• 제목/요약/키워드: Rho kinase

검색결과 111건 처리시간 0.023초

Expression patterns of Rho-associated protein kinase signaling pathway-related genes in mouse submandibular glands

  • Kim, Ki-Chul;Roh, Sangho
    • International Journal of Oral Biology
    • /
    • 제46권2호
    • /
    • pp.81-84
    • /
    • 2021
  • Salivary glands are exocrine glands that secrete saliva into the oral cavity, and secreted saliva plays essential roles in oral health. Therefore, maintaining the salivary glands in an intact state is required for proper production and secretion of saliva. To investigate a specific signaling pathway that might affect the maintenance of mouse submandibular gland (SMGs), RNA sequencing was performed. In SMGs, downregulated expression patterns of Rho-associated protein kinase (ROCK) signaling pathway-related genes, including Rhoa, Rhob, Rhoc, Rock1, and Rock2, were observed. Gene expression profiling analyses of these genes indicate that the ROCK signaling pathway is a potential signal for SMG maintenance.

The Inhibitory Mechanism of Gentamicin on Electrical Field Stimulation Response in Rat Bladder Smooth Muscle

  • Min, Chang Ho;Wang, YiYi;Bae, Jinhyung;Han, Jung Hoon;Sohn, Uy Dong
    • The Korean Journal of Physiology and Pharmacology
    • /
    • 제19권5호
    • /
    • pp.473-478
    • /
    • 2015
  • To see the inhibitory mechanism of gentamicin in response to electrical field stimulation (EFS) using the rat bladder smooth muscle, atropine or guanethidine was treated but had no effect. Methylsergide, a non-selective 5-$HT_1$, 5-$HT_2$ receptor antagonist was also treated but had on effect. Kinase inhibitors, such as chelerythrine (PKC inhibitor), ML-9 (MLCK inhibitor), or Y27632 (rho kinase inhibitor) were pretreated before gentamicin treatment, but did not have effect. For U73122, a phospholipase C (PLC) inhibitor however, the inhibitory effect to gentamicin was significantly attenuated in all frequencies given by the EFS. Therefore gentamicin induced inhibitory effect on EFS response in rat bladder smooth muscle was not mediated by the activation of adrenergic, cholinergic, or serotonergic receptor. The inhibition of gentamicin might be mediated through the PLC dependent pathway, but not through the PKC, MLCK or rho kinase dependent pathway.

Depletion of Janus kinase-2 promotes neuronal differentiation of mouse embryonic stem cells

  • Oh, Mihee;Kim, Sun Young;Byun, Jeong-Su;Lee, Seonha;Kim, Won-Kon;Oh, Kyoung-Jin;Lee, Eun-Woo;Bae, Kwang-Hee;Lee, Sang Chul;Han, Baek-Soo
    • BMB Reports
    • /
    • 제54권12호
    • /
    • pp.626-631
    • /
    • 2021
  • Janus kinase 2 (JAK2), a non-receptor tyrosine kinase, is a critical component of cytokine and growth factor signaling pathways regulating hematopoietic cell proliferation. JAK2 mutations are associated with multiple myeloproliferative neoplasms. Although physiological and pathological functions of JAK2 in hematopoietic tissues are well-known, such functions of JAK2 in the nervous system are not well studied yet. The present study demonstrated that JAK2 could negatively regulate neuronal differentiation of mouse embryonic stem cells (ESCs). Depletion of JAK2 stimulated neuronal differentiation of mouse ESCs and activated glycogen synthase kinase 3β, Fyn, and cyclin-dependent kinase 5. Knockdown of JAK2 resulted in accumulation of GTP-bound Rac1, a Rho GTPase implicated in the regulation of cytoskeletal dynamics. These findings suggest that JAK2 might negatively regulate neuronal differentiation by suppressing the GSK-3β/Fyn/CDK5 signaling pathway responsible for morphological maturation.

