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Sichuan Da Xue Xue Bao. Yi Xue Ban =... May 2024Kisspeptin, a protein encoded by the gene, functions as an essential factor in suppressing tumor growth. The intricate orchestration of cellular processes such as...
OBJECTIVE
Kisspeptin, a protein encoded by the gene, functions as an essential factor in suppressing tumor growth. The intricate orchestration of cellular processes such as proliferation and differentiation is governed by the Notch1/Akt/Foxo1 signaling pathway, which assumes a central role in maintaining cellular homeostasis. In the specific context of this investigation, the focal point lies in a meticulous exploration of the intricate mechanisms underlying the regulatory effect of kisspeptin on the process of endometrial decidualization. This investigation delves into the interplay between kisspeptin and the Notch1/Akt/Foxo1 signaling pathway, aiming to elucidate its significance in the pathophysiology of recurrent spontaneous abortion (RSA).
METHODS
We enrolled a cohort comprising 45 individuals diagnosed with RSA, who were admitted to the outpatient clinic of the Reproductive Center at the Second Affiliated Hospital of Soochow University between June 2020 and December 2020. On the other hand, an additional group of 50 women undergoing elective abortion at the outpatient clinic of the Family Planning Department during the same timeframe was also included. To comprehensively assess the molecular landscape, Western blot and RT-qPCR were performed to analyze the expression levels of kisspeptin (and its gene ), IGFBP1 (an established marker of decidualization), Notch1, Akt, and Foxo1 within the decidua. Human endometrial stromal cells (hESC) were given targeted interventions, including treatment with siRNA to disrupt or exposure to kisspeptin10 (the bioactive fragment of kisspeptin), and were subsequently designated as the siKP group or the KP10 group, respectively. A control group comprised hESC was transfected with blank siRNA, and cell proliferation was meticulously evaluated with CCK8 assay. Following induction for decidualization across the three experimental groups, immunofluorescence assay was performed to identify differences in Notch1 expression and decidualization morphology between the siKP and the KP10 groups. Furthermore, RT-qPCR and Western blot were performed to gauge the expression levels of IGFBP1, Notch1, Akt, and Foxo1 across the three cell groups. Subsequently, decidualization was induced in hESC by adding inhibitors targeting Notch1, Akt, and Foxo1. The expression profiles of the aforementioned proteins and genes in the four groups were then examined, with hESC induced for decidualization without adding inhibitors serving as the normal control group. To establish murine models of normal pregnancy (NP) and RSA, CBA/J×BALB/c and CBA/J×DBA/2 mice were used. The mice were respectively labeled as the NP model and RSA model. The experimental groups received intraperitoneal injections of kisspeptin10 and kisspeptin234 (acting as a blocker) and were designated as RSA-KP10 and NP-KP234 groups. On the other hand, the control groups received intraperitoneal injections of normal saline (NS) and were referred to as RSA-NS and NP-NS groups. Each group comprised 6 mice, and uterine tissues from embryos at 9.5 days of gestation were meticulously collected for observation of embryo absorption and examination of the expression of the aforementioned proteins and genes.
RESULTS
The analysis revealed that the expression levels of kisspeptin, IGFBP1, Notch1, Akt, and Foxo1 were significantly lower in patients diagnosed with RSA compared to those in women with NP (<0.01 for kisspeptin and <0.05 for IGFBP1, Notch1, Akt, and Foxo1). After the introduction of kisspeptin10 to hESC, there was an observed enhancement in decidualization capability. Subsequently, the expression levels of Notch1, Akt, and Foxo1 showed an increase, but they decreased after interference with . Through immunofluorescence analysis, it was observed that proliferative hESC displayed a slender morphology, but they transitioned to a rounder and larger morphology post-decidualization. Concurrently, the expression of Notch1 increased, suggesting enhanced decidualization upon the administration of kisspeptin10, but the expression decreased after interference with . Further experimentation involved treating hESC with inhibitors specific to Notch1, Akt, and Foxo1 separately, revealing a regulatory sequence of Notch1/Akt/Foxo1 (<0.05). In comparison to the NS group, NP mice administered with kisspeptin234 exhibited increased fetal absorption rates (<0.001) and decreased expression of IGFBP1, Notch1, Akt, and Foxo1 (<0.05). Conversely, RSA mice administered with kisspeptin10 demonstrated decreased fetal absorption rates (<0.001) and increased expression levels of the aforementioned molecules (<0.05).
