Caspase-2 does not play a critical role in cell death induction and bacterial clearance during Salmonella infection

Oxidative stress is one of the main causes of brain cell death in neurological disorders. The use of natural antioxidants to maintain redox homeostasis contributes to alleviating neurodegeneration. Glutamate is an excitatory neurotransmitter that plays a critical role in many brain functions. However, excessive glutamate release induces excitotoxicity and oxidative stress, leading to programmed cell death. Our study aimed to evaluate the effect of osmundacetone (OAC), isolated from Elsholtzia ciliata (Thunb.) Hylander, against glutamate-induced oxidative toxicity in HT22 hippocampal cells. The effect of OAC treatment on excess reactive oxygen species (ROS), intracellular calcium levels, chromatin condensation, apoptosis, and the expression level of oxidative stress-related proteins was evaluated. OAC showed a neuroprotective effect against glutamate toxicity at a concentration of 2 μM. By diminishing the accumulation of ROS, as well as stimulating the expression of heat shock protein 70 (HSP70) and heme oxygenase-1 (HO-1), OAC triggered the self-defense mechanism in neuronal cells. The anti-apoptotic effect of OAC was demonstrated through its inhibition of chromatin condensation, calcium accumulation, and reduction of apoptotic cells. OAC significantly suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs), including c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 kinases. Thus, OAC could be a potential agent for supportive treatment of neurodegenerative diseases.

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Caspase-2 and oxidative stress underlie the immunogenic potential of high hydrostatic pressure-induced cancer cell death

OncoImmunology ◽

10.1080/2162402x.2016.1258505 ◽

2016 ◽

Vol 6 (1) ◽

pp. e1258505 ◽

Cited By ~ 18

Author(s):

Irena Moserova ◽

Iva Truxova ◽

Abhishek D. Garg ◽

Jakub Tomala ◽

Patrizia Agostinis ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Hydrostatic Pressure ◽

Cancer Cell ◽

High Hydrostatic Pressure ◽

Cancer Cell Death ◽

Caspase 2 ◽

And Oxidative Stress

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Critical role of immunogenic cell death in cancer therapy

Science Bulletin ◽

10.1016/j.scib.2017.10.010 ◽

2017 ◽

Vol 62 (21) ◽

pp. 1427-1429 ◽

Cited By ~ 2

Author(s):

Tian Xia

Keyword(s):

Cell Death ◽

Cancer Therapy ◽

Critical Role ◽

Immunogenic Cell Death

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A Dual Role of Heme Oxygenase-1 in Cancer Cells

International Journal of Molecular Sciences ◽

10.3390/ijms20010039 ◽

2018 ◽

Vol 20 (1) ◽

pp. 39 ◽

Cited By ~ 48

Author(s):

Shih-Kai Chiang ◽

Shuen-Ei Chen ◽

Ling-Chu Chang

Keyword(s):

Cell Death ◽

Heme Oxygenase ◽

Cancer Progression ◽

Critical Role ◽

Causative Factor ◽

Protective Role ◽

Dark Side ◽

Heme Oxygenase 1 ◽

Cellular Iron

Heme oxygenase (HO)-1 is known to metabolize heme into biliverdin/bilirubin, carbon monoxide, and ferrous iron, and it has been suggested to demonstrate cytoprotective effects against various stress-related conditions. HO-1 is commonly regarded as a survival molecule, exerting an important role in cancer progression and its inhibition is considered beneficial in a number of cancers. However, increasing studies have shown a dark side of HO-1, in which HO-1 acts as a critical mediator in ferroptosis induction and plays a causative factor for the progression of several diseases. Ferroptosis is a newly identified iron- and lipid peroxidation-dependent cell death. The critical role of HO-1 in heme metabolism makes it an important candidate to mediate protective or detrimental effects via ferroptosis induction. This review summarizes the current understanding on the regulatory mechanisms of HO-1 in ferroptosis. The amount of cellular iron and reactive oxygen species (ROS) is the determinative momentum for the role of HO-1, in which excessive cellular iron and ROS tend to enforce HO-1 from a protective role to a perpetrator. Despite the dark side that is related to cell death, there is a prospective application of HO-1 to mediate ferroptosis for cancer therapy as a chemotherapeutic strategy against tumors.

