N-acetyl-l-cysteine protects intestinal lymphocytes from apoptotic death after acute exercise in adrenalectomized mice

2005 ◽  
Vol 288 (6) ◽  
pp. R1664-R1672 ◽  
Author(s):  
Joe Quadrilatero ◽  
Laurie Hoffman-Goetz
Keyword(s):  
Oxidative Stress ◽  
Acute Exercise ◽  
Apoptotic Cell ◽  
Cell Loss ◽  
Strenuous Exercise ◽  
Lymphocyte Apoptosis ◽  
Mitochondrial Membrane Depolarization ◽  
Exercise Induced ◽  
Induced Apoptosis ◽  
Intestinal Lymphocyte

Lymphocyte apoptosis has been observed after strenuous exercise. Both glucocorticoids (GC) and reactive oxygen species (ROS) have been suggested to contribute to exercise-induced lymphocyte apoptosis. The aims of this study were to 1) examine the direct contribution of GC during exercise-induced intestinal lymphocyte (IL) apoptosis and 2) determine the contribution of oxidative stress, in the absence of GC, to exercise-induced IL apoptosis. Mice were bilaterally adrenalectomized (ADX) and randomly assigned to receive saline (SAL) or N-acetyl-l-cysteine (NAC) 30 min before treadmill exercise (EX). EX consisted of 90 min of continuous running at a 2° slope (30 min at 22 m/min, 30 min at 25 m/min; and 30 min at 28 m/min), and then killed immediately (Imm) or 24 h (24h) postexercise. Control mice were exposed to a nonexercised (NonEX) condition consisting of treadmill noise and vibration without running. ILs were isolated and measured for apoptotic (phosphatidylserine externalization, mitochondrial membrane depolarization, Bcl-2, caspase 3, and cytosolic cytochrome c) and oxidative stress (H2O2and glutathione) markers. Plasma was analyzed for corticosterone (CORT) by radioimmunoassay. ADX eliminated the exercise-induced elevation in CORT but did not prevent IL apoptosis and cell loss relative to NonEX mice. In contrast, administration of NAC to ADX mice protected ILs from apoptotic cell death and inhibited post-exercise cell loss. These findings suggest that GC are not responsible for exercise-induced apoptosis and cell loss of ILs. The protective effect provided by the antioxidant NAC strongly suggest that oxidative stress is the primary pathway for IL apoptosis and cell loss after strenuous exercise.

scholarly journals Potential Protective Activities of Extracts of Phellinus linteus and the Altered Expressions of GSTM3 on Age-Related Cataract

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Cheng-Hsiu Lin ◽  
Chun-Ching Shih
Keyword(s):  
Oxidative Stress ◽  
The Elderly ◽  
Senile Cataract ◽  
Protective Effects ◽  
Phellinus Linteus ◽  
Glutathione S Transferase ◽  
Treatment Groups ◽  
Age Related ◽  
Preventive Activity ◽  
Protein Expressions

Age-related cataract (ARC) is one of the leading causes of visual impairment and blindness worldwide among the elderly. Here, we used sodium selenite-induced cataract mouse model, which shares with similarities with human senile cataract to investigate whether the extracts of Phellinus linteus (PLE) could have the potential protective effects of ARC or not. The mice pups were randomly divided into 4 treatment groups (n = 7): (1) normal saline on postpartum day 26; (2) Na selenite injected s.c on day 26; (3) Na selenite s.c on day 26+ gavaged PLE (40 mg/kg) on days 26–47; and (4) Na selenite s.c on day 26 + resveratrol on days 26–47. On day 47, encapsulated lenses and plasma were analyzed for the levels of glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA), a marker of lipid peroxidation. Lens epithelial cells (LECs) were also analyzed for the mRNA and protein expressions of glutathione S-transferase Mu (GSTM3). We demonstrated that PLE could prevent selenite-induced oxidative stress and cataract formation in mice by higher GSH and SOD and lower MDA in LECs, plasma, and liver tissues and the increases in the mRNA and protein expressions of GSTM3 in LECs. Our data show the increasing oxidative stress in selenite-induced cataract mice. Our data reveal the benefits of PLE for preventive activity in selenite-induced cataract in mice and there is a good possibility that PLE could ameliorate human senile cataract.

scholarly journals Cytoprotective Effects of Delphinidin for Human Chondrocytes against Oxidative Stress through Activation of Autophagy

Antioxidants ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 83 ◽  
Author(s):  
Dong-Yeong Lee ◽  
Young-Jin Park ◽  
Myung-Geun Song ◽  
Deok Ryong Kim ◽  
Sahib Zada ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Caspase 3 ◽  
Critical Role ◽  
Antioxidant Response ◽  
Human Chondrocytes ◽  
Nuclear Factor ◽  
Acridine Orange Staining ◽  
Oxidative Stresses ◽  
Age Related ◽  
Induced Apoptosis

