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Apoptosis

About: Apoptosis is a research topic. Over the lifetime, 115486 publications have been published within this topic receiving 4887151 citations. The topic is also known as: GO:0006915 & apoptotic cell death.


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Journal ArticleDOI
TL;DR: The results support the conclusion that the release of cytochrome c from mitochondria resulting from Pc 4-PDT-induced photodamage is independent of the loss of Δψm.
Abstract: Photodynamic therapy (PDT) with the phthalocyanine photosensitizer Pc 4 induces rapid apoptosis in mouse lymphoma (LY-R) cells, initiating with the release of cytochrome c from mitochondria. It has been proposed that the opening of the mitochondrial membrane permeability transition pores, which results in the dissipation of the mitochondrial membrane potential (Deltapsi(m)), is essential for the escape of cytochrome c from mitochondria into the cytosol as well as for apoptotic cell death. Therefore, we have assessed the correlation between the loss of Deltapsi(m)and the release of cytochrome c following PDT. Treatment of LY-R cells with 300 nM Pc 4 and 60, 90 or 120 mJ/cm(2)of red light resulted in apoptosis of 80-90% of the cells, accompanied by >20-fold elevation in caspase-3-like activity within one h. At all 3 doses of PDT employed here, the majority of the cytochrome c was released from mitochondria at 15 min after irradiation, as determined by an immunohistochemical method. In contrast, the loss of Deltapsi(m)following PDT, as monitored by the uptake of JC-1 or Rh-123, depended on the PDT dose and the post-treatment time. In spite of the release of cytochrome c at 15 min after each of the 3 doses, a corresponding loss of Deltapsi(m)was observed only for those cells that received the highest dose of PDT. Virtually all cells that received one of the lower doses of PDT (300 nM Pc 4 plus 60 or 90 mJ/cm(2)) maintained normal Deltapsi(m). Hence, our results support the conclusion that the release of cytochrome c from mitochondria resulting from Pc 4-PDT-induced photodamage is independent of the loss of Deltapsi(m). Therefore, it is important to consider a range of doses of this or other apoptotic stimuli in deciphering the relationship of metabolic responses that contribute to apoptosis.

109 citations

Journal ArticleDOI
TL;DR: ActD-induced hepatocyte sensitization to TNF-α cytotoxicity occurs through a FADD-dependent, caspase-independent pathway of apoptosis, suggesting that NF-κB inactivation and inhibition of RNA synthesis sensitize RALA255-10G hepatocytes to TNP toxicity through distinct cell death pathways that diverge below the level of FADD.

109 citations

Journal ArticleDOI
TL;DR: These findings offer a mechanistic explanation for exercise-dependent suppression of breast cancer cell growth and suggest catecholamines were the responsible exercise factors.
Abstract: Strong epidemiologic evidence documents the protective effect of physical activity on breast cancer risk, recurrence, and mortality, but the underlying mechanisms remain to be identified. Using human exercise-conditioned serum for breast cancer cell incubation studies and murine exercise interventions, we aimed to identify exercise factors and signaling pathways involved in the exercise-dependent suppression of breast cancer. Exercise-conditioned serum from both women with breast cancer (n = 20) and healthy women (n = 7) decreased MCF-7 (hormone-sensitive) and MDA-MB-231 (hormone-insensitive) breast cancer cell viability in vitro by 11% to 19% and reduced tumorigenesis by 50% when preincubated MCF-7 breast cancer cells were inoculated into NMRI-Foxn1nu mice. This exercise-mediated suppression of cell viability and tumor formation was completely blunted by blockade of β-adrenergic signaling in MCF-7 cells, indicating that catecholamines were the responsible exercise factors. Both epinephrine (EPI) and norepinephrine (NE) could directly inhibit breast cancer cell viability, as well as tumor growth in vivo EPI and NE activate the tumor suppressor Hippo signaling pathway, and the suppressive effect of exercise-conditioned serum was found to be mediated through phosphorylation and cytoplasmic retention of YAP and reduced expression of downstream target genes, for example, ANKRD1 and CTGF. In parallel, tumor-bearing mice with access to running wheels showed reduced growth of MCF-7 (-36%, P < 0.05) and MDA-MB-231 (-66%, P < 0.01) tumors and, for the MCF-7 tumor, increased regulation of the Hippo signaling pathway. Taken together, our findings offer a mechanistic explanation for exercise-dependent suppression of breast cancer cell growth. Cancer Res; 77(18); 4894-904. ©2017 AACR.

