• Title/Summary/Keyword: TRPV

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Klotho : Expression and Regulation at the Maternal-Conceptus Interface in Pigs

  • Choi, Yohan;Seo, Heewon;Shim, Jangsoo;Hyun, Sang-Hwan;Lee, Eunsong;Ka, Hakhyun
    • Journal of Embryo Transfer
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    • v.29 no.4
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    • pp.375-383
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    • 2014
  • Klotho (KL) is a single transmembrane protein composed of KL1 and KL2 repeats possessing ${\beta}$-glucuronidase activity and maintains calcium homeostasis in physiological state. It has been implicated in pigs that calcium is important for the establishment and maintenance of pregnancy, and our previous study has shown that transient receptor potential vanilloid type 6 (TRPV6), a calcium ion transporter, is predominantly expressed in the uterine endometrium during pregnancy in pigs. However, expression and function of KL in the uterine endometrium has not been determined in pigs. Thus, the present study determined expression and regulation of KL in the uterine endometrium during the estrous cycle and pregnancy in pigs. Real-time RT-PCR analysis showed that levels of KL mRNA decreased between Days 12 to 15 of the estrous cycle, and its expression showed a biphasic manner during pregnancy. KL mRNA was expressed in conceptuses and in chorioallantoic tissues during pregnancy. Explant culture study showed that expression levels of KL were not affected by treatment of steroid hormones or interleukin-1beta during the implantation period. Furthermore, levels of KL mRNA in the uterine endometrium from gilts carrying somatic cell nuclear transfer (SCNT)-derived embryos were significantly lower than those from gilts carrying natural mating-derived embryos on Day 12 of pregnancy. These results exhibited that KL was expressed at the maternal-conceptus interface in a pregnancy status- and stage-specific manner, and its expression was affected by SCNT procedure, suggesting that KL may play an important role in the establishment and maintenance of pregnancy in pigs.

Atypical triggers in trigeminal neuralgia: the role of A-delta sensory afferents in food and weather triggers

  • Koh, Wenjun;Lim, Huili;Chen, Xuanxuan
    • The Korean Journal of Pain
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    • v.34 no.1
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    • pp.66-71
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    • 2021
  • Background: Trigeminal neuralgia is a debilitating craniofacial pain syndrome that is characterized by paroxysms of intense, short-lived electric shock-like pains in the trigeminal nerve distribution. Recently, the presence of triggers has become one of the key diagnostic criteria in the 3rd edition of the International Classification of Headache Disorders. Light touch is the most common trigger, however other non-mechanical triggers, such as cold weather and certain foods, have been thought to provoke trigeminal neuralgia anecdotally. We aimed to characterize the prevalence and characteristics of these atypical triggers. Methods: We conducted a retrospective, cross-sectional study of atypical triggers in trigeminal neuralgia patients seen in a tertiary pain clinic in Singapore. Patients were recruited via clinic records, and study data were identified from physician documentation. Results: A total of 60 patients met the inclusion criteria. Weather triggers were observed in 12 patients (20%), of which five patients (8%) reported strong winds, 4 patients (7%) reported cold temperatures, and 3 patients (5%) reported cold winds as triggers. Fifteen patients (25%) had a specific food trigger, of which 10 patients (17%) reported hard or tough food, 5 patients (8%) reported hot/cold food, 4 patients (7%) reported spicy food, and 2 patients (3%) reported sweet food as triggers. Conclusions: Although trigeminal neuralgia is most commonly triggered by mechanical stimuli, atypical triggers such as cold temperatures and certain foods are seen in a significant proportion of patients. These atypical triggers may share a common pathway of sensory afferent Aδ fiber activation.