CONCLUSION
It is suggested that kisspeptin might exert its regulatory influence on the process of decidualization through the modulation of the Notch1/Akt/Foxo1 signaling cascade. A down-regulation of the expression levels of kisspeptin could result in suboptimal decidualization, which in turn might contribute to the development or progression of RSA.
Topics: Female; Forkhead Box Protein O1; Humans; Proto-Oncogene Proteins c-akt; Endometrium; Signal Transduction; Decidua; Pregnancy; Receptor, Notch1; Abortion, Habitual; Kisspeptins; Adult; Insulin-Like Growth Factor Binding Protein 1; Cell Proliferation
PubMed: 38948287
DOI: 10.12182/20240560206 -
PeerJ 2024PLAUR has been found upregulated in various tumors and closely correlated with the malignant phenotype of tumor cells. The aim of this study was to investigate the...
BACKGROUND
PLAUR has been found upregulated in various tumors and closely correlated with the malignant phenotype of tumor cells. The aim of this study was to investigate the relationship between PLAUR and clear cell renal cell carcinoma (ccRCC) and its potential mechanism of promoting tumor progression.
METHODS
The expression levels and clinical significance of PLAUR, along with the associated signaling pathways, were extensively investigated in ccRCC samples obtained from The Cancer Genome Atlas (TCGA). PLAUR expression in 20 pairs of ccRCC tumor tissues and the adjacent tissues was assessed using qRT-PCR and IHC staining. Additionally, a series of experiments were conducted to investigate the impact of PLAUR suppression on cellular proliferation, migration, invasion, cell cycle progression, and apoptosis in ccRCC. The Western blot analysis was employed to investigate the expression levels of pivotal genes associated with the PI3K/AKT/mTOR signaling pathway.
RESULTS
The expression of PLAUR was significantly upregulated in ccRCC compared to normal renal tissues, and higher PLAUR expression in ccRCC was associated with a poorer prognosis than low expression. The functional investigations demonstrated that knockdown of PLAUR significantly attenuated the proliferation, migration, and invasion capabilities of ccRCC cells. Concurrently, PLAUR knockdown effectively induced cellular apoptosis, modulated the cell cycle, inhibited the EMT process, and attenuated the activation of the PI3K/AKT/mTOR signaling pathway. PLAUR may represent a key mechanism underlying ccRCC progression.
CONCLUSIONS
The involvement of PLAUR in ccRCC progression may be achieved through the activation of the PI3K/AKT/mTOR signaling pathway, making it a reliable biomarker for the identification and prediction of ccRCC.
Topics: Humans; Carcinoma, Renal Cell; TOR Serine-Threonine Kinases; Kidney Neoplasms; Signal Transduction; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Disease Progression; Cell Proliferation; Cell Line, Tumor; Male; Female; Apoptosis; Cell Movement; Middle Aged; Gene Expression Regulation, Neoplastic; Prognosis; Up-Regulation
PubMed: 38948215
DOI: 10.7717/peerj.17555 -
Oncology Research 2024This study aimed to investigate the role of receptor tyrosine kinase-like orphan receptor 2 (ROR2) in triple-negative breast cancer (TNBC).
OBJECTIVE
This study aimed to investigate the role of receptor tyrosine kinase-like orphan receptor 2 (ROR2) in triple-negative breast cancer (TNBC).
METHODS
ROR2 expression in primary TNBC and metastatic TNBC tissues was analyzed by immunohistochemical staining and PCR. ROR2 expression in TNBC cell lines was detected by PCR and Western blot analysis. The migration, invasion and chemosensitivity of TNBC cells with overexpression or knockdown of ROR2 were examined.
RESULTS
ROR2 expression was high in metastatic TNBC tissues. ROR2 knockdown suppressed the migration, invasion and chemoresistance of TNBC cells. ROR2 overexpression in MDA-MB-435 cells promoted the migration, invasion, and chemoresistance. Moreover, ROR2 knockdown in HC1599 and MDA-MB-435 adriamycin-resistant cells enhanced chemosensitivity to adriamycin. ROR2 could activate PI3K/AKT/mTOR signaling in TNBC cells.
CONCLUSION
ROR2 is upregulated and promotes metastatic phenotypes of TNBC by activating PI3K/AKT/mTOR signaling.