Nicotine in High Concentration Causes Contraction of Isolated Strips of Rabbit Corpus Cavernosum

  • Nguyen, Hoai Bac;Lee, Shin Young;Park, Soo Hyun;Han, Jun Hyun;Lee, Moo Yeol;Myung, Soon Chul
    • The Korean Journal of Physiology and Pharmacology
    • /
    • 제19권3호
    • /
    • pp.257-262
    • /
    • 2015
  • It is well known that cigarette smoke can cause erectile dysfunction by affecting the penile vascular system. However, the exact effects of nicotine on the corpus cavernosum remains poorly understood. Nicotine has been reported to cause relaxation of the corpus cavernosum; it has also been reported to cause both contraction and relaxation. Therefore, high concentrations of nicotine were studied in strips from the rabbit corpus cavernosum to better understand its effects. The proximal penile corpus cavernosal strips from male rabbits weighing approximately 4 kg were used in organ bath studies. Nicotine in high concentrations ($10^{-5}{\sim}10^{-4}M$) produced dose-dependent contractions of the corpus cavernosal strips. The incubation with $10^{-5}M$ hexamethonium (nicotinic receptor antagonist) significantly inhibited the magnitude of the nicotine associated contractions. The nicotine-induced contractions were not only significantly inhibited by pretreatment with $10^{-5}M$ indomethacin (nonspecific cyclooxygenase inhibitor) and with $10^{-6}M$ NS-398 (selective cyclooxygenase inhibitor), but also with $10^{-6}M$ Y-27632 (Rho kinase inhibitor). Ozagrel (thromboxane $A_2$ synthase inhibitor) and SQ-29548 (highly selective TP receptor antagonist) pretreatments significantly reduced the nicotine-induced contractile amplitude of the strips. High concentrations of nicotine caused contraction of isolated rabbit corpus cavernosal strips. This contraction appeared to be mediated by activation of nicotinic receptors. Rho-kinase and cyclooxygenase pathways, especially cyclooxygenase-2 and thromboxane $A_2$, might play a pivotal role in the mechanism associated with nicotine-induced contraction of the rabbit corpus cavernosum.

Efficient primary culture model of patient-derived tumor cells from colorectal cancer using a Rho-associated protein kinase inhibitor and feeder cells

  • HYE KYUNG HONG;DAE HEE PYO;TAE WON KIM;NAK HYEON YUN;YEO SONG LEE;SU JEONG SONG;WOO YONG LEE;YONG BEOM CHO
    • Oncology Letters
    • /
    • 제42권5호
    • /
    • pp.2029-20238
    • /
    • 2019
  • In vitro culture of patient-derived tumor cells offers many advantages in the development of novel therapies for colorectal cancer. Although various culture systems have been developed, the long-term expansion of patient-derived tumor cells remains challenging. The present results suggested that tumor cells isolated from colorectal cancer patient-derived xenografts can be efficiently immortalized in conditioned medium from irradiated feeder cells containing Y-27632, a rho-associated coiled-coil containing protein kinase (ROCK) inhibitor. Patient-derived tumor cells proliferated rapidly, reaching 90-95% confluence in ~6 days. Short tandem repeat analysis suggested that these tumor tissues and cultured cells presented 13 identical short tandem repeat loci, including Amelogenin, Penta E, Penta D, D2S1338 and D19S433. Their epithelial phenotype was confirmed by staining for epithelial cell adhesion molecule and cytokeratin 20, whereas vimentin was used as a mesenchymal marker. When cells were transferred to 3D cultures, they continued to proliferate, forming well-defined tumor spheroids. Expression levels of human telomerase reverse transcriptase and C-Myc mRNA were increased in cultured cells. Finally, immortalized cells were used for the screening of 65 anticancer drugs approved by the Food and Drug Administration, allowing the identification of gene-drug associations. In the present study, primary culture models of colorectal cancer were efficiently established using a ROCK inhibitor and feeder cells, and this approach could be used for personalized treatment strategies for patients with colorectal cancer.

