The Molecular and Genetic Effects of Ultraviolet Radiation Exposure on Skin Cells
Henry W. Lim, Herbert Hönigsmann, John L. M. Hawk in Photodermatology, 2007
The apoptotic process itself is characterized by stereotypical morphological changes such as cell shrinkage, membrane blebbing, chromatin condensation, and DNA fragmentation, leading to a cell with a pycnotic nucleus, and ultimately the formation of apoptotic bodies. Hence, when skin is irradiated with a sufficient high UVB dose, cells with pycnotic nucleus and eosinophilic cytoplasm, a typical apoptotic morphology, also called “the sunburn cell” (SBC), appear in the epidermis. At the biochemical level, the induction of apoptotic cell death is accomplished by specialized cellular machinery where a family of cysteine proteases, the caspases, play a central role. There are two main pathways leading to apoptotic cell death. The intrinsic pathway is activated at the mitochondria. Death-inducing signals (including DNA damage) promote BAX-dependent release of cytochrome C, which together with Apaf- 1 leads to formation of the apoptosome and procaspase 9 activation. In contrast, signaling through the cell surface death receptor (e.g., CD95/Fas, TNF-alphaR) activates the extrinsic pathway, which relies on initiator caspase-8 activation at the death-inducing signaling complex. Both pathways converge into the activation of the effector caspases (caspases-3, -6, and -7) that are directly responsible for the cleavage of cellular proteins resulting in the characteristic morphology of apoptosis. Cleavage of Bid by caspase-8 allows crosstalk between both pathways.
A Review on Medicinal Plants used in Cardioprotective Remedies in Traditional Medicine
Anne George, Oluwatobi Samuel Oluwafemi, Blessy Joseph, Sabu Thomas, Sebastian Mathew, V. Raji in Holistic Healthcare, 2017
The in vitro and in vivo studies have suggested that DOX induce cardiac toxicity through apoptosis, necrosis and other form of cell death called autophagy. DOX treatment induces apoptosis via an intrinsic and extrinsic pathway. In the extrinsic pathway; caspase 8 was activated by binding of death ligands (FasL, TNF-a, and TRAIL) with their receptors leads to subsequent activation of caspase 3, which results in cell death. The intrinsic pathway is mediated by mitochondrial cytochrome c release (Table 11.4). The cytochrome c forms a complex called apoptosome with the adaptor protein apoptosis protease activator protein-1 (Apaf-1), dATP, and caspase 9 in cytosol. This apoptosome activates caspase 9 results in DNA fragmentation.50 Recent studies have shown that DOX treatment significantly increased the cardiac expression of pro-inflammatory cytokine, inflammatory cell infiltration, and necrosis in rat hearts. The increased generation of ROS leads to mitochondrial calcium accumulation, promotes MPT pore opening, causes mitochondrial swelling and ATP depletion, and hence triggers necrotic cell death.51,52
Applied physiology: neuropathic pain
Peter R Wilson, Paul J Watson, Jennifer A Haythornthwaite, Troels S Jensen in Clinical Pain Management, 2008
Many forms of nerve injury can also produce death of sensory neurons.96 Apoptosis may be a result of mitochondrial dysfunction97 and has been associated with a number of neuropathies.96,98,99 Mitochondria-dependent apoptosis is activated by a number of factors including reactive oxygen species, ceramide, and nitric oxide,100 which have been implicated in the pathophysiology of neuropathies. These factors cause the release of cytochrome C from mitochondria leading to the formation of the apoptosome complex and subsequent activation of effector caspases. Alternatively, apoptotic pathways can be activated via stimulation of death receptors, such as TNFR1100 which can act via the JNK (c-Jun-N-terminal kinase) pathway to activate effector caspases. In support of this, TNFa is released in response to chemotherapeutic agents that produce painful peripheral neuropathy,101 following direct nerve injury,102 and in response to HIV-gp120 in vitro103 and caspases have been shown to be important in neuropathic responses in various models of neuropathy.20,96,104,105 It is thought that the activation of these pathways may be involved in neuropathic pain even though there may be a prolonged latent phase of apoptosis, before cell death.