Topics: Humans; Triple Negative Breast Neoplasms; Receptor Tyrosine Kinase-like Orphan Receptors; TOR Serine-Threonine Kinases; Proto-Oncogene Proteins c-akt; Drug Resistance, Neoplasm; Female; Signal Transduction; Phosphatidylinositol 3-Kinases; Cell Line, Tumor; Cell Movement; Neoplasm Invasiveness; Gene Expression Regulation, Neoplastic; Doxorubicin
PubMed: 38948021
DOI: 10.32604/or.2024.045433 -
Journal of Cancer 2024Ferroptosis has been characterized as non-apoptotic programmed cell death and is considered a novel strategy for antitumor treatment. The factor that binds to inducer of...
Ferroptosis has been characterized as non-apoptotic programmed cell death and is considered a novel strategy for antitumor treatment. The factor that binds to inducer of short transcripts-1 (FBI-1) is an important proto-oncogene playing multiple roles in human malignancies and the development of resistance to therapy. However, the roles of FBI-1 in ferroptosis of endocrine independent prostate carcinoma are still unknown. The results of this study showed that FBI-1 inhibited the ferroptosis of prostate carcinoma PC-3 cells (a typical endocrine-independent prostate carcinoma cell line) via the miR-324-3p/glutathione peroxidase 4 (miR-324-3p/GPX4) axis. Overexpression of FBI-1 enhanced the expression levels of GPX4. In contrast, knockdown of FBI-1 decreased the expression of GPX4 and induced the ferroptosis of PC-3 cells. The miR-324-3p decreased the expression of GPX4 by targeting the 3'-untranslated region of GPX4 to induce ferroptosis. Notably, FBI-1 increased the expression of GPX4 by repressing the levels of miR-324-3p. The transcription of miR-324-3p was mediated by specificity protein 1 (SP1), and FBI-1 repressed the expression of miR-324-3p by repressing the activation of SP1. In clinical specimens, the endogenous levels of FBI-1 were positively associated with Glutathione Peroxidase 4 (GPX4) and negatively related with the expression of miR-324-3p. Therefore, the results indicated that the miR-324-3p/GPX4 axis participates in the FBI-1-mediated ferroptosis of prostate carcinoma cells.
PubMed: 38947389
DOI: 10.7150/jca.96306 -
Acta Dermatovenerologica Croatica : ADC Mar 2024Mutation of the BRAF oncogene is one of the most common mutations detected in human neoplasia, occurring in 40-60% of all cutaneous melanoma. BRAF is a serine/threonine...
Mutation of the BRAF oncogene is one of the most common mutations detected in human neoplasia, occurring in 40-60% of all cutaneous melanoma. BRAF is a serine/threonine protein kinase which is an essential part of the mitogen-activated protein kinase (MAPK) pathway. It is physiologically activated by RAS, but in mutated form, due to molecular conformational change, BRAF becomes constitutively active with subsequent persistent activation of downstream cytoplasmic and nuclear proteins (MEK, ERK, ETS), which finally leads to gene expression that promotes cell growth and survival. Inhibition of the altered MAPK pathway by BRAF inhibitors and combined BRAF/MEK inhibitors in BRAF mutated melanoma has become a standard therapeutic approach (1,2). We recently reported the frequency and clinicopathological features of BRAF V600E mutated melanomas in the Dalmatian region of Croatia. This report included 80 cutaneous melanomas with BRAF analyses performed at our institution until the second half of 2017, using a kit which detected only BRAF V600E mutation (3). From the second half of 2017, we started using a kit which detects several types of BRAF mutations along with NRAS mutation. The aim of this report was to determine the spectrum and frequency of different BRAF mutations in a group of skin melanomas in the Dalmatian region of Croatia and to comment on the relationship between type of BRAF mutation and therapeutic response to MAPK pathway inhibition. The analysis included 179 patients with stage 3 and stage 4 cutaneous melanoma with known BRAF/NRAS mutational status. The paraffin blocks were forwarded from four Dalmatian hospitals (Split: 139 cases, Zadar: 17 cases, Šibenik: 13 cases, Dubrovnik: 10 cases). BRAF/NRAS mutation analysis was performed at the Institute of Pathology, Clinical Hospital Center Split, Croatia, in the period from the second half of 2017 to the end of 2022. For DNA extraction analysis, hematoxylin and eosin stained slides from each submitted sample were reviewed by a pathologist, and tumor tissue was identified for analysis. For all tissue