Cathepsin D gene expression outlines the areas of physiological cell death during embryonic development

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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Faculty Opinions recommendation of Role of Atg5-dependent cell death in the embryonic development of Bax/Bak double-knockout mice.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727681479.793532876 ◽

2017 ◽

Author(s):

Sharad Kumar ◽

Donna Denton

Keyword(s):

Cell Death ◽

Embryonic Development ◽

Knockout Mice ◽

Double Knockout ◽

Dependent Cell

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Reverse Screening Bioinformatics Approach to Identify Potential Anti Breast Cancer Targets Using Thymoquinone from Neutraceuticals Black Cumin Oil

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190124155359 ◽

2019 ◽

Vol 19 (5) ◽

pp. 599-609 ◽

Cited By ~ 1

Author(s):

Sumathi Sundaravadivelu ◽

Sonia K. Raj ◽

Banupriya S. Kumar ◽

Poornima Arumugamand ◽

Padma P. Ragunathan

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cell Cycle ◽

Cell Death ◽

In Silico ◽

Chemotherapeutic Agents ◽

Normal Cells ◽

Black Cumin ◽

In Silico Docking ◽

Wide Range

Background: Functional foods, neutraceuticals and natural antioxidants have established their potential roles in the protection of human health and diseases. Thymoquinone (TQ), the main bioactive component of Nigella sativa seeds (black cumin seeds), a plant derived neutraceutical was used by ancient Egyptians because of their ability to cure a variety of health conditions and used as a dietary food supplement. Owing to its multi targeting nature, TQ interferes with a wide range of tumorigenic processes and counteracts carcinogenesis, malignant growth, invasion, migration, and angiogenesis. Additionally, TQ can specifically sensitize tumor cells towards conventional cancer treatments (e.g., radiotherapy, chemotherapy, and immunotherapy) and simultaneously minimize therapy-associated toxic effects in normal cells besides being cost effective and safe. TQ was found to play a protective role when given along with chemotherapeutic agents to normal cells. Methods: In the present study, reverse in silico docking approach was used to search for potential molecular targets for cancer therapy. Various metastatic and apoptotic targets were docked with the target ligand. TQ was also tested for its anticancer activities for its ability to cause cell death, arrest cell cycle and ability to inhibit PARP gene expression. Results: In silico docking studies showed that TQ effectively docked metastatic targets MMPs and other apoptotic and cell proliferation targets EGFR. They were able to bring about cell death mediated by apoptosis, cell cycle arrest in the late apoptotic stage and induce DNA damage too. TQ effectively down regulated PARP gene expression which can lead to enhanced cancer cell death. Conclusion: Thymoquinone a neutraceutical can be employed as a new therapeutic agent to target triple negative breast cancer which is otherwise difficult to treat as there are no receptors on them. Can be employed along with standard chemotherapeutic drugs to treat breast cancer as a combinatorial therapy.

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Programmed cell death 4 and BCR-ABL fusion gene expression are negatively correlated in chronic myeloid leukemia

Oncology Letters ◽

10.3892/ol.2016.4942 ◽

2016 ◽

Vol 12 (4) ◽

pp. 2976-2981 ◽

Cited By ~ 2

Author(s):

Xia Zhang ◽

Riming Liu ◽

Baohua Huang ◽

Xiaolu Zhang ◽

Weijuan Yu ◽

...

Keyword(s):

Gene Expression ◽

Cell Death ◽

Chronic Myeloid Leukemia ◽

Programmed Cell Death ◽

Myeloid Leukemia ◽

Fusion Gene ◽

Programmed Cell Death 4

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Molecular pathology associated with altered synaptic transcriptome in the dorsolateral prefrontal cortex of depressed subjects

Translational Psychiatry ◽

10.1038/s41398-020-01159-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yuta Yoshino ◽

Bhaskar Roy ◽

Nilesh Kumar ◽

M. Shahid Mukhtar ◽

Yogesh Dwivedi

Keyword(s):

