Therapeutic Effect of Mongolian Medicine RuXian-I on Hyperplasia of Mammary Gland Induced by Estrogen/Progesterone through CRYAB-Promoted Apoptosis

The traditional Mongolian medicine (TMM) RuXian-I is an empirical formula specifically used for treating the hyperplasia of mammary gland (HMG) in clinic based on the principles of traditional Mongolian medicine, but the treatment mechanism is not completely clear. In this paper, we elaborated the mechanism of RuXian-I in the treatment of HMG induced by estrogen and progestogen from its toxicity and activity. Firstly, RuXian-I exhibited no toxic effect on HMG rats through no changes of body weight and food intake measurement and no pathologic changes of the organs (heart, liver, spleen, lung, and kidney) detected. Secondly, RuXian-I could decrease the increased nipple height and diameter and remarkably relieve the pathologic changes of HMG rats and also alleviate serum sex hormone levels (estradiol (E2), luteinizing hormone (LH), progesterone (P), and testosterone (T)) of HMG rats. Finally, RuXian-I could obviously inhibit the upregulation level of antiapoptotic protein CRYAB of HMG rats and promote mammary gland cell apoptosis of HMG rats via increases of promoting apoptosis protein caspases-3, 8, and 9 and Bax and tumor suppressor protein p53, decreases of antiapoptosis protein Bcl-2, and release of cytochrome c. These results suggested that RuXian-I has protective and therapeutic effects on HMG rats induced by estrogen and progestogen possibly via promoting apoptotic pathway regulated by CRYAB and is a promising agent for treating HMG.

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Binding of transferrin-iron to the plasma membrane of a lactating rabbit mammary gland cell

International Journal of Biochemistry ◽

10.1016/0020-711x(83)90205-7 ◽

1983 ◽

Vol 15 (5) ◽

pp. 755-758 ◽

Cited By ~ 10

Author(s):

Dimiter A. Moutafchiev ◽

Assia C. Shisheva ◽

Luben M. Sirakov

Keyword(s):

Plasma Membrane ◽

Mammary Gland ◽

Gland Cell ◽

Mammary Gland Cell

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Posttranslational Modification of Bcl-2 Facilitates Its Proteasome-Dependent Degradation: Molecular Characterization of the Involved Signaling Pathway

Molecular and Cellular Biology ◽

10.1128/mcb.20.5.1886-1896.2000 ◽

2000 ◽

Vol 20 (5) ◽

pp. 1886-1896 ◽

Cited By ~ 245

Author(s):

Kristin Breitschopf ◽

Judith Haendeler ◽

Philipp Malchow ◽

Andreas M. Zeiher ◽

Stefanie Dimmeler

Keyword(s):

Endothelial Cells ◽

Protein Kinase ◽

Map Kinase ◽

Specific Inhibitor ◽

26S Proteasome ◽

Apoptotic Pathway ◽

Critical Determinant ◽

Intact Cells ◽

Antiapoptotic Protein ◽

Tnf Α

ABSTRACT The ratio of proapoptotic versus antiapoptotic Bcl-2 members is a critical determinant that plays a significant role in altering susceptibility to apoptosis. Therefore, a reduction of antiapoptotic protein levels in response to proximal signal transduction events may switch on the apoptotic pathway. In endothelial cells, tumor necrosis factor alpha (TNF-α) induces dephosphorylation and subsequent ubiquitin-dependent degradation of the antiapoptotic protein Bcl-2. Here, we investigate the role of different putative phosphorylation sites to facilitate Bcl-2 degradation. Mutation of the consensus protein kinase B/Akt site or of potential protein kinase C or cyclic AMP-dependent protein kinase sites does not affect Bcl-2 stability. In contrast, inactivation of the three consensus mitogen-activated protein (MAP) kinase sites leads to a Bcl-2 protein that is ubiquitinated and subsequently degraded by the 26S proteasome. Inactivation of these sites within Bcl-2 revealed that dephosphorylation of Ser87 appears to play a major role. A Ser-to-Ala substitution at this position results in 50% degradation, whereas replacement of Thr74 with Ala leads to 25% degradation, as assessed by pulse-chase studies. We further demonstrated that incubation with TNF-α induces dephosphorylation of Ser87 of Bcl-2 in intact cells. Furthermore, MAP kinase triggers phosphorylation of Bcl-2, whereas a reduction in Bcl-2 phosphorylation was observed in the presence of MAP kinase-specific phosphatases or the MAP kinase-specific inhibitor PD98059. Moreover, we show that oxidative stress mediates TNF-α-stimulated proteolytic degradation of Bcl-2 by reducing MAP kinase activity. Taken together, these results demonstrate a direct protective role for Bcl-2 phosphorylation by MAP kinase against apoptotic challenges to endothelial cells and other cells.

