ArticleThe American journal of pathology2000
Studies on the mechanisms and kinetics of apoptosis induced by microinjection of cytochrome c in rat kidney tubule epithelial cells (NRK-52E).
Article in The American journal of pathology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 51 citations in OpenAlex.
- Neuronal Apoptotic Bodies Facilitate Japanese Encephalitis Virus Infection and Pathogenicity.Journal of extracellular vesicles · 2026Article
- Anticancer Nanoparticle Carriers of the Proapoptotic Protein CytochromePharmaceutics · 2025Review
- Unravelling oncosis: morphological and molecular insights into a unique cell death pathway.Frontiers in immunology · 2024Review
- Apoptotic volume decrease (AVD) in AFrontiers in physiology · 2023Article
- Concentration Dependence of the Antioxidant and Prooxidant Activity of Trolox in HeLa Cells: Involvement in the Induction of Apoptotic Volume Decrease.Antioxidants (Basel, Switzerland) · 2020Article
- Dahuang Zhechong Pill Combined with Doxorubicin Induces Cell Death through Regulating Energy Metabolism in Human Hepatocellular Carcinoma Cells.Evidence-based complementary and alternative medicine : eCAM · 2017Article
- Mechanisms of acute kidney injury induced by experimental Lonomia obliqua envenomation.Archives of toxicology · 2015Article
- Sevoflurane post-conditioning protects isolated rat hearts against ischemia-reperfusion injury via activation of the ERK1/2 pathway.Acta pharmacologica Sinica · 2014Article
- K+ channels in apoptosis.The Journal of membrane biology · 2006Review
- Reduced Apaf-1 levels in cardiomyocytes engage strict regulation of apoptosis by endogenous XIAP.The Journal of cell biology · 2005Article
- Identification of thrombospondin 1 (TSP-1) as a novel mediator of cell injury in kidney ischemia.The Journal of clinical investigation · 2005Article
- Decreased apoptosome activity with neuronal differentiation sets the threshold for strict IAP regulation of apoptosis.The Journal of cell biology · 2004Article
- Regulation of apoptosis by endoplasmic reticulum pathways.Oncogene · 2003Review
- Critical function of endogenous XIAP in regulating caspase activation during sympathetic neuronal apoptosis.The Journal of cell biology · 2003Article
- Analysis of retinal pigment epithelium integrin expression and adhesion to aged submacular human Bruch's membrane.Transactions of the American Ophthalmological Society · 2003Article
- Studies on neuronal apoptosis in primary forebrain cultures: neuroprotective/anti-apoptotic action of NR2B NMDA antagonists.Neurotoxicity research · 2003Article
- Exogenous smac induces competence and permits caspase activation in sympathetic neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2002Article
- Microinjection of cathepsin d induces caspase-dependent apoptosis in fibroblasts.The American journal of pathology · 2002Article
- Dynamic process of apoptosis in adult rat cardiomyocytes analyzed using 48-hour videomicroscopy and electron microscopy: beating and rate are associated with the apoptotic process.The American journal of pathology · 2001Article
- Receptor-mediated control of regulatory volume decrease (RVD) and apoptotic volume decrease (AVD).The Journal of physiology · 2001Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Recent reports substantiating the role of cytochrome c in the induction of apoptosis led us to examine the kinetics and mechanisms involved in this process as an extension of our ongoing studies of cell injury and cell death. Microinjection of cytochrome c into NRK-52E kidney cells produced rapid apoptosis, which usually began within 30 minutes and reached a maximum of 60-70% by 3 hours. The changes that occurred included four phases: an initial shrinkage phase, an active phase, a spherical phase, and a necrotic phase. For morphological purposes, the progressive changes were followed by phase-contrast and fluorescence microscopy, transmission and scanning electron microscopy, and time-lapse video microscopy. Cells first showed shrinkage, then displayed multiple pseudopods, which rapidly extended and retracted, giving the cells a bosselated appearance. During this active phase there was chromatin condensation, mitochondria were swollen but retained membrane potential, and the endoplasmic reticulum was dilated. Within 2-4 hours, active-phase cells became spherical and smooth-surfaced but were still alive, the nuclei showed chromatin clumping, the mitochondria underwent high-amplitude swelling but retained membrane potential, the endoplasmic reticulum was highly dilated, and many large apical vacuoles were present. Elevation of [Ca(2+)](i) was seen at the late spherical phase, shortly before cell death. Pretreatment with the caspase 3 inhibitor (Ac-DEVD-CHO) prevented apoptosis, whereas overexpression of Bcl-2 did not. Depletion of cellular ATP by cyanide inhibition of energy metabolism prevented cytochrome c from inducing the active and later phases of apoptosis. The results clearly indicate that cytochrome c-induced apoptosis is a dynamic and energy-requiring process that has a distinct active and spherical phase before cell death.
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