INHIBITORY EFFECT OF OCTYL-PHENOL AND BISPHENOL A ON CALCIUM SIGNALING IN CARDIOMYOCYTE DIFFERENTIATION OF MOUSE EMBRYONIC STEM CELLS

  • J.-H. LEE;Y.-M. YOO;E.-M. JUNG;CH. AHN;E.-B. JEUNG
    • The Korean Journal of Physiology and Pharmacology
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    • v.70 no.3
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    • pp.435-442
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    • 2019
  • Endocrine-disrupting chemicals (EDCs) have structures similar to steroid hormones and can interfere with hormone synthesis and normal physiological functions of reproductive organs. For example, sex steroid hormones influence calcium signaling of the cardiac muscle in early embryo development. To confirm the effect of progesterone (P4), octyl-phenol (OP), and bisphenolA(BPA) on early differentiation of mouse embryonic stem cells(mESCs) into cardiomyocytes, mESCs were treated with P4, OP, and BPA two days after attachment and media were replaced every two days. In addition, cells were treated with mifepristone (RU486), a synthetic steroid that has an affinity for progesterone receptor (Pgr), for one day starting on day 11. Beating ratio was decreased with P4, OP, and BPA treatment. The Pgr mRNA level was significantly increased in the P4-, OP- and BPA-treated groups. However, the mRNA level of the calcium channel gene (Trpv2), contraction-related genes (Ryr2, Cam2, and Mylk3) and cardiac development and morphogenesis genes (Rbp4, Ly6e, and Gata4) were significantly decreased in the P4-, OP-, and BPA-treated groups. Interestingly, treatment with RU486 rescued the altered calcium channel gene, contraction-related genes, and cardiac development and morphogenesis genes. P4, OP, and BPA treatments reduced the intracellular calcium level. Taken together, these results indicate that EDCs (OP and BPA) has a structure similar to that of endogenous steroid hormones such as progesterone and estrogen, and OP and BPA act like progesterone to inhibit and disrupt cardiomyocyte differentiation of mESCs.

R-type Calcium Channel Isoform in Rat Dorsal Root Ganglion Neurons

  • Fang, Zhi;Hwang, Jae-Hong;Kim, Joong-Soo;Jung, Sung-Jun;Oh, Seog-Bae
    • The Korean Journal of Physiology and Pharmacology
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    • v.14 no.1
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    • pp.45-49
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    • 2010
  • R-type $Ca_v2.3$ high voltage-activated $Ca^{2+}$ channels in peripheral sensory neurons contribute to pain transmission. Recently we have demonstrated that, among the six $Ca_v2.3$ isoforms ($Ca_v2.3a{\sim}Ca_v2.3e$), the $Ca_v2.3e$ isoform is primarily expressed in trigeminal ganglion (TG) nociceptive neurons. In the present study, we further investigated expression patterns of $Ca_v2.3$ isoforms in the dorsal root ganglion (DRG) neurons. As in TG neurons, whole tissue RT-PCR analyses revealed the presence of two isoforms, $Ca_v2.3a$ and $Ca_v2.3e$, in DRG neurons. Single-cell RT-PCR detected the expression of $Ca_v2.3e$ mRNA in 20% (n=14/70) of DRG neurons, relative to $Ca_v2.3a$ expression in 2.8% (n=2/70) of DRG neurons. $Ca_v2.3e$ mRNA was mainly detected in small-sized neurons (n=12/14), but in only a few medium-sized neurons (n=2/14) and not in large-sized neurons, indicating the prominence of $Ca_v2.3e$ in nociceptive DRG neurons. Moreover, $Ca_v2.3e$ was preferentially expressed in tyrosine-kinase A (trkA)-positive, isolectin B4 (IB4)-negative and transient receptor potential vanilloid 1 (TRPV1)-positive neurons. These results suggest that $Ca_v2.3e$ may be the main R-type $Ca^{2+}$ channel isoform in nociceptive DRG neurons and thereby a potential target for pain treatment, not only in the trigeminal system but also in the spinal system.