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Impact of NiO2 Nanoparticles and Curcumin on Testis Torsion/Detorsion Injury: Role of miR-34 and circRNA 0001518

Galen Medical Journal ◽

10.31661/gmj.v10i0.2342 ◽

2021 ◽

Vol 10 ◽

pp. e2342

Author(s):

Shabnam Zarei Moradi ◽

Seyed Abdolhamid Angaji ◽

Mitra Salehi ◽

Mehrdad Hashemi

Keyword(s):

Ischemia Reperfusion ◽

Regulatory Elements ◽

Sperm Parameters ◽

Therapeutic Effects ◽

Gene Expressions ◽

Apoptotic Pathway ◽

Expression Ratio ◽

Testis Torsion ◽

Cellular Apoptosis ◽

Testicular Ischemia

Background: Testicular torsion is one cause of infertility without proper treatment. In this study, we investigate the effects of NiO2 nanoparticles (NPs) and curcumin on sperm parameters in rats and the expressions of genes involved in the apoptotic pathway, as well as expressions of miR-34 and circRNA 0001518. Materials and Methods: Forty-eight rats were randomly divided into eight groups: control (healthy rats), control rats that received NiO2-NPs, healthy rats that received curcumin, rats that received simultaneous NiO2-NPs and curcumin, untreated testicular ischemia/reperfusion (I/R) rats, testicular I/R rats that received NiO2-NPs, testicular I/R rats that received curcumin, and testicular I/R rats that received NiO2-NPs and curcumin. Then, sperms were extracted from the rats’ epididymides to analyze concentration, viability, morphology, and motility. The cellular apoptosis level was studied using flow cytometry. Also, Bad and Bcl-X gene expressions, as well as miR-34 and circRNA 0001518 levels were measured. Results: We observed improved sperm parameters in the testicular I/R) rats that received curcumin and NiO2-NPs. Administration of NiO2-NPs to healthy rats increased both apoptosis and the Bad/Bcl-X expression ratio. However, its administration to testicular I/R rats alone or in combination with curcumin decreased apoptosis and the Bad/Bcl-X expression ratio and increased expressions of miR-34 and circRNA 0001518. Conclusion: Administration of NiO2-NPs and curcumin, alone or in combination, can have therapeutic effects in testicular I/R conditions by altering the expressions of genes in the mitochondrial apoptotic pathway and their regulatory elements.

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Association of I131-Labeled Lactogenic Hormone with Cytoplasmic Nucleoprotein of Mammary Gland Cell.

Experimental Biology and Medicine ◽

10.3181/00379727-90-22089 ◽

1955 ◽

Vol 90 (2) ◽

pp. 531-533 ◽

Cited By ~ 1

Author(s):

W. F. Williams ◽

C. W. Turner

Keyword(s):

Mammary Gland ◽

Gland Cell ◽

Lactogenic Hormone ◽

Mammary Gland Cell

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The Vitamin E Derivative Gamma Tocotrienol Promotes Anti-Tumor Effects in Acute Myeloid Leukemia Cell Lines

Nutrients ◽

10.3390/nu11112808 ◽

2019 ◽

Vol 11 (11) ◽

pp. 2808 ◽

Cited By ~ 6

Author(s):

Ghanem ◽

Zouein ◽

Mohamad ◽

Hodroj ◽

Haykal ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Vitamin E ◽

Cell Lines ◽

Myeloid Leukemia ◽

Apoptotic Cell ◽

Leukemia Cell ◽

Therapeutic Effects ◽

Apoptotic Pathway ◽

Acute Myeloid

Acute myeloid leukemia (AML) is a blood cancer characterized by the formation of faulty defective myelogenous cells with morphological heterogeneity and cytogenic aberrations leading to a loss of their function. In an attempt to find an effective and safe AML treatment, vitamin E derivatives, including tocopherols were considered as potential anti-tumor compounds. Recently, other isoforms of vitamin E, namely tocotrienols have been proposed as potential potent anti-cancerous agents, displaying promising therapeutic effects in different cancer types. In this study we evaluated the anti-cancerous effects of γ-tocotrienol, on AML cell lines in vitro. For this purpose, AML cell lines incubated with γ-tocotrienol were examined for their viability, cell cycle status, apoptotic cell death, DNA fragmentation, production of reactive oxygen species and expression of proapoptotic proteins. Our results showed that γ-tocotrienol exhibits time and dose-dependent anti-proliferative, pro-apoptotic and antioxidant effects on U937 and KG-1 cell lines, through the upregulation of proteins involved in the intrinsic apoptotic pathway.