specimens, DNA was extracted from sections (10 mm thick) using the cobas® DNA Sample Preparation Kit (Roche Molecular Diagnostics), following the manufacturer's protocol. The amount of genomic DNA was quantified using the Qubit® 2.0 Fluorometer (Life Technologies) and adjusted to a fixed concentration to be added to the amplification/detection mixture. For mutation analysis, the target DNA was amplified and detected on the cobas z 480 analyzer using the amplification and detection reagents provided in the Roche BRAF/NRAS mutation test (LSR) kit, according to the manufacturer's protocol. The test results were reported as follows: BRAF exon 11 mutation detected, BRAF V600E/E2/D mutation detected, BRAF V600K mutation detected, BRAF V600R mutation detected, BRAF K601E mutation detected, NRAS (G12X, G13X, A18T, Q61X, other NRAS Ex3/4) mutation detected, mutation not detected, or invalid result (no result was obtained on the cobas test). BRAF mutation was observed in 87 patients (48.6%), NRAS mutation was found in 27 patients (15.1%), while 65 patients (36.3%) were without BRAF/NRAS mutation (Table 1). In the group of BRAF mutated melanomas, 61 cases (70.1%) had V600E/E2/D mutation, 20 cases (23%) had V600K mutation, 3 cases (3.4%) had exon 11 mutation, 2 cases (2.3%) had V600R mutation, and 1 case (1.2%) had K601E mutation (Table 2). The observed frequency of BRAF mutated melanomas in this study was similar to the frequency reported in our previous study (48.6% and 47.5%, respectively) (3). The vast majority were BRAF V600 mutations, while BRAF non-V600 mutations were rare (95.4% and 4.6%, respectively). In the group of BRAF V600 mutations, V600E/E2/D mutations predominated, followed by V600K mutations, while V600R mutations were rare. Greaves et al. reported similar frequency of BRAF V600 mutations in a group of 499 BRAF-mutated cutaneous melanomas, with V600E/E2/D mutations observed in 77.2% cases, followed by V600K mutations observed in 17.2% cases, and V600R mutations observed in 2.6% cases (4). BRAF non-V600 mutations (exon 11 and K601E mutations) were rarely observed in this study, confirming the findings of other authors (4,5). A three-class system of BRAF mutations was recently proposed that takes into account the differences in their kinase activity, with class I containing mutants with high kinase activity and high response rate to BRAF and BRAF/MEK inhibitors. Class II BRAF mutations have lower kinase activity than class I mutants, but higher than wild-type BRAF, showing resistance to BRAF inhibitor monotherapy and sensitivity to MEK and BRAF/MEK inhibitors. Finally, class III BRAF mutations are characterized by low kinase activity and low response rate to targeted therapy (6). BRAF V600 mutations belong to class I mutations, which means that the large majority of BRAF-positive melanomas in this study (95.4%) were sensitive to targeted therapy. However, the sensitivity to targeted therapy is different among different class I BRAF mutations. While large randomized controlled trials on combined BRAF/MEK inhibition showed good overall response (63-68%) and improvement of progression-free survival (PFS) and overall survival (OS) for the melanomas with most prevalent V600E and V600K mutations, Menzer et al. showed lower response rate to MAPK pathway inhibition (45%) in the group of metastatic melanomas with BRAF V600 mutations other than V600E/K. The overall response rate to MAPK pathway inhibition in the same group of melanomas with BRAF non-V600 mutations (class II and III mutations) was only 18% (7). In our group of BRAF mutated skin metastatic melanomas, we found only 6 cases (6.9%) with expected lower response rate to MAPK pathway inhibition: 2 cases with V600R mutation (class I non-V600E/K mutation), 1 case with K601E mutation (class II mutation), and 3 cases with exon 11 mutation (class II and III mutations).
Topics: Humans; Proto-Oncogene Proteins B-raf; Melanoma; Skin Neoplasms; Croatia; Mutation; Female; Male; Middle Aged; Aged; Adult; Aged, 80 and over
PubMed: 38946192
DOI: No ID Found -
Food Research International (Ottawa,... Aug 2024Cyclocarya paliurus (Batal.) leaves, which contain a range of bioactive compounds, have been used as a traditional Chinese medicine homologous food since ancient times....
Discovery and identification of natural alkaloids with potential to impact insulin resistance syndrome in Cyclocarya paliurus. (Batal) leaves by UPLC-QTOF-MS combined with HepG2 cells.
