Mitochondriotropic antioxidant based on caffeic acid AntiOxCIN4 activates Nrf2-dependent antioxidant defenses and quality control mechanisms to antagonize oxidative stress-induced cell damage

Mitochondria in the cell are the center for energy production, essential biomolecule synthesis, and cell fate determination. Moreover, the mitochondrial functional versatility enables cells to adapt to the changes in cellular environment and various stresses. In the process of discharging its cellular duties, mitochondria face multiple types of challenges, such as oxidative stress, protein-related challenges (import, folding, and degradation) and mitochondrial DNA damage. They mitigate all these challenges with robust quality control mechanisms which include antioxidant defenses, proteostasis systems (chaperones and proteases) and mitochondrial biogenesis. Failure of these quality control mechanisms leaves mitochondria as terminally damaged, which then have to be promptly cleared from the cells before they become a threat to cell survival. Such damaged mitochondria are degraded by a selective form of autophagy called mitophagy. Rigorous research in the field has identified multiple types of mitophagy processes based on targeting signals on damaged or superfluous mitochondria. In this review, we provide an in-depth overview of mammalian mitophagy and its importance in human health and diseases. We also attempted to highlight the future area of investigation in the field of mitophagy.

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Spirulina Platensis Supplementation Coupled to Strength Exercise Improves Redox Balance and Reduces Intestinal Contractile Reactivity in Rat Ileum

Marine Drugs ◽

10.3390/md18020089 ◽

2020 ◽

Vol 18 (2) ◽

pp. 89

Author(s):

Layanne C. C. Araujo ◽

Aline F. Brito ◽

Iara L. L. Souza ◽

Paula B. Ferreira ◽

Luiz Henrique C. Vasconcelos ◽

...

Keyword(s):

Oxidative Stress ◽

Strength Training ◽

Spirulina Platensis ◽

Cell Damage ◽

Redox Balance ◽

Antioxidant Defenses ◽

Rat Ileum ◽

Beneficial Effects ◽

Dpph Method ◽

Male Wistar Rats

The blue alga Spirulina platensis has presented several pharmacological activities, highlighting its actions as an anti-inflammatory and antioxidant. In addition, there are few studies with the influence of strength training on physiological parameters, as intestinal contractility and oxidative cell damage. We evaluated the influence of S. platensis supplementation, strength training, and its association on contractile reactivity of rat ileum, as well as the balance of oxidative stress/antioxidant defenses. Methods: Male Wistar rats were divided into; sedentary (S); S + supplemented with algae at 50 (S50), 150 (S150), and 500 mg/kg (S500); trained (T); and T + supplemented (T50, T150, and T500). Contractile reactivity was analyzed by kymographs; oxidative stress on ileum by the malondialdehyde (MDA) formation; and the antioxidant capacity by 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. S. platensis supplementation reduced the reactivity of rat ileum to carbachol (CCh) and KCl, while training reduced only the CCh efficacy. In addition, association potentiated the reduction on contractile reactivity. Supplementation reduced the oxidative stress and increased oxidation inhibition; training alone did not alter this parameter, however association potentiated this beneficial effect. Therefore, this study demonstrated that both supplementation and its association with strength training promote beneficial effects regarding intestinal contractile reactivity and oxidative stress, providing new insights for intestinal disorders management.

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Administration of Enalapril Started Late in Life Attenuates Hypertrophy and Oxidative Stress Burden, Increases Mitochondrial Mass and Modulates Mitochondrial Quality Control Signaling in the Rat Heart

10.20944/preprints201809.0234.v1 ◽

2018 ◽

Author(s):

Anna Picca ◽

Giuseppe Sirago ◽

Vito Pesce ◽

Angela Maria Serena Lezza ◽

Riccardo Calvani ◽

...

Keyword(s):

