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101.
In order to examine the effects of estrogen, androgen, and phytoestrogen on maternal behavior induced by exposure to fresh pups in ovariectomized nulliparous rats, 1 mg estradiol benzoate (EB), 1 mg testosterone propionate (TP), 1 mg coumestrol (CM), or oil (female control) was injected subcutaneously daily for 10 days. To elucidate the sex difference, 1 mg EB or oil (male control) was injected in orchidectomized rats by the same method as that used in nulliparous rats. Exposure to fresh pups was started 6 days after the first injection. Behavioral tests were carried out daily for 5 days from the first exposure to the last on the 10th day. In the behavioral test, the onset of retrieving and licking behaviors was recorded. In female control rats, the median onset day of retrieving behavior was day 5. Onset in the EB female group was day 1.5, which was shorter than that in the female control (P<0.05). TP female and CM female rats started to show retrieving at day 5 and day 4.5, respectively, comparable to the female controls. In males, the median day of retrieving onset in the control and EB groups was over day 5 and day 4.5, respectively. No statistical difference was seen between the female and male controls. In contrast, there was a difference between the EB-treated female and EB male groups. Licking activity was less frequent than seen in the retrieving behavior among all groups, but there was no statistical difference among the groups. These results suggest that estrogen facilitates retrieving behavior in female, but not in male rats. TP and CM have no effect on retrieving behavior in female rats. 相似文献
102.
Keitaro Yamanouchi Erica Yada Naomi Ishiguro Masugi Nishihara 《Cellular physiology and biochemistry》2007,20(6):781-790
The importance of connexins is implicated in proliferation and differentiation of cells. In skeletal muscle cells, connexin43 (Cx43) has been identified as the major connexin, and gap-junctional communication mediated by connexins has been shown to be required for their myogenic differentiation. In addition, inhibition of connexin function has been shown to induce transdifferentiation of osteoblasts to an adipocytic phenotype. In the present study, we examined whether the inhibition of connexin function could induce phenotypic changes in skeletal muscle cells. Treatment of skeletal muscle cells with an inhibitor of connexin function, 18alpha-glycyrrhetinic acid (AGRA), resulted in a reduction in the number of MyoD-positive cells and complete inhibition of myotube formation, concomitantly with an increase in the number of C/EBPalpha-positive cells. AGRA-treated cells cultured in adipogenic differentiation medium could give rise to mature adipocytes that express both PPARgamma and C/EBPalpha. The presence of AGRA during adipogenic differentiation did not inhibit adipogenesis of skeletal muscle cells. AGRA treatment did not affect Cx43 expression in skeletal muscle cells but reduced its phosphorylation. These results indicate that inhibition of connexin function induces phenotypic changes of skeletal muscle cells to enter adipogenesis. 相似文献
103.
Mapping and characterization of seed dormancy QTLs using chromosome segment substitution lines in rice 总被引:1,自引:0,他引:1
Marzougui S Sugimoto K Yamanouchi U Shimono M Hoshino T Hori K Kobayashi M Ishiyama K Yano M 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2012,124(5):893-902
Seed dormancy—the temporary failure of a viable seed to germinate under favorable conditions—is a complex characteristic influenced
by many genes and environmental factors. To detect the genetic factors associated with seed dormancy in rice, we conducted
a QTL analysis using chromosome segment substitution lines (CSSLs) derived from a cross between Nona Bokra (strong dormancy)
and Koshihikari (weak dormancy). Comparison of the levels of seed dormancy of the CSSLs and their recurrent parent Koshihikari
revealed that two chromosomal regions—on the short arms of chromosomes 1 and 6—were involved in the variation in seed dormancy.
Further genetic analyses using an F2 population derived from crosses between the CSSLs and Koshihikari confirmed the allelic differences and the chromosomal locations
of three putative QTLs: Sdr6 on chromosome 1 and Sdr9 and Sdr10 on chromosome 6. The Nona Bokra alleles of the three QTLs were associated with decreased germination rate. We discuss the
physiological features of the CSSLs and speculate on the possible mechanisms of dormancy in light of the newly detected QTLs. 相似文献
104.
Macrophage migration inhibitory factor induces B cell survival by activation of a CD74-CD44 receptor complex 总被引:1,自引:0,他引:1
Gore Y Starlets D Maharshak N Becker-Herman S Kaneyuki U Leng L Bucala R Shachar I 《The Journal of biological chemistry》2008,283(5):2784-2792
Macrophage migration inhibitory factor (MIF) is an upstream activator of innate immunity that regulates subsequent adaptive responses. It was previously shown that in macrophages, MIF binds to a complex of CD74 and CD44, resulting in initiation of a signaling pathway. In the current study, we investigated the role of MIF in B cell survival. We show that in B lymphocytes, MIF initiates a signaling cascade that involves Syk and Akt, leading to NF-kappaB activation, proliferation, and survival in a CD74- and CD44-dependent manner. Thus, MIF regulates the adaptive immune response by maintaining the mature B cell population. 相似文献
105.
