Curcumin, a Multifaceted Hormetic Agent, Mediates an Intricate Crosstalk between Mitochondrial Turnover, Autophagy, and Apoptosis

Rainey, Nathan Earl; Moustapha, Aoula; Petit, Patrice X.

doi:10.1155/2020/3656419

Cited by 53 publications

(29 citation statements)

References 233 publications

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“…The common denominator for its potential protective role in neurodegenerative disorders is the enhancement of the cell stress response, mainly due to the heme oxygenase-1 system [ 57 ]. Curcumin mediates an intricate crosstalk between mitochondrial turnover, autophagy, and apoptosis [ 58 ]. Curcumin was recently reported to regulate ROS hormesis by favoring mitochondrial fusion/elongation, biogenesis, and improved function in rodent muscle cells [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Less Can Be More: The Hormesis Theory of Stress Adaptation in the Global Biosphere and Its Implications

Schirrmacher¹

2021

Biomedicines

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A dose-response relationship to stressors, according to the hormesis theory, is characterized by low-dose stimulation and high-dose inhibition. It is non-linear with a low-dose optimum. Stress responses by cells lead to adapted vitality and fitness. Physical stress can be exerted through heat, radiation, or physical exercise. Chemical stressors include reactive species from oxygen (ROS), nitrogen (RNS), and carbon (RCS), carcinogens, elements, such as lithium (Li) and silicon (Si), and metals, such as silver (Ag), cadmium (Cd), and lead (Pb). Anthropogenic chemicals are agrochemicals (phytotoxins, herbicides), industrial chemicals, and pharmaceuticals. Biochemical stress can be exerted through toxins, medical drugs (e.g., cytostatics, psychopharmaceuticals, non-steroidal inhibitors of inflammation), and through fasting (dietary restriction). Key-lock interactions between enzymes and substrates, antigens and antibodies, antigen-presenting cells, and cognate T cells are the basics of biology, biochemistry, and immunology. Their rules do not obey linear dose-response relationships. The review provides examples of biologic stressors: oncolytic viruses (e.g., immuno-virotherapy of cancer) and hormones (e.g., melatonin, stress hormones). Molecular mechanisms of cellular stress adaptation involve the protein quality control system (PQS) and homeostasis of proteasome, endoplasmic reticulum, and mitochondria. Important components are transcription factors (e.g., Nrf2), micro-RNAs, heat shock proteins, ionic calcium, and enzymes (e.g., glutathion redox enzymes, DNA methyltransferases, and DNA repair enzymes). Cellular growth control, intercellular communication, and resistance to stress from microbial infections involve growth factors, cytokines, chemokines, interferons, and their respective receptors. The effects of hormesis during evolution are multifarious: cell protection and survival, evolutionary flexibility, and epigenetic memory. According to the hormesis theory, this is true for the entire biosphere, e.g., archaia, bacteria, fungi, plants, and the animal kingdoms.

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Section: Discussionmentioning

confidence: 99%

Less Can Be More: The Hormesis Theory of Stress Adaptation in the Global Biosphere and Its Implications

Schirrmacher¹

2021

Biomedicines

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“…There is evidence of crosstalk between autophagy and apoptosis, 60 , 61 and a regulatory relationship between mTOR and E2F1 has been demonstrated. 62 , 63 The starting point of autophagy is regulated by mTOR, a macromolecular signaling complex that has mTORC1 and mTORC2 constituents.…”

Section: Discussionmentioning

confidence: 99%

Curcumin-Alleviated Osteoarthritic Progression in Rats Fed a High-Fat Diet by Inhibiting Apoptosis and Activating Autophagy via Modulation of MicroRNA-34a

