Biology of the Cell最新文献

Polycystic ovary syndrome or PCOS is an endocrine disorder in women of reproductive age. It is a diversified multi factorial disorder and diagnosis is very complicated because of its overlapping symptoms some of which are irregular menstrual cycle, acne in face, excess level of androgen (AE), insulin resistance, obesity, cardiovascular disease, mood disorder and type 2 diabetes (T2DM). PCOS may be caused by hormonal imbalance, genetic and epigenetic vulnerability, hypothalamic and ovarian troubles. PCOS is essentially hyperandrogenimia with oligo-anovulation. This review explains the abnormal regulation of autophagy related genes and proteins in different cells at various stages which leads to the genesis of PCOS. During nutrient starvation cells face stress condition, which it tries to overcome by activating its macroautophagy mechanism and by degrading the cytoplasmic material. This provides energy to the cell facilitating its survival. Downregulation of autophagy related genes in endometria has been observed in PCOS women. PCOS can be managed by maintaining proper lifestyle and medical treatment. Healthy meals and regular exercise can prevent the excessive weight and also reduce the PCOS complications. Medicines such as metformin, clomiphene, and the oral contraceptive pill can also balance the hormonal level. The imbalance in regulation of autophagy genes has been discussed with correlation to PCOS. The different management strategies for PCOS have also been summarized.

Background Information

Aquaporins are H₂O-permeable membrane protein pores. However, some aquaporins are also permeable to other substances such as CO₂. In higher plants, overexpression of such aquaporins has already led to an enhanced photosynthetic performance due to improved CO₂ mesophyll conductance. In this work, we investigated the effects of such aquaporins on unicellular photosynthetically active organisms, specifically cyanobacteria.

Results

Overexpression of aquaporins NtAQP1 or hAQP1 that might have a function to improve CO₂ membrane permeability lead to increased photosynthesis rates in the cyanobacterium Synechococcus sp. PCC7002 as concluded by the rate of evolved O₂. A shift in the Plastoquinone pool state of the cells supports our findings. Water permeable aquaporins without CO₂ permeability, such as NtPIP2;1, do not have this effect.

Conclusions and Significance

We conclude that also in single cell organisms like cyanobacteria, membrane CO₂ conductivity could be rate limiting and CO₂-porins reduce the respective membrane resistance. We could show that besides the tobacco aquaporin NtAQP1 also the human hAQP1 most likely functions as CO₂ diffusion facilitator in the photosynthesis assay.

Background

Spermatogenesis is a fundamental process crucial for male reproductive health and fertility. Exosomes, small membranous vesicles released by various cell types, have recently garnered attention for their role in intercellular communication.

Objective

This review aims to comprehensively explore the role of exosomes in regulating spermatogenesis, focusing on their involvement in testicular development and cell-to-cell communication.

Methods

A systematic examination of literature was conducted to gather relevant studies elucidating the biogenesis, composition, and functions of exosomes in the context of spermatogenesis.

Results

Exosomes play a pivotal role in orchestrating the complex signaling networks required for proper spermatogenesis. They facilitate the transfer of key regulatory molecules between different cell populations within the testes, including Sertoli cells, Leydig cells, and germ cells.

Conclusion

The emerging understanding of exosome-mediated communication sheds light on novel mechanisms underlying spermatogenesis regulation. Further research in this area holds promise for insights into male reproductive health and potential therapeutic interventions.

Background Information

The dual-specificity phosphatase 3 (DUSP3) regulates cell cycle progression, proliferation, senescence, and DNA repair pathways under genotoxic stress. This phosphatase interacts with HNRNPC protein suggesting an involvement in the regulation of HNRNPC-ribonucleoprotein complex stability. In this work, we investigate the impact of DUSP3 depletion on functions of HNRNPC aiming to suggest new roles for this enzyme.

Results

The DUSP3 knockdown results in the tyrosine hyperphosphorylation state of HNRNPC increasing its RNA binding ability. HNRNPC is present in the cytoplasm where it interacts with IRES trans-acting factors (ITAF) complex, which recruits the 40S ribosome on mRNA during protein synthesis, thus facilitating the translation of mRNAs containing IRES sequence in response to specific stimuli. In accordance with that, we found that DUSP3 is present in the 40S, monosomes and polysomes interacting with HNRNPC, just like other previously identified DUSP3 substrates/interacting partners such as PABP and NCL proteins. By downregulating DUSP3, Tyr-phosphorylated HNRNPC preferentially binds to IRES-containing mRNAs within ITAF complexes preferentially in synchronized or stressed cells, as evidenced by the higher levels of proteins such as c-MYC and XIAP, but not their mRNAs such as measured by qPCR. Under DUSP3 absence, this increased phosphorylated-HNRNPC/RNA interaction reduces HNRNPC-p53 binding in presence of RNAs releasing p53 for specialized cellular responses. Similarly, to HNRNPC, PABP physically interacts with DUSP3 in an RNA-dependent manner.

Conclusions and Significance

Overall, DUSP3 can modulate cellular responses to genotoxic stimuli at the translational level by maintaining the stability of HNRNPC-ITAF complexes and regulating the intensity and specificity of RNA interactions with RRM-domain proteins.