Gene Expression ◽

Cell Death ◽

Prefrontal Cortex ◽

Dorsolateral Prefrontal Cortex ◽

Gene Network ◽

Nervous System Development ◽

Network Analyses ◽

Dorsolateral Prefrontal ◽

Total Fraction ◽

Transcriptomic Changes

AbstractDisrupted synaptic plasticity is the hallmark of major depressive disorder (MDD), with accompanying changes at the molecular and cellular levels. Often, the maladaptive molecular changes at the synapse are the result of global transcriptional reprogramming dictated by activity-dependent synaptic modulation. Thus far, no study has directly studied the transcriptome-wide expression changes locally at the synapse in MDD brain. Here, we have examined altered synaptic transcriptomics and their functional relevance in MDD with a focus on the dorsolateral prefrontal cortex (dlPFC). RNA was isolated from total fraction and purified synaptosomes of dlPFC from well-matched 15 non-psychiatric controls and 15 MDD subjects. Transcriptomic changes in synaptic and total fractions were detected by next-generation RNA-sequencing (NGS) and analyzed independently. The ratio of synaptic/total fraction was estimated to evaluate a shift in gene expression ratio in MDD subjects. Bioinformatics and network analyses were used to determine the biological relevance of transcriptomic changes in both total and synaptic fractions based on gene–gene network, gene ontology (GO), and pathway prediction algorithms. A total of 14,005 genes were detected in total fraction. A total of 104 genes were differentially regulated (73 upregulated and 31 downregulated) in MDD group based on 1.3-fold change threshold and p < 0.05 criteria. In synaptosomes, out of 13,236 detectable genes, 234 were upregulated and 60 were downregulated (>1.3-fold, p < 0.05). Several of these altered genes were validated independently by a quantitative polymerase chain reaction (qPCR). GO revealed an association with immune system processes and cell death. Moreover, a cluster of genes belonged to the nervous system development, and psychological disorders were discovered using gene–gene network analysis. The ratio of synaptic/total fraction showed a shift in expression of 119 genes in MDD subjects, which were primarily associated with neuroinflammation, interleukin signaling, and cell death. Our results suggest not only large-scale gene expression changes in synaptosomes, but also a shift in the expression of genes from total to synaptic fractions of dlPFC of MDD subjects with their potential role in immunomodulation and cell death. Our findings provide new insights into the understanding of transcriptomic regulation at the synapse and their possible role in MDD pathogenesis.

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Apolipoprotein B-related gene expression and ultrastructural characteristics of lipoprotein secretion in mouse yolk sac during embryonic development

The Journal of Lipid Research ◽

10.1016/s0022-2275(20)32420-2 ◽

1999 ◽

Vol 40 (11) ◽

pp. 1967-1977 ◽

Cited By ~ 7

Author(s):

Yuko Terasawa ◽

Sylvaine J. Cases ◽

Jinny S. Wong ◽

Haris Jamil ◽

Sumana Jothi ◽

...

Keyword(s):

Gene Expression ◽

Embryonic Development ◽

Apolipoprotein B ◽

Yolk Sac ◽

Related Gene ◽

Lipoprotein Secretion ◽

Ultrastructural Characteristics

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Impact of the acidic environment on gene expression and functional parameters of tumors in vitro and in vivo

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-020-01815-4 ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Mandy Rauschner ◽

Luisa Lange ◽

Thea Hüsing ◽

Sarah Reime ◽

Alexander Nolze ◽

...

Keyword(s):

Gene Expression ◽

Cell Death ◽

Western Blot ◽

Tumor Cell ◽

Low Ph ◽

Strong Increase ◽

Acidic Ph ◽

The Impact

Abstract Background The low extracellular pH (pHe) of tumors resulting from glycolytic metabolism is a stress factor for the cells independent from concomitant hypoxia. The aim of the study was to analyze the impact of acidic pHe on gene expression on mRNA and protein level in two experimental tumor lines in vitro and in vivo and were compared to hypoxic conditions as well as combined acidosis+hypoxia. Methods Gene expression was analyzed in AT1 prostate and Walker-256 mammary carcinoma of the rat by Next Generation Sequencing (NGS), qPCR and Western blot. In addition, the impact of acidosis on tumor cell migration, adhesion, proliferation, cell death and mitochondrial activity was analyzed. Results NGS analyses revealed that 147 genes were uniformly regulated in both cell lines (in vitro) and 79 genes in both experimental tumors after 24 h at low pH. A subset of 25 genes was re-evaluated by qPCR and Western blot. Low pH consistently upregulated Aox1, Gls2, Gstp1, Ikbke, Per3, Pink1, Tlr5, Txnip, Ypel3 or downregulated Acat2, Brip1, Clspn, Dnajc25, Ercc6l, Mmd, Rif1, Zmpste24 whereas hypoxia alone led to a downregulation of most of the genes. Direct incubation at low pH reduced tumor cell adhesion whereas acidic pre-incubation increased the adhesive potential. In both tumor lines acidosis induced a G1-arrest (in vivo) of the cell cycle and a strong increase in necrotic cell death (but not in apoptosis). The mitochondrial O2 consumption increased gradually with decreasing pH. Conclusions These data show that acidic pHe in tumors plays an important role for gene expression independently from hypoxia. In parallel, acidosis modulates functional properties of tumors relevant for their malignant potential and which might be the result of pH-dependent gene expression.

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