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Mammary gland cell content during various phases of lactation

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1962.203.5.939 ◽

1962 ◽

Vol 203 (5) ◽

pp. 939-941 ◽

Cited By ~ 9

Author(s):

Richard C. Moon

Keyword(s):

Mammary Gland ◽

Deoxyribonucleic Acid ◽

Cellular Proliferation ◽

Gland Cell ◽

Late Pregnancy ◽

Mammary Glands ◽

Lactation Period ◽

Cell Content ◽

Rat Mammary Gland ◽

Mammary Gland Cell

Deoxyribonucleic acid (DNA) was used as an index of the cellular state of the rat mammary gland in late pregnancy ( day 20) and early ( day 1), intense ( day 14), and declining ( day 28) lactation. Dams sacrificed on day 28 of lactation were provided with foster litters on day 14 postpartum to insure a strong sucking stimulus during the lactation period from days 14–28. Mammary DNA increased 57% from day 20 of pregnancy to lactation day 14, but no significant change in DNA content was evident by day 1 of lactation. A significantly lower DNA concentration was observed in mammary glands of rats sacrificed at lactation day 28 when compared with that of animals killed at day 14 of lactation. The data suggest that cellular proliferation of mammary gland continues well into lactation and that a decline in lactation may be due, in part, to a reduction in the number of milk-secreting cells.

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Activation of caspase-3 may not contribute to postresuscitation myocardial dysfunction

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00338.2008 ◽

2009 ◽

Vol 296 (4) ◽

pp. H1164-H1174 ◽

Cited By ~ 10

Author(s):

Jeejabai Radhakrishnan ◽

Iyad M. Ayoub ◽

Raúl J. Gazmuri

Keyword(s):

Cytochrome C ◽

Dna Fragmentation ◽

Rat Model ◽

Caspase 3 ◽

Myocardial Dysfunction ◽

Left Ventricular ◽

Stroke Work ◽

Protective Effects ◽

Apoptotic Pathway ◽

Apoptosis Protein

We have previously reported that postresuscitation myocardial dysfunction is accompanied by the release of cytochrome c and caspase-3 activation. We now investigated the role of caspase-3 activation by examining whether such process prompts apoptotic DNA fragmentation, whether caspase-3 inhibition attenuates myocardial dysfunction, and whether myocardial protective effects of sodium-hydrogen exchanger isoform-1 (NHE-1) inhibition involve caspase-3 inhibition using a rat model of ventricular fibrillation (VF) of closed-chest resuscitation. Resuscitation after 4 or 8 min of untreated VF caused significant reductions in left ventricular stroke work index averaging 23% of sham control rats at 4 h postresuscitation. Left ventricular dysfunction was accompanied by increases in cytosolic cytochrome c, decreases in pro- and cleaved caspase-9 fragments, increases in 17-kDa caspase-3 fragments, and increases in caspase-3 activity indicating the activation of the mitochondrial apoptotic pathway but without evidence of apoptotic DNA fragmentation. In addition, levels of heat shock protein 70 were increased and levels of X-linked inhibitor of apoptosis protein and αβ-crystallin were preserved, all of which can exert antiapoptotic effects. In a separate series, the caspase-3 inhibitor z-Asp-Glu-Val-Asp chloromethyl ketone given before the induction of VF failed to prevent postresuscitation myocardial dysfunction despite reductions in caspase-3 activity (2.3 ± 0.5 vs. 1.3 ± 0.5 pmol fluorophore AFC released·mg protein−1·min−1; P < 0.03). Treatment with the NHE-1 inhibitor cariporide had no effect on caspase-3 activity. Accordingly, in this rat model of VF and severe postresuscitation myocardial dysfunction, activation of caspase-3 did not lead to DNA fragmentation or contribute to myocardial dysfunction. Concomitant activation of intrinsic antiapoptotic mechanisms could play a protective role downstream to caspase-3 activation.

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