Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Tetsumori Yamashima
 -- 1198 2023-02-06 05:01:37 |
2 format correct
Conner Chen
Meta information modification 1198 2023-02-06 11:08:25 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Yamashima, T. Cultured Cells Exposed to Oxidative Stress. Encyclopedia. Available online: https://encyclopedia.pub/entry/40851 (accessed on 19 May 2024).
Yamashima T. Cultured Cells Exposed to Oxidative Stress. Encyclopedia. Available at: https://encyclopedia.pub/entry/40851. Accessed May 19, 2024.
Yamashima, Tetsumori. "Cultured Cells Exposed to Oxidative Stress" Encyclopedia, https://encyclopedia.pub/entry/40851 (accessed May 19, 2024).
Yamashima, T. (2023, February 06). Cultured Cells Exposed to Oxidative Stress. In Encyclopedia. https://encyclopedia.pub/entry/40851
Yamashima, Tetsumori. "Cultured Cells Exposed to Oxidative Stress." Encyclopedia. Web. 06 February, 2023.
Cultured Cells Exposed to Oxidative Stress
Edit
This entry is adapted from the peer-reviewed paper 10.3390/nu15030609

In 1972, Brunk and Ericsson found that significant amounts of lysosomal acid phosphatases leak through the ultrastructurally intact lysosomal membrane in cultured glioma cells. Subsequently, Brunk and his colleagues established the concept of lysosomal membrane permeabilization (LMP) in a series of works using cultured cells which were exposed to artificial oxidative stress. 

calpain-cathepsin hypothesis carbonylation electron microscopy

1. Introduction

Lysosomes digest, recycle, and dispose of aged/damaged organelles, macromolecules, or proteins within the cell in both physiological and pathological conditions. A limiting membrane seals off their hydrolytic enzymes and prevents leakage into the cytoplasm in order to not damage the cell. In the early 1950s, Christian de Duve and his colleagues demonstrated that the lysosomal acid phosphatase is not detectable within the fresh cell homogenates, but can be detected in large quantities after cell fractionation through the differential centrifugation method. Furthermore, with the aid of an electron microscope, they observed numerous membrane-bound, tiny organelles in the cell fraction. These findings led them to speculate that acid phosphatase must be sealed in a sac, but it may break and release its content in response to severe insults. This phantom enzyme provided de Duve a clue to the serendipitous discovery of the ‘lysosome’ [1][2][3].
In the late 1960s, considerable interest was focused on the implication of lysosomal involvement in cell degeneration and necrosis. In 1966, de Duve and Wattiaux reported the concept that lethal cell injury occurs in pathological states by the release of hydrolytic enzymes from damaged lysosomes. They suggested that it might be an early and triggering event for cell injury [4][5]. In 1972, Brunk and Ericsson found that significant amounts of lysosomal acid phosphatases leak through the ultrastructurally intact lysosomal membrane in cultured glioma cells [6]. Subsequently, Brunk and his colleagues established the concept of lysosomal membrane permeabilization (LMP) in a series of works using cultured cells which were exposed to artificial oxidative stress [7][8][9][10][11]. They thought that acid phosphatases or other lysosomal enzymes may leak through the ultrastructurally intact lysosomal membrane, but not from the rupture sites at the membrane. The concept of LMP was widely accepted thereafter [12]. Therefore, for a long time, the lysosome has been imprecisely considered a sturdy organelle that does not disintegrate until the cell is already devitalized [13]). However, in 1996, Yamashima et al. found through electron microscopy that the rupture of the lysosomal-limiting membrane associated with the extra-lysosomal release of cathepsin enzymes occurs in the programmed necrosis of hippocampal cornu Ammonis 1 (CA1) neurons of macaque monkeys a few days after transient global brain ischemia [14]. This was the first report of lysosomal rupture, because the concept of apoptosis had been prevailing in the 1990s as a mechanism of programmed cell death.
Nowadays, it is believed that a low level of cell stress causes LMP and apoptosis, whereas a high level of cell stress causes lysosomal membrane rupture and necrosis [15][16][17]. LMP was suggested to induce apoptosis by mitochondrial transmembrane potential loss or caspase activation. In contrast, lysosomal membrane rupture induces necrosis due to the extensive leakage of cathepsin enzymes [10][11][13][14][18][19][20][21][22][23]. Traditionally, necrotic cell death was considered a passive death mode, which is triggered by catastrophic events such as heat shock, ischemia, irradiation, or irreparable stress to the cell [24]. More recently, many of these ‘unregulated’ cell death events were found to be essentially ‘regulated’, and the ‘calpain-cathepsin hypothesis’ was formulated to explain the mechanism of programmed neuronal necrosis in 1998 [25].
Lipid peroxidation product 4-hydroxy-2-nonenal (hydroxynonenal) is generated during deep-frying in cooking oils and/or within biomembranes by the long-standing oxidative stress. It may be either protective or damaging to the cells, depending on its concentration [26]. For example, at low concentrations, hydroxynonenal is involved in the control of signal transduction, gene expression, cell proliferation, differentiation, and cell cycle regulation. At high concentrations, however, hydroxynonenal forms adducts with proteins, nucleic acids and membrane lipids, which leads to long-term cell disorder and tissue damage [27][28]. Lifestyle-related diseases are defined as health disorders which are linked to the way people live their life. Representative diseases that are affected by the lifestyle are chronic diseases such as Alzheimer’s disease, type 2 diabetes, nonalcoholic steatohepatitis (NASH), ischemic heart diseases, etc. Since the etiology of these lifestyle-related diseases is complex and varies among individuals, identification of the most essential causative substances is very difficult, especially if their relative effect, i.e., acute toxicity, is weak and many years are needed for the disease progression due to chronic toxicity. Deep-frying using vegetable oils is a popular culinary method used worldwide, but the high oil content is a major health concern. For example, in the United States, nearly half of potatoes produced are deep-fried and processed into chips and French fries [29]. Hydroxynonenal is recently thought to be a key factor for damaging cells of the brain, pancreas, and liver [18][23][30][31]). However, the causative substance of lifestyle-related diseases, if present, still remains unknown. Recently, Yamashima et al. reported the occurrence of lysosomal membrane rupture/permeabilization in the neurons, Langerhans islet cells, and hepatocytes of monkeys after consecutive injections of synthetic ‘hydroxynonenal’. They speculated that the ω-6 polyunsaturated fatty acid (PUFA)-peroxidation product, which is contained in deep-fried foods cooked by linoleic acid-rich cooking oils, is the most suspicious causative substance of lifestyle-related diseases [18][23][30][31].