Cyclocarya paliurus (Batal.) leaves, which contain a range of bioactive compounds, have been used as a traditional Chinese medicine homologous food since ancient times. However, there is a paucity of literature on comprehensive studies of alkaloids in the leaves of Cyclocarya paliurus (Batal.). For the first time, this study aimed to discover and identify alkaloids extracted from Cyclocarya paliurus (Batal.) leaves by ultra-high performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UPLC-QTOF-MS). A total of ten alkaloids have been identified from Cyclocarya paliurus (Batal.) leaves based on accurate mass spectra (mass accuracy, isotopic spacing and distribution) and comparison to fragmentation spectra reported in the literature. In vitro, alkaloids alleviated insulin resistance by increasing glucose consumption and glycogen content in insulin resistance HepG2 cells. The RNA-seq and western blotting results showed that alkaloids could upregulate the expression of phosphatidylinositol 3-kinase (PI3K), and increase the phosphorylation of insulin receptor protein kinase B (AKT). This study not only clarified the chemical constituents and revealed that diverse alkaloids also presented from Cyclocarya paliurus (Batal.) leaves, also, it will provide chemical information on potential compounds for developing new drugs.
Topics: Plant Leaves; Alkaloids; Insulin Resistance; Hep G2 Cells; Humans; Chromatography, High Pressure Liquid; Juglandaceae; Tandem Mass Spectrometry; Plant Extracts; Proto-Oncogene Proteins c-akt
PubMed: 38945558
DOI: 10.1016/j.foodres.2024.114545 -
Translational Research : the Journal of... Jun 2024Renal aging and the subsequent rise in kidney-related diseases are attributed to senescence in renal tubular epithelial cells (RTECs). Our study revealed that the...
Renal aging and the subsequent rise in kidney-related diseases are attributed to senescence in renal tubular epithelial cells (RTECs). Our study revealed that the abnormal expression of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), a reader of RNA N6-methyladenosine, is critically involved in cisplatin-induced renal tubular senescence. In cisplatin-induced senescence of RTECs, the promoter activity and transcription of IGF2BP3 is markedly suppressed. It was due to the down regulation of MYC proto-oncogene (MYC), which regulates IGF2BP3 transcription by binding to the putative site at 1852 to 1863 of the IGF2BP3 promoter. Overexpression of IGF2BP3 ameliorated cisplatin-induced renal tubular senescence in vitro. Mechanistic studies revealed that IGF2BP3 inhibits cellular senescence in RTECs by enhancing cyclin-dependent kinase 6 (CDK6) mRNA stability and increasing its expression. The inhibition effect of IGF2BP3 on tubular senescence is partially reversed by the knockdown of CDK6. Further, IGF2BP3 recruits nuclear cap binding protein subunit 1 (NCBP1) and inhibits CDK6 mRNA decay, by recognizing mA modification. Specifically, IGF2BP3 recognizes mA motif "GGACU" at nucleotides 110-114 in the 5' untranslated region (UTR) field of CDK6 mRNA. The involvement of IGF2BP3/CDK6 in alleviating tubular senescence was confirmed in a cisplatin-induced acute kidney injury (AKI)-to-chronic kidney disease (CKD) model. Clinical data also suggests an age-related decrease in IGF2BP3 and CDK6 levels in renal tissue or serum samples from patients. These findings suggest that IGF2BP3/CDK6 may be a promising target in cisplatin-induced tubular senescence and renal failure.
PubMed: 38945255
DOI: 10.1016/j.trsl.2024.06.004 -
Fluorescence-activated nuclear sorting (FANS) of nuclei from in vitro-generated syncytiotrophoblast.Placenta Jun 2024Large, multinucleated cells, like syncytiotrophoblasts (STB), are not readily analyzed by standard methods used for single cells, such as single-cell RNA-sequencing and...
Large, multinucleated cells, like syncytiotrophoblasts (STB), are not readily analyzed by standard methods used for single cells, such as single-cell RNA-sequencing and fluorescence-activated cellular sorting (FACS). Here we have demonstrated that fluorescence-activated nuclear sorting (FANS) is suitable to analyze nuclei from STB. Human pluripotent stem cells (PSCs) can be differentiated into a mixed trophoblast populations comprising approximately 20 % STB by treatment with BMP4 (Bone Morphogenetic Protein-4), plus A83-01 and PD173074, inhibitors of activin and FGF2 signaling, respectively (the BAP model) in about a week. Here we demonstrate that FANS can be used to separate two types of STB nuclei from the nine different clusters of trophoblast nuclei previously identified in the BAP model by single nucleus RNA sequencing (snRNAseq). Rather than using cell surface markers, as in FACS, transcription factors in various combinations were employed to target specific nuclear types. Nuclei were isolated at d 8 of BAP differentiation of H1 human embryonic stem cells and fixed in 4 % paraformaldehyde. After permeabilization in 0.1 % triton X-100, nuclei were incubated for 3 and 1 h at 4 °C with primary and secondary antibodies respectively and nuclear samples were then subjected to FANS. By using markers identified by snRNA and immunohistochemistry, nuclei were first sorted into a Topoisomerase-1, or TOP1, bright population and then into the two STB subpopulations by using antibodies to JUNB (Jun B Proto-Oncogene) and TFCP2L1 (Transcription Factor CP2 Like 1). The protocol established here is simple, straightforward, and efficient and can be used on a relatively large scale to sort individual subtypes of nuclei from mixed populations of trophoblasts for further analysis.
