Apoptosis and necroptosis are complementary pathways controlled by common signalling adaptors, kinases and proteases; among these, caspase-8 (Casp8) is critical for death receptor-induced apoptosis. This caspase has also been implicated in non-apoptotic pathways that regulate Fas-associated via death domain (FADD)-dependent signalling and other less defined biological processes as diverse as innate immune signalling and myeloid or lymphoid differentiation patterns. Casp8 suppresses RIP3-RIP1 (also known as RIPK3-RIPK1) kinase complex-dependent necroptosis that follows death receptor activation as well as a RIP3-dependent, RIP1-independent necrotic pathway that has emerged as a host defence mechanism against murine cytomegalovirus. Disruption of Casp8 expression leads to embryonic lethality in mice between embryonic days 10.5 and 11.5 (ref. 7). Thus, Casp8 may naturally hold alternative RIP3-dependent death pathways in check in addition to promoting apoptosis. We find that RIP3 is responsible for the mid-gestational death of Casp8-deficient embryos. Remarkably, Casp8(-/-)Rip3(-/-) double mutant mice are viable and mature into fertile adults with a full immune complement of myeloid and lymphoid cell types. These mice seem immunocompetent but develop lymphadenopathy by four months of age marked by accumulation of abnormal T cells in the periphery, a phenotype reminiscent of mice with Fas-deficiency (lpr/lpr; also known as Fas). Thus, Casp8 contributes to homeostatic control in the adult immune system; however, RIP3 and Casp8 are together completely dispensable for mammalian development.
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http://dx.doi.org/10.1038/nature09857 | DOI Listing |
BMC Pharmacol Toxicol
January 2025
Department of Basic Sciences, Faculty of Allied Health Science, University of Sri Jayewardenepura, Nugegoda, Sri Lanka.
Background: Dermatophytes, the primary causative agents of superficial cutaneous fungal infections in humans, present a significant therapeutic challenge owing to the increasing prevalence of recurrent infections and the emergence of antifungal resistance. To address this critical gap, this study was designed to investigate the antifungal potential of 3-benzylideneindolin-2-one against dermatophytes and assess its in vivo toxicological profile using brine shrimp and zebrafish embryo models.
Methods: The antifungal activity of 3-benzylideneindolin-2-one was evaluated against 30 clinical isolates of dermatophyte species, including Trichophyton mentagrophytes, Trichophyton rubrum, Microsporum gypseum, Microsporum canis, and Epidermophyton floccosum, by determining the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) using the broth microdilution method.
MicroPubl Biol
January 2025
Department of Biological Sciences, Marquette University, Milwaukee, Wisconsin, United States.
The transgene has been widely used for evaluating germline apoptosis in . Here we observed an increase in embryonic lethality in the MD701 strain that contains the transgene and a strain that outcrossed the transgene into the N2 wild-type strain. While the outcrossed strain had a significantly lower level of embryonic lethality than MD701, it still showed significantly higher embryonic lethality than wild type.
View Article and Find Full Text PDFAnn Med Med Res
August 2024
Department of Pediatrics, Children's Foundation Research Institute at Le Bonheur Children's Hospital, University of Tennessee Health Science Center, USA.
GDP Dissociation Inhibitor 2 (GDI2) plays a crucial role in maintaining cellular homeostasis by regulating Rab GTPases involved in vesicular transport. This review highlights the importance of GDI2 in various biological processes, particularly embryonic development, apoptosis regulation, cancer, and immune responses. GDI2's essential function in embryonic development is evidenced by the embryonic lethality observed in GDI2 knockout mice.
View Article and Find Full Text PDFFree Radic Biol Med
January 2025
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada; Metabolic Disorders and Complications Program, and Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada; Laboratory of Aging and Neurodegenerative Disease (LAND), Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, USA; Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, Quebec, Canada. Electronic address:
Reactive oxygen species (ROS) are highly reactive oxygen containing molecules that are generated by normal metabolism. While ROS can cause damage to the building blocks that make up cells, these molecules can also act as intracellular signals that promote longevity. The levels of ROS within the cell can be regulated by antioxidant enzymes, such as superoxide dismutase (SOD), which converts superoxide to hydrogen peroxide.
View Article and Find Full Text PDFCell Tissue Bank
January 2025
Institute of Tissue Banking and Biomaterial Research, Atomic Energy Research Establishment (AERE), Savar, Dhaka, 1349, Bangladesh.
In the quest for an ideal wound healing material, human amniotic membrane (AM), tilapia skin collagen (TSC), and Centella asiatica (CA) have been studied separately for their healing potential. In this study, we formulated AM, TSC, and CA gel and studied their competency and wound healing efficacy in vivo. Gel was formulated using AM, TSC, CA, Carbopol 934, acrylic acid, glycerine, and triethanolamine and physicochemical properties e.
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