Yokoyama U Minamisawa S Quan H Akaike T Jin M Otsu K Ulucan C Wang X Baljinnyam E Takaoka M Sata M Ishikawa Y 《American journal of physiology. Heart and circulatory physiology》2008,295(4):H1547-H1555
Vascular remodeling after mechanoinjury largely depends on the migration of smooth muscle cells, an initial key step to wound healing. However, the role of the second messenger system, in particular, the cAMP signal, in regulating such remodeling remains controversial. Exchange protein activated by cAMP (Epac) has been identified as a new target molecule of the cAMP signal, which is independent from PKA. We thus examined whether Epac plays a distinct role from PKA in vascular remodeling. To examine the role of Epac and PKA in migration, we used primary culture smooth muscle cells from both the fetal and adult rat aorta. A cAMP analog selective to PKA, 8-(4-parachlorophenylthio)-cAMP (pCPT-cAMP), decreased cell migration, whereas an Epac-selective analog, 8-pCPT-2'-O-Me-cAMP, enhanced migration. Adenovirus-mediated gene transfer of PKA decreased cell migration, whereas that of Epac1 significantly enhanced cell migration. Striking morphological differences were observed between pCPT-cAMP- and 8-pCPT-2'-O-Me-cAMP-treated aortic smooth muscle cells. Furthermore, overexpression of Epac1 enhanced the development of neointimal formation in fetal rat aortic tissues in organ culture. When the mouse femoral artery was injured mechanically in vivo, we found that the expression of Epac1 was upregulated in vascular smooth muscle cells, whereas that of PKA was downregulated with the progress of neointimal thickening. Our findings suggest that Epac1, in opposition to PKA, increases vascular smooth muscle cell migration. Epac may thus play an important role in advancing vascular remodeling and restenosis upon vascular injury. 相似文献
106.
107.
The limitations of studies of clarification of response elements of whey acidic protein (WAP) gene to hormones using mammary cell lines has been shown. We studied the response of the upstream region (2.6 kb) of WAP to various steroid hormones using gonadectomized mWAP/hGH transgenic mice. Ovariectomy or castration for transgenic mice was performed at 10 days or 30 days post partum. Various steroid hormones were administered daily for 10 days to the gonadectomized transgenic mice after they reached 2 months of age. Prior to the hormonal administration and 24 hr after the final administration, blood was collected and the hGH levels in the plasma was measured by RIA. Daily doses of estradiol-17 beta were significantly more effective at increasing hGH levels in transgenic females ovariectomized at 10 days post partum than progesterone of an equal dose. A combined dose of progesterone and of estradiol-17 beta significantly amplified the increase of hGH levels accompanied by the great development of mammary glands, compared to a dose of progesterone alone. Corticosterone induced only a slight increase of hGH, while testosterone had no effect. The doses of gonadal steroid hormones did not induce an increase in hGH levels and development of mammary glands in the castrated transgenic males. The results showed that the response of 5' region of WAP requires at least some extended development of the mammary gland and that the 2.6 kb upstream region of the exogenous WAP gene contained the element responsive to ovarian hormones. 相似文献
108.
Jun Yamanouchi Atsushi Takatori Etsuko Nishida Seiji Kawamura Yasuhiro Yoshikawa 《Experimental Animals》2002,51(1):33-41
Syrian hamsters of the APA strain (APA hamsters) have recently been demonstrated to develop atheromatous lesions in the aortic arches under the diabetic condition induced by a single injection of streptozotocin (SZ). Various lipoprotein receptors are reported to play important roles in atherogenesis mainly in vitro, while there are few reports on the relative expressions of these receptors in vivo. In this study, we therefore examined messenger RNA (mRNA) expressions of several lipoprotein receptors on the aortic arches of diabetic APA hamsters at 6, 14 and 26 weeks after the injection (WAI) of SZ. In semi-quantitative RT-PCR, scavenger receptor (SR)-AI, macrosialin (MS)/CD68, and receptor for advanced glycation end-products (RAGE) mRNAs showed significant increases at 6 WAI of SZ, and SR-AI and CD36 mRNA obviously increased until 26 WAI, as compared with the control. Low-density lipoprotein receptor mRNA showed a significant decrease at 14 and 26 WAI, and SR-BI mRNA significantly decreased at 6 and 14 WAI, as compared with the control. Very low-density lipoprotein receptor mRNA was at the same level as the control. By means of in situ hybridization, SR-AI, MS/CD68 and RAGE mRNA were detected in the foam cells of the fatty streaks at 6 WAI, which suggested that SR-AI, MS/CD68 and RAGE play crucial roles in the formation of the fatty streaks, the initial lesions of atherogenesis in diabetic APA hamsters. SR-AI and CD36 were also believed to be related to the progression of atherogenesis in this model. 相似文献
109.