Yao¹,

Liu²,

Sun³

et al. 2021

JIR

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Purpose The mechanism underlying curcumin’s protective effect on osteoarthritis (OA) has not been clarified. This study aimed to determine whether curcumin exerts a chondroprotective effect by inhibiting apoptosis via upregulation of E2F1/PITX1 and activation of autophagy via the Akt/mTOR pathway by targeting microRNA-34a (miR-34a). Methods Male Sprague–Dawley rats were fed a normal diet (ND) or high-fat diet (HFD) for 28 weeks. Five rats from each diet group were selected randomly for histological analysis of OA characteristics. Rats fed a HFD were given a single intra-stifle joint injection of the miR-34a mimic agomir-34a or negative control agomir (NC), followed by weekly low-dose (200 μg/kg body weight) or high-dose (400 μg/kg body weight) curcumin intra-joint injections from weeks 29 to 32. The rats’ stifle joints were submitted to histological analysis and to an apoptotic assay. Expression of miR-34a was detected using a real-time RT-PCR. E2F1 and PITX1 protein levels were determined by Western blot analysis, and the expressions of Beclin1, LC3B, p62, phosphorylated (p)-Akt, and p-mTOR were measured using immunofluorescence analysis. Results We found that rats fed a HFD had OA-like lesions in their articular cartilage and had increased apoptosis of chondrocytes and decreased autophagy compared to rats fed a ND. Curcumin treatment alleviated OA changes, inhibited apoptosis, and upregulated autophagy. Agomir-34a treatment reduced E2F1, PITX1, Beclin1, and LC3B expression and increased p62, p-Akt, and p-mTOR expression in HFD-fed rats given low- or high-dose curcumin. Greater numbers of apoptotic cells, lesser expression of p62, p-Akt, and p-mTOR, and greater expression of E2F1, PITX1, and LC3B were observed in the agomir-34a and high-dose curcumin-treated group than in agomir-34a and low-dose curcumin-treated group. Conclusion Curcumin’s chondroprotective effect was mediated by its suppression of miR-34a, apparently by reducing apoptosis, via upregulation of E2F1/PITX1, and by augmenting autophagy, likely via the Akt/mTOR pathway.

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“…Curcumin, a major active component of turmeric (Curcuma longa, L.), has anticancer, anti-inflammatory, and antioxidant effects and has been applied to cancer, atherosclerosis, and neurodegenerative diseases [118][119][120]. Low dose of curcumin induces adaptive oxidative stress responses, while high dose of curcumin induces acute responses such as autophagy and mitochondrial destabilization [121]. This phenomenon is often referred to as hormesis.…”

Section: Ros As a Link To Connect Autophagy And Antioxidant Pathwaysmentioning

confidence: 99%

Reactive Oxygen Species as a Link between Antioxidant Pathways and Autophagy

Ding

et al. 2021

Oxidative Medicine and Cellular Longevity

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Reactive oxygen species (ROS) are highly reactive molecules that can oxidize proteins, lipids, and DNA. Under physiological conditions, ROS are mainly generated in the mitochondria during aerobic metabolism. Under pathological conditions, excessive ROS disrupt cellular homeostasis. High levels of ROS result in severe oxidative damage to the cellular machinery. However, a low/mild level of ROS could serve as a signal to trigger cell survival mechanisms. To prevent and cope with oxidative damage to biomolecules, cells have developed various antioxidant and detoxifying mechanisms. Meanwhile, ROS can initiate autophagy, a process of self-clearance, which helps to reduce oxidative damage by engulfing and degrading oxidized substance. This review summarizes the interactions among ROS, autophagy, and antioxidant pathways. The effects of natural phytochemicals on autophagy induction, antioxidation, and dual-function are also discussed.

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Curcumin, a Multifaceted Hormetic Agent, Mediates an Intricate Crosstalk between Mitochondrial Turnover, Autophagy, and Apoptosis

Cited by 53 publications

References 233 publications

Less Can Be More: The Hormesis Theory of Stress Adaptation in the Global Biosphere and Its Implications

Less Can Be More: The Hormesis Theory of Stress Adaptation in the Global Biosphere and Its Implications

Curcumin-Alleviated Osteoarthritic Progression in Rats Fed a High-Fat Diet by Inhibiting Apoptosis and Activating Autophagy via Modulation of MicroRNA-34a

Reactive Oxygen Species as a Link between Antioxidant Pathways and Autophagy

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