Structural Study of the Cytosolic C-terminus of Vanilloid Receptor 1

  • Seo, Min-Duk;Won, Hyung-Sik;Oh, Uh-Taek;Lee, Bong-Jin
    • Journal of the Korean Magnetic Resonance Society
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    • v.11 no.2
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    • pp.85-94
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    • 2007
  • Vanilloid receptor I [transient receptor potential vanilloid subfamily member 1 (TRPV1), also known as VR1] is a non-selective cationic channel activated by noxious heat, vanilloids, and acid, thereby causing pain. VR1 possesses six transmembrane domain and N-and C-terminus cytosolic domains, and appears to be a homotetramer. We studied the structural properties of Cterminus of VR1 (VR1C) using CD and NMR spectroscopy. DPC micelles, with a zwitterionic surface, and SDS micelles, with a negatively charged surface, were used as a membrane mimetic model system. Both SDS and DPC micelles could increase the stability of helical structures and/or reduce the aggregation form of the VR1C. However, the structural changing mode of the VR1C induced by the SDS and DPC micelles was different. The changes according to the various pHs were also different in two micelles conditions. Because the net charges of the SDS and DPC micelles are negative and neutral, respectively, we anticipate that this difference might affect the structure of the VR1C by electrostatic interaction between the surface of the VR1C and phospholipids of the detergent micelles. Based on these similarity and dissimilarity of changing aspects of the VR1C, it is supposed that the VR1C probably has the real pI value near the pH 7. Generally, mild extracellular acidic pH ($6.5{\sim}6.8$) potentiates VRI channel activation by noxious heat and vanilloids, whereas acidic conditions directly activate the channel. The channel activation of the VRI might be related to the structural change of VR1C caused by pH (electrostatic interactions), especially near the pH 7. By measuring the $^1-^{15}N$ TROSY spectra of the VR1C, we could get more resolved and dispersed spectra at the low pH and/or detergent micelles conditions. We will try to do further NMR experiments in low pH with micelles conditions in order to get more information about the structure of VR1C.

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Inhibitory Effects of Ssanghwa-tang on Lung Injury and Muscle Loss in a Cigarette Smoke Extract and Lipopolysaccharide-induced Chronic Obstructive Pulmonary Disease Mouse Model (표준담배추출물과 Lipopolysaccharide로 유발한 만성폐쇄성폐질환 동물모델에서 쌍화탕의 폐손상 및 근감소 억제 효과)

  • Jin-kwan Choi;Won-kyung Yang;Su-won Lee;Seong-cheon Woo;Seung-hyung Kim;Yang-chun Park
    • The Journal of Internal Korean Medicine
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    • v.45 no.1
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    • pp.11-30
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    • 2024
  • Objectives: This study evaluated the effects of Ssanghwa-tang (SHT) on lung injury and muscle loss in a COPD mouse model. Methods: C57BL/6 mice were challenged with cigarette smoke extract and lipopolysaccharide, and then treated with two concentrations of SHT (250 and 500 mg/kg). After sacrifice, the bronchoalveolar lavage fluid (BALF) or lung tissue was analyzed by cytospin, ELISA, real-time PCR, flow cytometry analysis, and H&E and Masson's trichrome staining. The grip strength of COPD mice was measured using a grip strength meter. The running time of COPD mice was measured by a treadmill test. Muscle tissue of the quadriceps was stained with H&E and Masson's trichrome staining. Results: SHT significantly inhibited the increase in neutrophil numbers in BALF and significantly decreased immune cell activity in BALF and lung tissue. It also significantly inhibited the increase in TNF-α, IL-17, and MIP2 in BALF. Real-time PCR analysis revealed that the mRNA expression of TNF-α, IL-17, MIP2, and TRPV1 in lung tissue showed a significant decrease compared with the control group. Lung tissue damage was significantly reduced in the histological analysis. The grip strength and running time of the COPD mice showed a significant decrease compared with the control group. In histological staining, SHT was found to reduce the damage to muscle tissue. Conclusions: This study indicates that SHT can be used as a therapeutic agent for COPD patients by inhibiting lung injury and muscle loss.