Toru Akaike Mei-Hua Jin Utako Yokoyama Hiroko Izumi-Nakaseko Qibin Jiao Shiho Iwasaki Mari Iwamoto Shigeru Nishimaki Motohiko Sato Shumpei Yokota Yoshinori Kamiya Satomi Adachi-Akahane Yoshihiro Ishikawa Susumu Minamisawa 《The Journal of biological chemistry》2009,284(36):24025-24034
The ductus arteriosus (DA), an essential vascular shunt for fetal circulation, begins to close immediately after birth. Although Ca2+ influx through several membrane Ca2+ channels is known to regulate vasoconstriction of the DA, the role of the T-type voltage-dependent Ca2+ channel (VDCC) in DA closure remains unclear. Here we found that the expression of α1G, a T-type isoform that is known to exhibit a tissue-restricted expression pattern in the rat neonatal DA, was significantly up-regulated in oxygenated rat DA tissues and smooth muscle cells (SMCs). Immunohistological analysis revealed that α1G was localized predominantly in the central core of neonatal DA at birth. DA SMC migration was significantly increased by α1G overexpression. Moreover, it was decreased by adding α1G-specific small interfering RNAs or using R(−)-efonidipine, a highly selective T-type VDCC blocker. Furthermore, an oxygenation-mediated increase in an intracellular Ca2+ concentration of DA SMCs was significantly decreased by adding α1G-specific siRNAs or using R(−)-efonidipine. Although a prostaglandin E receptor EP4 agonist potently promoted intimal thickening of the DA explants, R(−)-efonidipine (10−6 m) significantly inhibited EP4-promoted intimal thickening by 40% using DA tissues at preterm in organ culture. Moreover, R(−)-efonidipine (10−6 m) significantly attenuated oxygenation-induced vasoconstriction by ∼27% using a vascular ring of fetal DA at term. Finally, R(−)-efonidipine significantly delayed the closure of in vivo DA in neonatal rats. These results indicate that T-type VDCC, especially α1G, which is predominantly expressed in neonatal DA, plays a unique role in DA closure, implying that T-type VDCC is an alternative therapeutic target to regulate the patency of DA.The ductus arteriosus (DA)2 is an essential vascular shunt between the aortic arch and the pulmonary trunk during a fetal period (1). After birth, the DA closes immediately in accordance with its smooth muscle contraction and vascular remodeling, whereas the connecting vessels such as the aorta and pulmonary arteries remain open. When the DA fails to close after birth, the condition is known as patent DA, which is a common form of congenital heart defect. Patent DA is also a frequent problem with significant morbidity and mortality in premature infants. Investigating the molecular mechanism of DA closure is important not only for vascular biology but also for clinical problems in pediatrics.Voltage-dependent Ca2+ channels (VDCCs) consist of multiple subtypes, named L-, N-, P/Q-, R-, and T-type. L-type VDCCs are known to play a primary role in regulating Ca2+ influx and thus vascular tone in the development of arterial smooth muscle including the DA (2–4). Our previous study demonstrated that all T-type VDCCs were expressed in the rat DA (5). α1G subunit, especially, was the most dominant isoform among T-type VDCCs. The abundant expression of α1G subunit suggests that it plays a role in the vasoconstriction and vascular remodeling of the DA. In this regard, Nakanishi et al. (6) demonstrated that 0.5 mm nickel, which blocks T-type VDCC, inhibited oxygen-induced vasoconstriction of the rabbit DA. On the other hand, Tristani-Firouzi et al. (7) demonstrated that T-type VDCCs exhibited little effect on oxygen-sensitive vasoconstriction of the rabbit DA. Thus, the role of T-type VDCCs in DA vasoconstriction has remained controversial.In addition to their role in determining the contractile state, a growing body of evidence has demonstrated that T-type VDCCs play an important role in regulating differentiation (8, 9), proliferation (10–12), migration (13, 14), and gene expression (15) in vascular smooth muscle cells (SMCs). Hollenbeck et al. (16) and Patel et al. (17) demonstrated that nickel inhibited platelet-derived growth factor-BB-induced SMC migration. Rodman et al. (18) demonstrated that α1G promoted SMC proliferation in the pulmonary artery. The DA dramatically changes its morphology during development. Intimal cushion formation, a characteristic feature of vascular remodeling of the DA (19–21), involves many cellular processes: an increase in SMC migration and proliferation, production of hyaluronic acid under the endothelial layer, impaired elastin fiber assembly, and so on (1, 19, 21–23). Although our previous study demonstrated that T-type VDCCs are involved in smooth muscle cell proliferation in the DA (5), the role of T-type VDCCs in vascular remodeling of the DA has remained poorly understood.In the present study, we hypothesized that T-type VDCCs, especially α1G subunit, associate with vascular remodeling and vasoconstriction in the DA. To test our hypothesis, we took full advantage of recent molecular and pharmacological developments. We chose the recently developed, highly selective T-type VDCC blocker R(−)-efonidipine instead of low dose nickel for our study. Selective inhibition or activation of α1G subunit was also obtained using small interfering RNA (siRNA) technology or by overexpression of the α1G subunit gene, respectively. We found that Ca2+ influx through T-type VDCCs promoted oxygenation-induced DA closure through SMC migration and vasoconstriction. 相似文献
110.