109 citations

Journal ArticleDOI
TL;DR: It is suggested that developmental lead exposure produced rod-selective apoptosis without mitochondrial swelling by translocating cytosolic Bax to the mitochondria, which likely sensitized the Pb2+ and Ca2+ overloaded rod mitochondria to release cytochrome c.
Abstract: Photoreceptor apoptosis and resultant visual deficits occur in humans and animals with inherited and disease-, injury-, and chemical-induced retinal degeneration. A clinically relevant mouse model of progressive rod photoreceptor-selective apoptosis was produced by low-level developmental lead exposure and studied in combination with transgenic mice overexpressing Bcl-xL only in the photoreceptors. A multiparametric analysis of rod apoptosis and mitochondrial structure-function was performed. Mitochondrial cristae topography and connectivity, matrix volume, and contact sites were examined by using 3D electron tomography. Lead-induced rod-selective apoptosis was accompanied by rod Ca2+ overload, rhodopsin loss, translocation of Bax from the cytosol to the mitochondria, decreased rod mitochondrial respiration and membrane potential, mitochondrial cytochrome c release, caspase-3 activation, and an increase in the number of mitochondrial contact sites. These effects occurred without mitochondrial matrix swelling, outer membrane rupture, caspase-8 activation, or Bid cleavage. Bcl-xL overexpression completely blocked all apoptotic events, except Ca2+ overload, and maintained normal rod mitochondrial function throughout adulthood. This study presents images of mitochondrial contact sites in an in vivo apoptosis model and shows that Bcl-xL overexpression blocks increased contact sites and apoptosis. These findings extend our in vitro retinal studies with Pb2+ and Ca2+ and suggest that developmental lead exposure produced rod-selective apoptosis without mitochondrial swelling by translocating cytosolic Bax to the mitochondria, which likely sensitized the Pb2+ and Ca2+ overloaded rod mitochondria to release cytochrome c. These results have relevance for therapies in a wide variety of progressive retinal and neuronal degenerations where Ca2+ overload, lead exposure, and/or mitochondrial dysfunction occur.

109 citations

Journal Article
TL;DR: The basic concept of apoptosis is described and its relevance to skin diseases and multicellular organisms is described.
Abstract: In multicellular organisms, homeostasis is maintained by a balance between cell proliferation and cell death. Two common forms of cell death, called apoptosis and necrosis, have been described. Apoptosis, which is often equated with programmed cell death, is a physiological form of cell death that is responsible for the deletion of cells. Apoptosis is morphologically and biochemically characterized by cell shrinkage, dense chromatin condensation, cellular budding, fragmentation, rapid phagocytosis by nearby cells, and DNA fragmentation into units of approximately 200 base pairs. Apoptosis can be triggered by a wide variety of stimuli such as cytokines, hormones, drugs, and viruses, and their signal transduction tightly regulated by genes such as Bcl-2. Effector caspases are finally activated, resulting in apoptotic cell death. In the skin, there is considerable evidence that apoptosis plays an important role in the pathogenesis of a wide variety of skin diseases. In lichenoid tissue reactions, the Civatte body or colloid body is a form of apoptotic keratinocytes which is mediated by T lymphocytes via Fas-FasL interaction or through the perforin-granzyme B pathway. In several skin tumors, Bcl-2 or FasL expression is involved in the proliferation or regression of the tumors, or in the escape from immune attack by T cells. Moreover, apoptosis is also responsible for the homeostasis of skin, such as the keratinocyte differentiation and hair cycle. In this review, we describe the basic concept of apoptosis and its relevance to skin diseases.

109 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20242
202312,754
202215,476
20215,336
20206,039
20195,955