Therapeutic potential of targeting kinase inhibition in patients with idiopathic pulmonary fibrosis

  • Kim, Suji;Lim, Jae Hyang;Woo, Chang-Hoon
    • Journal of Yeungnam Medical Science
    • /
    • 제37권4호
    • /
    • pp.269-276
    • /
    • 2020
  • Fibrosis is characterized by excessive accumulation of extracellular matrix components. The fibrotic process ultimately leads to organ dysfunction and failure in chronic inflammatory and metabolic diseases such as pulmonary fibrosis, advanced kidney disease, and liver cirrhosis. Idiopathic pulmonary fibrosis (IPF) is a common form of progressive and chronic interstitial lung disease of unknown etiology. Pathophysiologically, the parenchyma of the lung alveoli, interstitium, and capillary endothelium becomes scarred and stiff, which makes breathing difficult because the lungs have to work harder to transfer oxygen and carbon dioxide between the alveolar space and bloodstream. The transforming growth factor beta (TGF-β) signaling pathway plays an important role in the pathogenesis of pulmonary fibrosis and scarring of the lung tissue. Recent clinical trials focused on the development of pharmacological agents that either directly or indirectly target kinases for the treatment of IPF. Therefore, to develop therapeutic targets for pulmonary fibrosis, it is essential to understand the key factors involved in the pathogenesis of pulmonary fibrosis and the underlying signaling pathway. The objective of this review is to discuss the role of kinase signaling cascades in the regulation of either TGF-β-dependent or other signaling pathways, including Rho-associated coiled-coil kinase, c-jun N-terminal kinase, extracellular signal-regulated kinase 5, and p90 ribosomal S6 kinase pathways, and potential therapeutic targets in IPF.

플로레틴(Phloretin)의 혈관내피수축 융합효과와 관련기전 연구 (The Convergence Effect of Phloretin Existent in Plants on Vascular Contractility)

  • 방준석;제현동;민영실
    • 융합정보논문지
    • /
    • 제10권10호
    • /
    • pp.143-149
    • /
    • 2020
  • 이 실험에서 뇌졸중, 심혈관계 질환 등에 대해 치료 활성이 기대되는 플로레틴(phloretin) - 사과나무 잎과 개살구의 주성분 - 에서의 쥐의 대동맥에서 ROCK(Rho연관 인산화효소) 불활성화를 통해 혈관수축을 억제한다는 기전을 확인하고자 한다. 개체에서 분리되고 내피가 유지되거나 손상된 동맥의 고리 조각은 2개의 금속 고리로 근운동기록기(myograph) 수조 안에 현수되었고 아래쪽 고리는 수조바닥에 고정되었고 위쪽 고리는 등장력 변환기에 연결되었고 등장력 변환기의 전기적 신호는 생리측정기에 표시되었다. 재미있게도 플로레틴은 수축약 (fluoride, phorbol ester)에 의한 혈관 수축을 억제하여 ROCK 또는 MEK(마이토겐 활성화 단백질 키나제 키나제) 비활성화 같은 경로가 혈관이완에 관여할 수 있음을 보였다. 따라서 phloretin은 내피가 완전한 혈관에서의 내피에 의존적인 작용 외에 추가적으로 내피에 비의존적으로 평활근에서 ROCK 또는 MEK 활성 감소에 참여하여 결과적으로 평활근에서 액틴-미오신 상호작용을 억제하여 혈관을 이완하는 것으로 관찰되었다. 또한 phloretin은 thromboxane A2 유도수축을 억제하고 ROCK 및 MEK 억제를 포함하는 기전있음을 주장합니다.

Rhodanthpyrone A and B play an anti-inflammatory role by suppressing the nuclear factor-κB pathway in macrophages

  • Kim, Kyeong Su;Han, Chang Yeob;Han, Young Taek;Bae, Eun Ju
    • The Korean Journal of Physiology and Pharmacology
    • /
    • 제23권6호
    • /
    • pp.493-499
    • /
    • 2019
  • Macrophage-associated inflammation is crucial for the pathogenesis of diverse diseases including metabolic disorders. Rhodanthpyrone (Rho) is an active component of Gentiana rhodantha, which has been used in traditional Chinese medicine to treat inflammation. Although synthesis procedures of RhoA and RhoB were reported, the biological effects of the specific compounds have never been explored. In this study, the anti-inflammatory activity and mechanisms of action of RhoA and RhoB were studied in lipopolysaccharide (LPS)-stimulated macrophages. Pretreatment with RhoA and RhoB decreased inducible nitric oxide synthase and cyclooxygenase-2 expressions in RAW 264.7 cells and in thioglycollate-elicited mouse peritoneal macrophages. In addition, it downregulated transcript levels of several inflammatory genes in LPS-stimulated RAW 264.7 cells, including inflammatory cytokines/chemokines (Tnfa, Il6, and Ccl2) and inflammatory mediators (Nos2 and Ptgs2). Macrophage chemotaxis was also inhibited by treatment with the compounds. Mechanistic studies revealed that RhoA and RhoB suppressed the nuclear factor $(NF)-{\kappa}B$ pathway, but not the canonical mitogen activated protein kinase pathway, in LPS-stimulated condition. Moreover, the inhibitory effect of RhoA and RhoB on inflammatory gene expressions was attenuated by treatment with an $NF-{\kappa}B$ inhibitor. Our findings suggest that RhoA and RhoB play an anti-inflammatory role at least in part by suppressing the $NF-{\kappa}B$ pathway during macrophage-mediated inflammation.