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Analysis of programmed cell death in mouse fetal oocytes

Reproduction ◽

10.1530/rep-07-0141 ◽

2007 ◽

Vol 134 (2) ◽

pp. 241-252 ◽

Cited By ~ 42

Author(s):

A M Lobascio ◽

F G Klinger ◽

M L Scaldaferri ◽

D Farini ◽

M De Felici

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Specific Inhibitor ◽

Annexin V ◽

Death Process ◽

Parp Cleavage ◽

Tunel Staining ◽

Calpain Inhibitor ◽

Dna Ladder ◽

Caspase 2

We report a short-term culture system that allowsto define novel characteristic of programmed cell death (PCD) in fetal oocytes and to underscore newaspects of this process. Mouse fetal oocytes culturedin conditions allowingmeiotic prophase I progression underwent apoptotic degeneration waves as revealed by TUNEL staining. TEM observations revealed recurrent atypical apoptotic morphologies characterized by the absence of chromatin margination and nuclear fragmentation; oocytes with autophagic and necrotic features were also observed. Further characterization of oocyte death evidenced DNA ladder, Annexin V binding, PARP cleavage, and usually caspase activation (namely caspase-2). In the aim to modulate the oocyte death process, we found that the addition to the culture medium of the pancaspase inhibitors Z-VAD orcaspase-2-specific inhibitor Z-VDVAD resulted in a partial and transient prevention of this process. Oocyte death was significantly reduced by the antioxidant agent NAC and partly prevented by KL and IGF-I growth factors. Finally, oocyte apoptosis was reduced by calpain inhibitor I and increased by rapamycin after prolonged culture.These results support the notion that fetal oocytes undergo degeneration mostly by apoptosis. This process is, however, often morphologically atypical and encompasses other forms of cell death including caspase-independent apoptosis and autophagia. The observation that oocyte death occurs mainly at certain stages of meiosis and can only be attenuated by typical anti-apoptotic treatments favors the notion that it is controlled at least in part by stage-specific oocyte-autonomous meiotic checkpoints and when activated is little amenable to inhibition being the oocyte able to switch back and forth among different death pathways.

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A critical role of superoxide anion in selenite-induced mitophagic cell death

Autophagy ◽

10.4161/auto.5119 ◽

2008 ◽

Vol 4 (1) ◽

pp. 76-78 ◽

Cited By ~ 36

Author(s):

Eun Hee Kim ◽

Kyeong Sook Choi

Keyword(s):

Cell Death ◽

Superoxide Anion ◽

Critical Role

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Heme induces programmed necrosis on macrophages through autocrine TNF and ROS production

Blood ◽

10.1182/blood-2011-08-375303 ◽

2012 ◽

Vol 119 (10) ◽

pp. 2368-2375 ◽

Cited By ~ 135

Author(s):

Guilherme B. Fortes ◽

Leticia S. Alves ◽

Rosane de Oliveira ◽

Fabianno F. Dutra ◽

Danielle Rodrigues ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Critical Role ◽

Membrane Integrity ◽

Iron Chelation ◽

Heme Oxygenase 1 ◽

Cytotoxic Effects ◽

Interacting Protein ◽

Free Heme ◽

Necrosis Factor

Abstract Diseases that cause hemolysis or myonecrosis lead to the leakage of large amounts of heme proteins. Free heme has proinflammatory and cytotoxic effects. Heme induces TLR4-dependent production of tumor necrosis factor (TNF), whereas heme cytotoxicity has been attributed to its ability to intercalate into cell membranes and cause oxidative stress. We show that heme caused early macrophage death characterized by the loss of plasma membrane integrity and morphologic features resembling necrosis. Heme-induced cell death required TNFR1 and TLR4/MyD88-dependent TNF production. Addition of TNF to Tlr4−/− or to Myd88−/− macrophages restored heme-induced cell death. The use of necrostatin-1, a selective inhibitor of receptor-interacting protein 1 (RIP1, also known as RIPK1), or cells deficient in Rip1 or Rip3 revealed a critical role for RIP proteins in heme-induced cell death. Serum, antioxidants, iron chelation, or inhibition of c-Jun N-terminal kinase (JNK) ameliorated heme-induced oxidative burst and blocked macrophage cell death. Macrophages from heme oxygenase-1 deficient mice (Hmox1−/−) had increased oxidative stress and were more sensitive to heme. Taken together, these results revealed that heme induces macrophage necrosis through 2 synergistic mechanisms: TLR4/Myd88-dependent expression of TNF and TLR4-independent generation of ROS.

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