Antioxidant enzymes are decreased in osteoarthritis (OA) patients, implying the role of oxidative stress in osteoarthritis pathogenesis. The aim of this study was to evaluate the cytoprotective effects of delphinidin, a potent antioxidant, in human chondrocytes and the underlying mechanisms. The cytoprotective mechanism induced by delphinidin against oxidative stress (H2O2) in human chondrocytes was investigated. Cell viability and death were evaluated using proapoptotic and antiapoptotic markers such as cleaved caspase-3 (c-caspase-3), cleaved poly(ADP-ribose) polymerase N-acetylcysteine (c-PARP), Bcl-XL, and transcription factors associated with redox and inflammation regulation, including nuclear factor kappa B (NF-κB) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Induction of autophagy was assessed by formation of LC3-II and autophagosome-(LC3 punctate, monodansylcadaverine (MDC) and acridine orange staining) in the presence or absence of an autophagy inhibitor. Treatment with delphinidin itself at concentration below 50 µM for 24 h did not affect viability of chondrocytes. Delphinidin inhibited reactive oxygen species (ROS)-induced apoptosis by significantly decreasing apoptosis markers such as c-caspase-3 and c-PARP while increasing antiapoptotic marker Bcl-XL and antioxidant response NF-κB and Nrf2 pathways. Delphinidin also activated cytoprotective autophagy to protect chondrocytes during oxidative stresses. Activation of autophagy with autophagy inducer rapamycin also inhibited ROS-induced cell death and decreased proapoptotic proteins but increased antiapoptotic protein Bcl-XL, NF-κB, and Nrf2. Delphinidin can protect chondrocytes against H2O2-induced apoptosis via activation of Nrf2 and NF-κB and protective autophagy. Thus, it can inhibit OA with protection of chondrocytes. Delphinidin can protect chondrocytes against H2O2-induced ROS with maintenance of homeostasis and redox. These results suggest that delphinidin could be used to protect chondrocytes against age-related oxidative stress and other oxidative stresses in the treatment of OA. Thus, delphinidin may play a critical role in preventing the development and progression of OA.

scholarly journals The interplay of autophagy and oxidative stress in the pathogenesis and therapy of retinal degenerative diseases

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Kun-Che Chang ◽  
Pei-Feng Liu ◽  
Chia-Hsuan Chang ◽  
Ying-Cheng Lin ◽  
Yen-Ju Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Age Related Macular Degeneration ◽  
Ocular Diseases ◽  
Age Related ◽  
Transcription Factor Activation ◽  
Physiological Homeostasis ◽  
Retinal Degenerative Diseases ◽  
Cellular Components ◽  
Autophagy Activity ◽  
And Oxidative Stress

AbstractOxidative stress is mainly caused by intracellular reactive oxygen species (ROS) production, which is highly associated with normal physiological homeostasis and the pathogenesis of diseases, particularly ocular diseases. Autophagy is a self-clearance pathway that removes oxidized cellular components and regulates cellular ROS levels. ROS can modulate autophagy activity through transcriptional and posttranslational mechanisms. Autophagy further triggers transcription factor activation and degrades impaired organelles and proteins to eliminate excessive ROS in cells. Thus, autophagy may play an antioxidant role in protecting ocular cells from oxidative stress. Nevertheless, excessive autophagy may cause autophagic cell death. In this review, we summarize the mechanisms of interaction between ROS and autophagy and their roles in the pathogenesis of several ocular diseases, including glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and optic nerve atrophy, which are major causes of blindness. The autophagy modulators used to treat ocular diseases are further discussed. The findings of the studies reviewed here might shed light on the development and use of autophagy modulators for the future treatment of ocular diseases.

scholarly journals PTEN Reduced UVB-Mediated Apoptosis in Retinal Pigment Epithelium Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Jia He ◽  
Chongde Long ◽  
Zixin Huang ◽  
Xin Zhou ◽  
Xielan Kuang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Molecular Mechanisms ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Rpe Cells ◽  
Age Related ◽  
Induced Apoptosis

Age-related macular degeneration (AMD) is a leading cause of blindness and progressive loss of central vision in the elderly population. The important factor of AMD pathogenesis is the degeneration of retinal pigment epithelial (RPE) cells by oxidative stress. Inactivation of PTEN can disrupt intercellular adhesion in the RPE cells, but the mechanism of oxidative stress is less known. Here we presented evidence that UVB-mediated oxidative stress induced apoptosis in ARPE-19 cells. Downregulation of the expression of PTEN in UVB-irradiative RPE cells triggered DNA damage and increased the level of UVB-induced apoptosis by activating p53-dependent pathway. However, overexpression of PTEN increased cell survival by suppressing p-H2A in response to DNA damage and apoptosis. When using Pifithrin-α(one of p53 inhibitors), the level of p53-dependent apoptosis was significantly lower than untreated, which suggested that p53 was possibly involved in PTEN-dependent apoptosis. Thus, it elucidated the molecular mechanisms of UVB-induced damage in RPE cells and may offer an alternative therapeutic target in dry AMD.

No age-related cell loss in three retinal nuclear layers of the Long-Evans rat

2007 ◽  
Vol 24 (6) ◽  
pp. 799-803 ◽  
Author(s):  
LIXIA FENG ◽  
ZHAOXIA SUN ◽  
HUI HAN ◽  
YIFENG ZHOU ◽  
MING ZHANG
Keyword(s):  
Ganglion Cell Layer ◽  
Ganglion Cells ◽  
Cell Layer ◽  
Outer Nuclear Layer ◽  
Photoreceptor Cells ◽  
Cell Loss ◽  
Related Cell ◽  
Age Related ◽  
Long Evans ◽  
Number Of Cells

The retina mainly contains ganglion, bipolar and photoreceptor cells which are distributed in the ganglion cell layer (GCL), inner nuclear layer (INL) and outer nuclear layer (ONL), respectively. Whether there is an age-related loss of these retinal cells remains not well understood. Cell density and the total number of cells were two commonly used measures to evaluate such age-related changes in most previous studies and provided controversial conclusions. The use of density measures as decisive data is problematic because the total area of the retina was expanded in aging, whereas the application of the total number of cells was limited for assessing ganglion cells. In this study, thus, we wanted to test whether there is an age-related cell loss in the GCL, INL and ONL and if so, whether such a loss is correlated to the convergence ratio of these cells. We used stereological procedures to quantify the total number of cells in the three retinal nuclear layers in six young and six aged Long-Evans rats. We found that during aging, the total volume of the retina remained unchanged, but the retina became thinner. There was no cell loss in each individual nuclear layer, and the ratio of the ONL to INL to GCL was preserved.

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