Oxidative Stress ◽

Quality Control ◽

Oxidative Damage ◽

Cardiac Hypertrophy ◽

Citrate Synthase ◽

Late Life ◽

Antioxidant Defenses ◽

Mitochondrial Quality Control ◽

Mitochondrial Mass ◽

And Oxidative Stress

Mitochondrial dysfunction is relevant mechanism in cardiac aging. Here, we investigated the effects of late-life enalapril administration at non-antihypertensive dose on mitochondrial genomic stability, oxidative damage, and mitochondrial quality control (MQC) signaling in the heart of aged rats. The protein expression of selected mediators (i.e., mitochondrial antioxidant enzymes, energy metabolism, mitochondrial biogenesis, dynamics, and autophagy) was measured in old rats randomly assigned to receive enalapril (n=8) or placebo (n=8) from 24 to 27 months of age. We also assessed mitochondrial DNA (mtDNA) content, citrate synthase activity, oxidative lesions to protein and mtDNA (i.e., carbonyls and abundance of mtDNA4834 deletion), and mitochondrial transcription factor A (TFAM) binding to specific mtDNA regions. Enalapril attenuated cardiac hypertrophy and oxidative stress-derived damage (mtDNA oxidation, mtDNA4834 deletion, and protein carbonylation), while increasing mitochondrial antioxidant defenses. TFAM binding to mtDNA regions involved in replication and deletion generation was increased following enalapril administration. Increased mitochondrial mass as well as mitochondriogenesis and autophagy signaling was found in enalapril-treated rats. Late-life enalapril administration mitigates age-dependent cardiac hypertrophy and oxidative damage, while increasing mitochondrial mass and modulating MQC signaling. Further analyses are needed to conclusively establish whether enalapril may offer cardioprotection during aging.

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Role of sperm apoptosis and oxidative stress in male infertility: A narrative review

International Journal of Reproductive BioMedicine ◽

10.18502/ijrm.v19i6.9371 ◽

2021 ◽

Author(s):

Asadollah Asadi ◽

Rozita Ghahremani ◽

Arash Abdolmaleki ◽

Farzad Rajaei

Keyword(s):

Oxidative Stress ◽

Quality Control ◽

Male Infertility ◽

Dna Fragmentation ◽

Germ Cells ◽

Male Reproduction ◽

Future Research ◽

Dna Integrity ◽

Control Mechanisms

Activation of caspase, externalization of phosphatidyl serine, change in the mitochondrial membrane potential, and DNA fragmentation are apoptosis markers found in human ejaculated spermatozoa. Also, reactive oxygen species (ROS) play a vital role in the different types of male infertility. In this review, data sources including Google Scholar, Scopus, PubMed, and Science Direct were searched for publications with no particular time restriction to get a holistic and comprehensive view of the research. Apoptosis regulates the male germ cells, correct function and development from the early embryonic stages of gonadal differentiation to fertilization. In addition to maintaining a reasonable ratio between the Sertoli and germ cells, apoptosis is one of the well-known quality control mechanisms in the testis. Also, high ROS levels cause a heightened and dysregulated apoptotic response. Apoptosis is one of the well-known mechanisms of quality control in the testis. Nevertheless, increased apoptosis may have adverse effects on sperm production. Recent studies have shown that ROS and the consequent oxidative stress play a crucial role in apoptosis. This review aims to assimilate and summarize recent findings on the apoptosis in male reproduction and fertility. Also, this review discusses the update on the role of ROS in normal sperm function to guide future research in this area. Key words: Fertility, Spermatogonia, Apoptosis, Reproduction, DNA fragmentation, DNA integrity, ROS.

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Neuroprotective Effects of Extracts from the Radix Curcuma aromatica on H2O2-induced Damage in PC12 Cells

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207321666181005121457 ◽

2018 ◽

Vol 21 (8) ◽

pp. 571-582 ◽

Cited By ~ 1

Author(s):

Juxiang Liu ◽

Lianli Zhang ◽

Dan Liu ◽

Baocai Li ◽

Mi Zhang

Keyword(s):