Background Information

Two pore channels (TPCs) are voltage-gated ion channel superfamily members that release Ca²⁺ from acidic intracellular stores and are ubiquitously present in both animals and plants. Starvation initiates multicellular development in Dictyostelium discoideum. Increased intracellular calcium levels bias Dictyostelium cells towards the stalk pathway and thus we decided to analyze the role of TPC2 in development, differentiation, and autophagy.

Results

We showed TPC2 protein localizes in lysosome-like acidic vesicles and the in situ data showed stalk cell biasness. Deletion of tpc2 showed defective and delayed development with formation of multi-tipped structures attached to a common base, while tpc2^OE cells showed faster development with numerous small-sized aggregates and wiry fruiting bodies. The tpc2^OE cells showed higher intracellular cAMP levels as compared to the tpc2⁻ cells while pinocytosis was found to be higher in the tpc2⁻ cells. Also, TPC2 regulates cell-substrate adhesion and cellular morphology. Under nutrient starvation, deletion of tpc2 reduced autophagic flux as compared to Ax2. During chimera formation, tpc2⁻ cells showed a bias towards the prestalk/stalk region while tpc2^OE cells showed a bias towards the prespore/spore region. tpc2 deficient strain exhibits aberrant cell-type patterning and loss of distinct boundary between the prestalk/prespore regions.

Conclusion

TPC2 is required for effective development and differentiation in Dictyostelium and supports autophagic cell death and cell-type patterning.

Significance

Decreased calcium due to deletion of tpc2 inhibit autophagic flux.

Background Information

The precise etiology of breast cancer is not completely understood, although women with BRCA1 gene mutations have a significantly increased risk of developing the disease. In addition, sporadic breast cancer is frequently associated with decreased BRCA1 gene expression. Growing evidence of Human papillomaviruses (HPVs) infections in breast tumors has raised the possibility of the involvement of HPVs in the pathogenesis of breast cancer. We investigated whether the effects of HPV oncoproteins E6 and E7 were influenced by the expression levels of BRCA1. HPV16E6E7 (prototype or E6D25E/E7N29S Asian variant type) were stably expressed in MDA-MB231 breast cancer cells, wild type for BRCA1, or with BRCA1 knocked down.

Results

Expression of HPV16E6E7 oncogenes did not affect BRCA1 levels and the abundance of HPV16E6E7 was not altered by BRCA1 knockdown. BRCA1 levels did not alter HPV16E6E7-dependent degradation of G1-S cell cycle proteins p53 and pRb. However, we found that the expression of G2-M cell cycle protein cyclin B1 enhanced by HPV16E6E7 was impacted by BRCA1 levels. Especially, we found the correlation between BRCA1 and cyclin B1 expression and this was also confirmed in breast cancer samples from a Thai cohort. We further demonstrated that the combination of HPV oncoproteins and low levels of BRCA1 protein appears to enhance proliferation and invasion. Transactivation activities of HPV16E6E7 on genes regulating cell proliferation and invasion (TGF-β and vimentin) were significantly increased in BRCA1-deficient cells.

Conclusions

Our results indicate that a deficiency of BRCA1 promotes the transactivation activity of HPV16E6E7 leading to increase of cell proliferation and invasion.

Significance

HPV infection appears to have the potential to enhance the aggressiveness of breast cancers, especially those deficient in BRCA1.

Background Information

Antiproliferative and apoptotic activities have been attributed to the phytosteroid diosgenin ((25R)-spirost-5-en-3β-ol; 1). It is known that combining glucose with two rhamnoses (the chacotrioside framework) linked to diosgenin increases its apoptotic activity. However, the effects of diosgenin glucosamine glycosides on different cancer cell types and cell death have not been entirely explored.

Results

This study reports the antiproliferative, cytotoxic, and apoptotic activities of diosgenin and its glycosylated derivative ((25R)-spirost-5-en-3β-yl β-D-glucopyranoside; 2). It also explores the effects of two diosgenin glucosamine derivates, diosgenin 2-acetamido-2-deoxy-β-D-glucopyranoside (3), and diosgenin 2-amino-2-deoxy-β-D-glucopyranoside hydrochloride (4), on different cancer cell lines. We found that all the compounds affected proliferative activity with minimal toxicity. In addition, all cancer cell lines showed morphological and biochemical characteristics corresponding to an apoptotic process. Apoptotic cell death was higher in all cell lines treated with compounds 2, 3 and 4 than in those treated with diosgenin. Moreover, compounds 3 and 4 induced apoptosis better than compounds 1 and 2. These results suggest that combining glucosamine with modified glucosamine attached to diosgenin has a greater apoptotic effect than diosgenin or its glycosylated derivative (compound 2). Furthermore, diosgenin and the abovementioned glycosides had a selective effect on tumour cells since the proliferative capacity of human lymphocytes, keratinocytes (HaCaT) and epithelial cells (CCD841) was not significantly affected.

Conclusions

Altogether, these results demonstrate that diosgenin glucosamine compounds exert an antiproliferative effect on cancer cell lines and induce apoptotic effects more efficiently than diosgenin alone without affecting non-tumour cells.

Significance

This study evidences the pro-apoptotic and selective activities of diosgenyl glucosamine compounds in cancer cell lines.