2. Cultured Cells Exposed to Oxidative Stress

The concept of LMP was first reported half a century ago in cultured cells treated with lysosomotropic detergents [6]. However, the interest in implicating lysosomes in necrotic cell death faded during the following two decades, and, concomitantly, lysosomal involvement in necrosis has been overlooked. This is presumably because the ability of caspase inhibitor Z-Val-Ala-Asp-fmk (zVAD-fmk) to inhibit cell death was considered as proof of not “necrosis” but “apoptosis”. Furthermore, many researchers had failed to detect LMP by conventional electron microscopic observation, because the lysosomal membrane looked grossly intact [32]. So, the presence of LMP was suggested initially not by conventional electron microscopy but by immunoelectron microscopic analysis. By analyzing the cytotoxicity of oxidized low-density lipoprotein to cultured macrophages, Li et al. (1998) observed extra-lysosomal release of cathepsin D using immunoelectron microscopic analysis [33]. Similarly, by exposing the cultured myocytes of a neonatal rat heart to oxidative stress using redox cycling quinone naphthazarin, Roberg and Öllinger (1998) observed both leakage of intra-lysosomal cathepsin D into the cytoplasm and dissolution of myofilaments through immunoelectron microscopic analysis [34].
By exposing the cultured hepatocarcinoma cells to the synthetic hydroxynonenal, Seike et al. recently observed lysosomal membrane rupture using conventional electron microscopic analysis [18]. The fluorescence time-lapse imaging of the HepG2 hepatocarcinoma cell lines clearly showed a rapid loss of lysosomes (being stained orange by LysoTracker) at the early phase of cell necrosis. This is the first animation which demonstrated an implication of lysosomal rupture in the occurrence of necrotic cell death [18]. The addition of hydroxynonenal in the cultured medium induced ‘bursting’ necrosis which was closely associated with the gradual reduction and loss of lysosomes in the early phase. Hydroxynonenal induced neither apoptotic bodies nor cell blebbings, but shrinkage of both the nucleus and the cytoplasm was observed. In contrast, the addition of an anti-cancer agent, epirubicin hydrochloride, in the medium induced apoptotic cell death with the formation of cell blebbings and apoptotic bodies, but lysosomes remained intact until the final phase, just prior to the cell death. Obviously, hydroxynonenal induced lysosome-mediated necrosis, whereas epirubicin hydrochloride induced lysosome-unrelated apoptosis.