Oxidative Stress ◽

Pc12 Cells ◽

Caspase 3 ◽

Cell Damage ◽

Positive Control ◽

Neuroprotective Activity ◽

Antioxidant Enzyme Activities ◽

Morphologic Change ◽

Neuroprotective Effects ◽

Etoh Extract

Aim & Objectives: Curcuminoids are characteristic constituents in Curcuma, displaying obviously neuroprotective activities against oxidative stress. As one of the Traditional Chinese Medicines from Curcuma, the radix of Curcuma aromatica is also rich in those chemicals, but its neuroprotective activity and mechanism remain unknown. The aim of the current study is to evaluate the neuroprotective effects of extracts from the radix of C. aromatica (ECAs) on H2O2-damaged PC12 cells. Material and Methods: The model of oxidative stress damage was established by treatment of 400 µM H2O2 on PC12 to induce cell damage. After the treatment of ECWs for 24 h, the cell viability, LDH, SOD, CAT and GSH were measured to evaluate the neuroprotection of ECAs on that model. The potential action mechanism was studied by measurement of level of ROS, cell apoptosis rate, mitochondrial membrane potential (MMP), morphologic change, the intracellular Ca2+ content (F340/F380) and the expressions of Bcl-2, Bax and Caspase-3. Additionally, the constituents from tested extracts were analyzed by HPLC-DAD-Q-TOF-MS method. Results: Compared with a positive control, Vitamin E, 10 µg/ml of 95% EtOH extract (HCECA) and 75% EtOH extract (MCECA) can markedly increase the rate of cell survival and enhance the antioxidant enzyme activities of SOD, CAT, increase the levels of GSH, decrease LDH release and the level of ROS, attenuate the intracellular Ca2+ overloading, reduce the cell apoptotic rate and stabilize MMP, down-regulate Bcl-2 expression, up-regulate Bax and caspase-3 expression, and improve the change of cell morphology. The chemical analysis showed that diarylheptanoids and sesquiterpenoids are the major chemicals in tested extracts and the former were richer in HCECA and MCECA than others. Conclusions: These findings indicated that the effects of HCECA and MCECA on inhibiting the cells damage induced by H2O2 in PC12 are better than other extracts from the radix of C. aromatica, and the active constituents with neuroprotective effects consisting in those two active extracts are diarylheptanoids.

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MicroRNAs in Noise-Induced Hearing Loss and their Regulation by Oxidative Stress and Inflammation

Current Drug Targets ◽

10.2174/1389450121666200615145552 ◽

2020 ◽

Vol 21 (12) ◽

pp. 1216-1224

Author(s):

Fatemeh Forouzanfar ◽

Samira Asgharzade

Keyword(s):

Oxidative Stress ◽

Hearing Loss ◽

Hair Cell ◽

Noise Exposure ◽

Cell Damage ◽

Sensory Cells ◽

Noise Induced Hearing Loss ◽

Irreversible Damage ◽

Open Access Journals

Noise exposure (NE) has been recognized as one of the causes of sensorineural hearing loss (SNHL), which can bring about irreversible damage to sensory hair cells in the cochlea, through the launch of oxidative stress pathways and inflammation. Accordingly, determining the molecular mechanism involved in regulating hair cell apoptosis via NE is essential to prevent hair cell damage. However, the role of microRNAs (miRNAs) in the degeneration of sensory cells of the cochlea during NE has not been so far uncovered. Thus, the main purpose of this study was to demonstrate the regulatory role of miRNAs in the oxidative stress pathway and inflammation induced by NE. In this respect, articles related to noise-induced hearing loss (NIHL), oxidative stress, inflammation, and miRNA from various databases of Directory of Open Access Journals (DOAJ), Google Scholar, PubMed; Library, Information Science & Technology Abstracts (LISTA), and Web of Science were searched and retrieved. The findings revealed that several studies had suggested that up-regulation of miR-1229-5p, miR-451a, 185-5p, 186 and down-regulation of miRNA-96/182/183 and miR-30b were involved in oxidative stress and inflammation which could be used as biomarkers for NIHL. There was also a close relationship between NIHL and miRNAs, but further research is required to prove a causal association between miRNA alterations and NE, and also to determine miRNAs as biomarkers indicating responses to NE.

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Cytosolic protein quality control machinery: Interactions of Hsp70 with a network of co-chaperones and substrates

Experimental Biology and Medicine ◽

10.1177/1535370221999812 ◽

2021 ◽

pp. 153537022199981

Author(s):

Chamithi Karunanayake ◽

Richard C Page

Keyword(s):

Quality Control ◽

Protein Quality ◽

Protein Quality Control ◽

Structural Features ◽

Cellular Protein ◽

Mechanisms Of Action ◽

Control Mechanisms ◽

Nucleotide Exchange ◽

Domain Organization ◽

Nucleotide Exchange Factors

The chaperone heat shock protein 70 (Hsp70) and its network of co-chaperones serve as a central hub of cellular protein quality control mechanisms. Domain organization in Hsp70 dictates ATPase activity, ATP dependent allosteric regulation, client/substrate binding and release, and interactions with co-chaperones. The protein quality control activities of Hsp70 are classified as foldase, holdase, and disaggregase activities. Co-chaperones directly assisting protein refolding included J domain proteins and nucleotide exchange factors. However, co-chaperones can also be grouped and explored based on which domain of Hsp70 they interact. Here we discuss how the network of cytosolic co-chaperones for Hsp70 contributes to the functions of Hsp70 while closely looking at their structural features. Comparison of domain organization and the structures of co-chaperones enables greater understanding of the interactions, mechanisms of action, and roles played in protein quality control.