PubMed: 38944560
DOI: 10.1016/j.placenta.2024.06.007 -
Molekuliarnaia Biologiia 2024Melatonin (N-acetyl-5-methoxytryptamine, MEL) is a hormone synthesized by the pineal gland. Due to its oncostatic effect, it can be considered as an antitumor agent and...
Melatonin (N-acetyl-5-methoxytryptamine, MEL) is a hormone synthesized by the pineal gland. Due to its oncostatic effect, it can be considered as an antitumor agent and used for combination therapy. ABT-737, a Bcl-2 inhibitor, promotes cell death after treatment with agents that induce pro-apoptotic signals. In the present study, the combined effect of MEL and ABT-737 on changes in proliferative and mitotic activity, mitochondrial membrane potential, intracellular production of reactive oxygen species (ROS), and cytosolic Ca^(2+) was studied. Moreover, changes in the expression of anti- and pro-apoptotic proteins (Bcl-2 and Bax), autophagy markers (LC3A/B (I, II)), endoplasmic reticulum stress markers (chaperones BIP and PDI, CHOP) were studied under these conditions. The effect of MEL together with ABT-737 led to an increase in the level of cytosolic Ca^(2+), intracellular production of ROS and a decrease in the membrane potential of mitochondria. The content of Bcl-2 increased, while the level of Bax decreased. Activation of CHOP stimulated autophagy and led to a decrease in the synthesis of chaperones BIP and PDI. It is assumed that melatonin can enhance the effect of other chemotherapeutic agents and can be used in the treatment of tumors.
Topics: Humans; Sulfonamides; Melatonin; Nitrophenols; Piperazines; Biphenyl Compounds; Reactive Oxygen Species; Membrane Potential, Mitochondrial; Apoptosis; Proto-Oncogene Proteins c-bcl-2; THP-1 Cells; bcl-2-Associated X Protein; Drug Synergism; Autophagy; Endoplasmic Reticulum Stress; Endoplasmic Reticulum Chaperone BiP; Cell Proliferation; Microtubule-Associated Proteins; Calcium; Neoplasm Proteins; Transcription Factor CHOP
PubMed: 38943585
DOI: No ID Found -
Molekuliarnaia Biologiia 2024Stress can play a significant role in arterial hypertension and many other complications of cardiovascular diseases. Considerable attention is paid to the study of the...
Stress can play a significant role in arterial hypertension and many other complications of cardiovascular diseases. Considerable attention is paid to the study of the molecular mechanisms involved in the body response to stressful influences, but there are still many blank spots in understanding the details. ISIAH rats model the stress-sensitive form of arterial hypertension. ISIAH rats are characterized by genetically determined enhanced activities of the hypothalamic-pituitary-adrenocortical and sympathetic-adrenomedullary systems, suggesting a functional state of increased stress reactivity. For the first time, the temporal expression patterns of Fos and several related genes were studied in the hypothalamus of adult male hypertensive ISIAH rats after a single exposure to restraint stress for 30, 60, or 120 min. Fos transcription was activated and peaked 1 h after the start of restraint stress. The time course of Fos activation coincided with that of blood pressure increase after stress. Activation of hypothalamic neurons also alters the transcription levels of several transcription factor genes (Jun, Nr4a3, Jdp2, and Ppargc1a), which are associated with the development of cardiovascular diseases. Because Fos induction is a marker of brain neuron activation, activation of hypothalamic neurons and an increase in blood pressure were concluded to accompany increased stress reactivity of the hypothalamic-pituitary-adrenocortical and sympathoadrenal systems in hypertensive ISIAH rats during short-term restraint.
Topics: Animals; Hypertension; Rats; Hypothalamus; Male; Gene Expression Regulation; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Proto-Oncogene Proteins c-fos; Restraint, Physical; Stress, Psychological; Blood Pressure; Stress, Physiological; Neurons
PubMed: 38943581
DOI: No ID Found