References

  1. Appelmans, F.; Wattiaux, R.; de Duve, C. Tissue fractionation studies. 5. The association of acid phosphatase with a special class of cytoplasmic granules in rat liver. Biochem. J. 1955, 59, 438–445.
  2. de Duve, C.; Pressman, B.C.; Gianetto, R.; Wattiaux, R.; Appelmans, F. Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat-liver tissue. Biochem. J. 1955, 60, 604–617.
  3. Novikoff, A.B.; Beaufay, H.; de Duve, C. Electon microscopy of lysosome-rich fractions from rat liver. J. Biophys. Biochem. Cytol. 1956, 2 (Suppl. 4), 179–184. Available online: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2229688/pdf/179.pdf. (accessed on 20 January 2022).
  4. Allison, A.C. Lysosomes. In The Biological Basis of Medicine; Bittar, E.E., Bittar, N., Eds.; Academic Press: London, UK; New York, NY, USA, 1968; Volume I, p. 209.
  5. de Duve, C.; Wattiaux, R. Functions of lysosomes. Ann. Rev. Physiol. 1966, 28, 435–492.
  6. Brunk, U.T.; Ericsson, J.L. Cytochemical evidence for the leakage of acid phosphatase through ultrastructurally intact lysosomal membranes. Histochem. J. 1972, 4, 479–491.
  7. Antunes, F.; Cadenas, E.; Brunk, U.T. Apoptosis induced by exposure to a low steady-state concentration of H2O2 is a consequence of lysosomal rupture. Biochem J. 2001, 356 Pt 2, 549–555.
  8. Brunk, U.T.; Dalen, H.; Roberg, K.; Hellquist, H.B. Photo-oxidative disruption of lysosomal membranes causes apoptosis of cultured human fibroblasts. Free Rad. Biol. Med. 1997, 23, 616–626.
  9. Brunk, U.T.; Svensson, I. Oxidative stress, growth factor starvation and Fas activation may all cause apoptosis through lysosomal leak. Redox Rep. 1999, 4, 3–11.
  10. Kågedal, K.; Zhao, M.; Svensson, I.; Brunk, U.T. Sphingosine-induced apoptosis is dependent on lysosomal proteases. Biochem. J. 2001, 359, 335–343.
  11. Li, W.; Yuan, X.; Nordgren, G.; Dalen, H.; Dubowchik, G.M.; Firestone, R.A.; Brunk, U.T. Induction of cell death by the lysosomotropic detergent MSDH. FEBS Lett. 2000, 470, 35–39.
  12. Boya, P.; Andreau, K.; Poncet, D.; Zamzami, N.; Perfettini, J.L.; Metivier, D.; Ojcius, D.M.; Jäättelä, M.; Kroemer, G. Lysosomal membrane permeabilization induces cell death in a mitochondrion-dependent fashion. J. Exp. Med. 2003, 197, 1323–1334.
  13. Terman, A.; Kurz, T.; Gustafsson, B.; Brunk, U.T. Lysosomal labilization. IUBMB Life 2006, 58, 531–539.
  14. Yamashima, T.; Saido, T.C.; Takita, M.; Miyazawa, A.; Yamano, J.; Miyakawa, A.; Nishijyo, H.; Yamashita, J.; Kawashima, S.; Ono, T.; et al. Transient brain ischaemia provokes Ca2+, PIP2 and calpain responses prior to delayed neuronal death in monkeys. Eur. J. Neurosci. 1996, 8, 1932–1944.
  15. Bursch, W. The autophagosomal-lysosomal compartment in programmed cell death. Cell Death Differ. 2001, 8, 569–581.
  16. Kirkegaard, T.; Jäättelä, M. Lysosomal involvement in cell death and cancer. Biochim. Biophys. Acta 2009, 1793, 746–754.
  17. Nylandsted, J.; Gyrd-Hansen, M.; Danielewicz, A.; Fehrenbacher, N.; Lademann, U.; Høyer-Hansen, M.; Weber, E.; Multhoff, G.; Rohde, M.; Jäättelä, M. Heat shock protein 70 promotes cell survival by inhibiting lysosomal membrane permeabilization. J. Exp. Med. 2004, 200, 425–435.
  18. Seike, T.; Boontem, P.; Kido, H.; Yanagi, M.; Yamamiya, D.; Nakagawa, H.; Yamashita, T.; Li, S.; Okada, H.; Harada, K.; et al. Hydroxynonenal causes hepatocyte death by disrupting lysosomal integrity in non-alcoholic steatohepatitis. Cell. Mol. Gastro. Hepatol. 2022, 14, 925–944.