Luteolin attenuates migration and invasion of lung cancer cells via suppressing focal adhesion kinase and non-receptor tyrosine kinase signaling pathway

  • Masraksa, Wuttipong;Tanasawet, Supita;Hutamekalin, Pilaiwanwadee;Wongtawatchai, Tulaporn;Sukketsiri, Wanida
    • Nutrition Research and Practice
    • /
    • 제14권2호
    • /
    • pp.127-133
    • /
    • 2020
  • BACKGROUND/OBJECTIVES: Non-small cell lung cancer is mostly recognized among other types of lung cancer with a poor prognosis by cause of chemotherapeutic resistance and increased metastasis. Luteolin has been found to decrease cell metastasis. However, its underlying mechanisms remain unresolved. The objective of this study was to examine the effect (and its mechanism) of luteolin on the migration and invasion of human non-small cell lung cancer A549 cells. MATERIALS/METHODS: Cell viability was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Wound healing and transwell assays were evaluated to assess migration and invasion, respectively. Western blot analysis and immunofluorescence were further performed to investigate the role of luteolin and its mechanisms of action. RESULTS: Administration with up to 40 μM luteolin showed no cytotoxic activity on lung cancer A549 cells or non-cancer MRC-5 cells. Additionally, luteolin at 20-40 μM significantly suppressed A549 cells' migration, invasion, and the formation of filopodia in a concentration-dependent manner at 24 h. This is similar with western blot analysis, which revealed diminished the phosphorylated focal adhesion kinase (pFAK), phosphorylated non-receptor tyrosine kinase (pSrc), Ras-related C3 botulinum toxin substrate 1 (Rac1), cell division control protein 42 (Cdc42), and Ras homolog gene family member A (RhoA) expression levels. CONCLUSIONS: Overall, our data indicate that luteolin plays a role in controlling lung cancer cells' migration and invasion via Src/FAK and its downstream Rac1, Cdc42, and RhoA pathways. Luteolin might be considered a promising candidate for suppressing invasion and metastasis of lung cancer cells.

Capsaicin, a component of red peppers, stimulates protein kinase CKII activity

  • Rho, Yun-Wha;Bae, Young-Seuk
    • BMB Reports
    • /
    • 제43권5호
    • /
    • pp.325-329
    • /
    • 2010
  • Protein kinase CKII (CKII), a heterotetramer composed of two catalytic ($\alpha$ or $\alpha$') subunits and two regulatory ($\beta$) subunits, plays a critical role in cell proliferation and anti-apoptosis. Recently, capsaicin was shown to trigger apoptosis. Therefore, we examined the effect of capsaicin on CKII activity. Although capsaicin induced apoptotic death in HeLa cells, CKII activity was increased in the cytosolic fraction of HeLa cells after treatment. Capsaicin did not change the expression of the $CKII{\alpha}$ and $CKII{\beta}$ proteins. Capsaicin stimulated the catalytic activity of recombinant CKII tetramer, but not the $CKII{\alpha}$ subunit. Moreover, capsaicin enhanced the autophosphorylation of $CKII{\alpha}$ and $CKII{\beta}$. Taken together, our data suggest that capsaicin stimulates the phosphotransferase activity of CKII holoenzyme by interacting with the $CKII{\beta}$ subunit.