Sevelamer arsenite nanoparticle as a Pi-responsive drug carrier and embolic agent for chemoembolization
Published in Drug Delivery, 2022
Qiu-Chen Bi, Jian-Jun Tang, Jun Zhao, Yang-Feng Lv, Zhi-Qiang Deng, Hong Chen, Yu-Hua Xu, Chuan-Sheng Xie, Qing-Rong Liang, Rong-Guang Luo, Qun Tang
Pi deprivation enhances HCC’s sensitivity to anticancer ATO, as we evidenced both in vivo and in vitro tests. Although the mechanism for the enhancement is complex, Pi-triggered apoptosis has been evidenced. Cellular apoptosis can be triggered by the mitochondrial-apoptosome-mediated intrinsic pathway. Pi deprivation stress-induced mitochondrial transmembrane potential drop-down, resulting in higher membrane permeability and cytochrome c release. The released cytochrome c from mitochondria activates caspase-9, eventually initiating caspase cascade reaction and apoptosis, as rationalized by the theory (Hengartner, 2000; Frion-Herrera et al., 2015). The promoter of apoptosis has been proved to sensitize the killing effect of ATO (Szegezdi et al., 2006; Chen et al., 2017).
Effect of chronic alcohol consumption on myocardial apoptosis in the rat model of isoproterenol-induced myocardial injury and investigation on the cardioprotective role of calpain inhibitor 1
Published in Drug and Chemical Toxicology, 2022
Aysegul Oglakci-Ilhan, Kevser Kusat-Ol, Kubilay Uzuner, Onur Uysal, Ibrahim Sogut, Ferruh Yucel, Gungor Kanbak
High-dose chronic alcohol consumption causes mitochondrial dysfunction, apoptosis, increased reactive oxygen species production, and cellular ATP loss (Bansal et al. 2012). The primary and essential step that initiates the apoptotic pathway is cytochrome c release from mitochondria. Cytochrome c released into the cytosol forms the apoptosome with a protein called Apaf-1 and procaspase 9. Apoptosome activates caspase-9, and this activates caspase-3. Caspase 3 migrates to the nucleus causing DNA fragmentation and cell death there. Cytochrome c is bound to the inner membrane by cardiolipin, an anionic phospholipid. For the release of cytochrome c from mitochondria, it must first be separated from cardiolipin. Cardiolipin peroxidation enables cytochrome c to be released from the inner membrane (Gonzalvez and Gottlieb 2007).
Apoptotic resistance in chronic lymphocytic leukemia and therapeutic perspectives
Published in Critical Reviews in Clinical Laboratory Sciences, 2019
Cristina Bagacean, Ciprian Tomuleasa, Adrian Tempescul, Ravnit Grewal, Wesley H. Brooks, Christian Berthou, Yves Renaudineau
Acting as an integrator of the cellular response to DNA damage, tumor transformation, and growth factor withdrawal, the tumor suppressor p53 is a main cellular guardian that can promote the execution of the intrinsic apoptotic pathway, cell growth arrest, and DNA repair. Under normal conditions, p53 is a short-lived protein that needs to be stabilized to be active, and then its half-life shifts from minutes (6–20 min) to hours. p53, via the intrinsic pathway, promotes apoptosis through (i) transcription of the pro-apoptotic genes Puma, Noxa, Bax; (ii) transcription of the apoptosome partner, Apaf-1; and (iii), MOMP, by acting directly in mitochondria by forming complexes with Bcl-2 and Bcl-XL, which allows Bak activation by releasing Bid and Bim in a direct and transcriptional independent manner [16].
Related Knowledge Centers
- Apaf1
- Cytochrome C
- DNA Repair
- Protein
- Transmission Electron Microscopy
- Apoptosis
- Mitochondrion
- Viral Disease
- Deoxyadenosine Triphosphate
- Cryogenic Electron Microscopy