  19. Syntichaki, P.; Xu, K.; Driscoll, M.; Tavernarakis, N. Specific aspartyl and calpain proteases are required for neurodegeneration in C. elegans. Nature 2002, 419, 939–944.
  20. Tardy, C.; Codogno, P.; Autefage, H.; Levade, T.; Andrieu-Abadie, N. Lysosomes and lysosomal proteins in cancer cell death (new players of an old struggle). Biochim. Biophys. Acta 2006, 1765, 101–125.
  21. Yamashima, T. Implication of cysteine proteases calpain, cathepsin and caspase in ischemic neuronal death of primates. Progress Neurobiol. 2000, 62, 273–295.
  22. Yamashima, T. Reconsider Alzheimer’s disease by the ‘calpain–cathepsin hypothesis’—A perspective review. Prog. Neurobiol. 2013, 105, 1–23.
  23. Yamashima, T.; Ota, T.; Mizukoshi, E.; Nakamura, H.; Yamamoto, Y.; Kikuchi, M.; Yamashita, T.; Kaneko, S. Intake of ω-6 polyunsaturated fatty acid-rich vegetable oils and risk of lifestyle diseases. Adv. Nutr. 2020, 11, 1489–1509.
  24. Firestone, R.A.; Pisano, J.M.; Bonney, R.J. Lysosomotropic agents. 1. Synthesis and cytotoxic action of lysosomotropic detergents. J. Med. Chem. 1979, 22, 1130–1133.
  25. Yamashima, T.; Kohda, Y.; Tsuchiya, K.; Ueno, T.; Yamashita, J.; Yoshioka, T.; Kominami, E. Inhibition of ischaemic hippocampal neuronal death in primates with catepsin B inhibitor CA-074: A novel strategy for neuroprotection based on `calpain-cathepsin hypothesis’. Eur. J. Neurosci. 1998, 10, 1723–1733.
  26. Bekyarova, G.; Tzaneva, M.; Bratoeva, K.; Ivanova, I.; Kotzev, A.; Hristova, M.; Krastev, D.; Kindekov, I.; Mileva, M. 4-Hydroxynonenal (HNE) and hepatic injury related to chronic oxidative stress. Biotechnol. Biotechnol. Equip. 2019, 33, 1544–1552.
  27. Humphries, K.M.; Yoo, Y.; Szweda, L.I. Inhibition of NADH-linked mitochondrial respiration by 4-hydroxy-2-nonenal. Biochemistry 1998, 37, 552–557.
  28. Lashin, O.M.; Szweda, P.A.; Szweda, L.I.; and Romani, A.M.P. Decreased complex II respiration and HNE-modified SDH subunit in diabetic heart. Free Radic. Biol. Med. 2006, 40, 886–896.
  29. Zhou, X.; Zhang, S.; Tang, Z.; Tang, J.; Takhar, P.S. Microwave frying and post-frying of French fries. Food Res. Int. 2022, 159, 111663.
  30. Boontem, P.; Yamashima, T. Hydroxynonenal causes Langerhans cell degeneration in the pancreas of Japanese macaque monkeys. PLoS ONE 2021, 16, e0245702.
  31. Yamashima, T.; Boontem, P.; Shimizu, H.; Ota, T.; Kikuchi, M.; Yamashita, T.; Mizukoshi, E.; Kaneko, S. Vegetable oil-derived ‘hydroxynonenal’ causes diverse cell death possibly leading to Alzheimer’s and related lifestyle diseases. J. Alzheimers Dis. Park. 2020, 10, 483. Available online: http://www.arimatu-clinic.com/img/20110430paper.pdf. (accessed on 1 October 2022).
  32. Aits, S.; Jäättelä, M. Lysosomal cell death at a glance. J. Cell Sci. 2013, 126, 1905–1912.
  33. Li, W.; Yuan, X.M.; Olsson, A.G.; Brunk, U.T. Uptake of oxidized LDL by macrophages results in partial lysosomal enzyme inactivation and relocation. Arterioscler. Thromb. Vasc. Biol. 1998, 18, 177–184.
  34. Roberg, K.; Öllinger, K. Oxidative stress causes relocation of the lysosomal enzyme cathepsin D with ensuing apoptosis in neonatal rat cardiomyocytes. Am. J. Pathol. 1998, 152, 1151–1156.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Nutrition & Dietetics; Psychology, Biological; Medicine, Research & Experimental
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Tetsumori Yamashima
View Times: 259
Revisions: 2 times (View History)
Update Date: 06 Feb 2023
Table of Contents
    1000/1000
    Hot Most Recent
    Feedback