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COVID-19 Brings Data Equity Challenges to the Fore

Digital Government: Research and Practice (DGOV) ◽

10.1145/3440889 ◽

2021 ◽

Author(s):

H.V. Jagadish ◽

Julia Stoyanovich ◽

Bill Howe

Keyword(s):

Quality Control ◽

Government Policy ◽

Data Driven ◽

Contact Tracing ◽

Control Mechanisms ◽

Sources Of Information ◽

Decision Systems ◽

Physical Resources ◽

Multiple Levels ◽

Data Driven Decisions

The COVID-19 pandemic is compelling us to make crucial data-driven decisions quickly, bringing together diverse and unreliable sources of information without the usual quality control mechanisms we may employ. These decisions are consequential at multiple levels: they can inform local, state and national government policy, be used to schedule access to physical resources such as elevators and workspaces within an organization, and inform contact tracing and quarantine actions for individuals. In all these cases, significant inequities are likely to arise, and to be propagated and reinforced by data-driven decision systems. In this article, we propose a framework, called FIDES, for surfacing and reasoning about data equity in these systems.

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Oxidative Stress and Inflammation in Renal and Cardiovascular Complications of Diabetes

Biology ◽

10.3390/biology10010018 ◽

2020 ◽

Vol 10 (1) ◽

pp. 18

Author(s):

Amelia Charlton ◽

Jessica Garzarella ◽

Karin A. M. Jandeleit-Dahm ◽

Jay C. Jha

Keyword(s):

Oxidative Stress ◽

Cardiovascular Disease ◽

Tissue Injury ◽

Cardiovascular Complications ◽

Therapeutic Strategies ◽

Cellular Damage ◽

Antioxidant Defenses ◽

Pathological State ◽

Oxygen Species ◽

Emerging Therapies

Oxidative stress and inflammation are considered major drivers in the pathogenesis of diabetic complications, including renal and cardiovascular disease. A symbiotic relationship also appears to exist between oxidative stress and inflammation. Several emerging therapies target these crucial pathways, to alleviate the burden of the aforementioned diseases. Oxidative stress refers to an imbalance between reactive oxygen species (ROS) and antioxidant defenses, a pathological state which not only leads to direct cellular damage but also an inflammatory cascade that further perpetuates tissue injury. Emerging therapeutic strategies tackle these pathways in a variety of ways, from increasing antioxidant defenses (antioxidants and Nrf2 activators) to reducing ROS production (NADPH oxidase inhibitors and XO inhibitors) or inhibiting the associated inflammatory pathways (NLRP3 inflammasome inhibitors, lipoxins, GLP-1 receptor agonists, and AT-1 receptor antagonists). This review summarizes the mechanisms by which oxidative stress and inflammation contribute to and perpetuate diabetes associated renal and cardiovascular disease along with the therapeutic strategies which target these pathways to provide reno and cardiovascular protection in the setting of diabetes.

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Anti-diabetes Constituents in Leaves of Smallanthus sonchifolius

Natural Product Communications ◽

10.1177/1934578x1000500123 ◽

2010 ◽

Vol 5 (1) ◽

pp. 1934578X1000500 ◽

Cited By ~ 3

Author(s):

Xiang Zheng ◽

He Fan ◽

Kang Ting-Guo ◽

Dou De-Qiang ◽

Gai Kuo ◽

...

Keyword(s):

Quality Control ◽

Chlorogenic Acid ◽

Caffeic Acid ◽

Analytical Method ◽

Inhibitory Effect ◽

Hplc Method ◽

Smallanthus Sonchifolius ◽

Rp Hplc

The inhibitory effect of smallanthaditerpenic acids A, B, C and D previously isolated from leaves of Smallanthus sonchifolius (yacon) on α-glucosidase were examined and their IC50 were determined to be 0.48 mg/mL, 0.59 mg/mL, 1.00 mg/mL, and 1.17 mg/mL respectively. In addition, a rapid, reliable RP-HPLC method for the analysis of chlorogenic acid, caffeic acid, and smallanthaditerpenic acids A and C in yacon leaves was established, and the variation in their contents in leaves from plants cultivated in different places and collected at different times of the year were compared. The established analytical method for determining smallanthaditerpenic acids A and C, chlorogenic acid and caffeic acid presented good results and could be used as a method for the quality control of S. sonchifolius leaves.

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