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In women, up to 99.9% of the oocyte stockpile formed during fetal life is decimated by apoptosis. Apoptotic features are also detected in human preimplantation embryos both in vivo and in vitro. Despite the important consequences of cell death processes to oocyte competence and early embryonic development, little is known about its genetic and molecular control. B cell lymphoma-2 (BCL2) family proteins are major regulators of cell death and survival. Here, we present a literature review on BCL2 family expression and protein distribution in human and animal oocytes and early embryos. Most of the studies focused on the expression of two antagonistic members: the founding and survival family member BCL2 and its proapoptotic homolog BAX. However, recent transcriptomic analyses have identified novel candidate genes related to oocyte and/or early embryonic viability (such as BCL2L10) or commitment to apoptosis (e.g. BIK). Interestingly, some BCL2 proteins appear to be differentially distributed at the subcellular level during oocyte maturation and early embryonic development, a process probably linked to the functional compartmentalization of the ooplasm and blastomere. Assessment of BCL2 family involvement in regulating the survival of human oocytes and embryos may be of particular value for diagnosis and assisted reproductive technology. We suggest that implications of not only aberrant gene expression but also abnormal subcellular protein redistribution should be established in pathological conditions resulting in infertility.
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http://dx.doi.org/10.1530/REP-10-0504 | DOI Listing |
Oncol Rep
February 2025
Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467‑8601, Japan.
BH3 mimetics are small‑molecule inhibitors of the antiapoptotic Bcl‑2 family and have therapeutic efficacy against hematological malignancies. BH3 mimetic A‑1331852 suppresses colorectal cancer cell proliferation. Progressive resistance to the widely used anticancer agent fluorouracil (5‑FU) is a key reason for colorectal cancer recurrence; therefore, the present study tested if A‑1331852 can suppress the proliferation of 5‑FU‑resistant colorectal cancer cells.
View Article and Find Full Text PDFCell Death Dis
December 2024
University of Zürich, Institute of Anatomy, Winterthurerstrasse 190, 8057, Zürich, Switzerland.
The TGFβ signaling pathway is known for its pleiotropic functions in a plethora of biological processes. In melanoma, TGFβ signaling promotes invasiveness and metastasis formation. However, its involvement in the response to therapy is controversial.
View Article and Find Full Text PDFBiochem Pharmacol
December 2024
Zhongshan Hospital Institute of Clinical Science, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address:
B-cell lymphoma extra large (BCL-X) is an important anti-apoptotic protein of BCL-2 family. It is frequently overexpressed in various hematologic and solid tumors, often positively correlated with chemotherapy resistance in tumors. However, the clinical development of the small molecule BCL-X inhibitor ABT-263 has been challenged on account of its on-target and dose-limiting toxicity.
View Article and Find Full Text PDFEur J Med Chem
December 2024
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address:
Myeloid cell leukemia-1 (MCL-1), a key anti-apoptotic protein within the BCL-2 family, is essential in regulating cell survival, particularly in cancer, where its overexpression is often linked to therapeutic resistance. This review begins with an overview of BCL-2-mediated apoptosis, highlighting the pivotal role of MCL-1 in cellular homeostasis. We then focus on the structure and function of MCL-1, elucidating how its unique structural features contribute to its function and interaction with pro-apoptotic proteins.
View Article and Find Full Text PDFInt J Immunopathol Pharmacol
December 2024
Department of Rehabilitation Medicine, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, P. R. China.
We explored the biological mechanisms by which curcumin (Cur) confronts osteosarcoma (OS) tumorigenesis and potential drug gene targets based on network pharmacology and in vitro cell experiments. Cur has been recognized for its significant role in combating various types of tumors. However, the intrinsic molecular mechanisms through which it affects OS remain uncharted.
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