Phosphorylation of DYNLT1 at Serine 82 Regulates Microtubule Stability and Mitochondrial Permeabilization in Hypoxia

Xue Xu,Yue-sheng Huang,Qiong Zhang,Jiong-yu Hu,Dong-xia Zhang2,Xu-pin Jiang,jie-zhi Jia,Jing-ci Zhu 한국분자세포생물학회 2013 Molecules and cells Vol.36 No.4

Hypoxia-induced microtubule disruption and mitochondrial permeability transition (mPT) are crucial events leading to fatal cell damage and recent studies showed that microtubules (MTs) are involved in the modulation of mitochondrial function. Dynein light chain Tctex-type 1 (DYNLT1) is thought to be associated with MTs and mitochondria. Previously we demonstrated that DYNLT1 knockdown aggravates hypoxia-induced mitochondrial permeabilization, which indicates a role of DYNLT1 in hypoxic cytoprotection. But the underlying regulatory mechanism of DYNLT1 remains illusive. Here we aimed to investigate the phosphorylation alteration of DYNLT1 at serine 82 (S82) in hypoxia (1% O2). We therefore constructed recombinant adenoviruses to generate S82E and S82A mutants, used to transfect H9c2 and HeLa cell lines. Development of hypoxia-induced mPT (MMP examining, Cyt c release and mPT pore opening assay), hypoxic energy metabolism (cellular viability and ATP quantification), and stability of MTs were examined. Our results showed that phosph-S82 (S82-P) expression was increased in early hypoxia; S82E mutation (phosphomimic) aggravated mitochondrial damage, ele-vated the free tubulin in cytoplasm and decreased the cellular viability; S82A mutation (dephosphomimic) seemed to diminish the hypoxia-induced injury. These data suggest that DYNLT1 phosphorylation at S82 is involved in MTs and mitochondria regulation, and their interaction and cooperation contribute to the cellular hypoxic tolerance. Thus, we provide new insights into a DYNLT1 mechanism in stabilizing MTs and mitochondria, and propose a potential therapeutic target for hypoxia cytoprotective studies.

Erratum to: The treatment effect of novel hGHRH homodimer to male infertility hamster

Zhang, Xu-Dong,Guo, Xiao-Yuan,Tang, Jing-Xuan,Yue, Lin-Na,Zhang, Juan-Hui,Liu, Tao,Dong, Yu-Xia,Tang, Song-Shan The Korean Society of Pharmacology 2019 The Korean Journal of Physiology & Pharmacology Vol.23 No.1

The treatment effect of novel hGHRH homodimer to male infertility hamster

Zhang, Xu-Dong,Guo, Xiao-Yuan,Tang, Jing-Xuan,Yue, Lin-Na,Zhang, Juan-Hui,Liu, Tao,Dong, Yu-Xia,Tang, Song-Shan The Korean Society of Pharmacology 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.6

Extra-hypothalamic growth hormone-releasing hormone (GHRH) plays an important role in reproduction. To study the treatment effect of Grin (a novel hGHRH homodimer), the infertility models of 85 male Chinese hamsters were established by intraperitoneally injecting 20 mg/kg of cyclophosphamide once in a week for 5 weeks and the treatment with Grin or human menopausal gonadotropin (hMG) as positive control was evaluated by performing a 3-week mating experiment. 2-8 mg/kg of Grin and 200 U/kg of hMG showed similar effect and different pathological characteristics. Compared to the single cyclophosphamide group (0%), the pregnancy rates (H-, M-, L-Grin 26.7, 30.8, 31.3%, and hMG 31.3%) showed significant difference, but there was no difference between the hMG and Grin groups. The single cyclophosphamide group presented loose tubules with pathologic vacuoles and significant TUNEL positive cells. Grin induced less weight of body or testis, compactly aligned tubules with little intra-lumens, whereas hMG caused more weight of body or testis, enlarging tubules with annular clearance. Grin presented a dose-dependent manner or cell differentiation-dependentincrease in testicular GHRH receptor, and did not impact the levels of blood and testicular GH, testosterone. Grin promotes fertility by proliferating and differentiating primitive cells through up-regulating testicular GHRH receptor without triggering GH secretion, which might solve the etiology of oligoasthenozoospermia.

The TL1A-DR3 Axis in Asthma: Membrane-Bound and Secreted TL1A Co-Determined the Development of Airway Remodeling

Zhang Jintao,Zhang Dong,Pan Yun,Liu Xiaofei,Xu Jiawei,Qiao Xinrui,Cui Wenjing,Dong Liang 대한천식알레르기학회 2022 Allergy, Asthma & Immunology Research Vol.14 No.2

Purpose: Tumor necrosis factor-like ligand 1A (TL1A), especially its secreted form, has been shown to contribute to eosinophilic inflammation and mucus production, cardinal features of asthma, through its receptor, death receptor 3 (DR3). However, the role of the TL1A-DR3 axis in asthma, especially in terms of airway remodeling, has not yet been fully understood. Methods: The present study investigated the expression and secretion of TL1A in the lung and human bronchial epithelial cells. DR3 small interfering RNA (siRNA), TL1A siRNA, and truncated plasmids were used respectively to identify the function of the TL1A-DR3 axis in vitro. To further validate the roles of the TL1A-DR3 axis in asthma, we collected airway biopsies and sputa from asthmatic patients and constructed a mouse model following rTL1A administration, DR3 knockdown, and TL1A knockout, the asthma-related inflammatory response and the pathological changes in airways were analyzed using various experimental methods. Associated signaling pathways downstream of TL1A knockout in the mouse model were analyzed using RNA sequencing. Results: TL1A, especially its non-secreted form (nsTL1A) was involved in the remodeling process in asthmatics’ airways. Knockdown of TL1A or its receptor DR3 decreased the expression of fibrosis-associated protein in BEAS-2B cells. Reversely, overexpression of nsTL1A in airway epithelial cells facilitated the transforming growth factor-β-induced remodeling progress. In the asthma mouse model, activating the TL1A-DR3 axis contributes to airway inflammation, remodeling, and tissue destruction. Reciprocally, DR3 knockdown or TL1A knockout partly reverses airway remodeling in the asthma model induced by ovalbumin. Conclusions: Our results confirm differential TL1A expression (including its secreted and non-secreted form) in asthma, which modulates remodeling. The shared mechanism of action by which nsTL1A and secreted TL1A exert their effects on asthma development might be mediated via the nuclear factor-κB pathway. The TL1A-DR3 axis presents a promising therapeutic target in asthma.

MSP58 Knockdown Inhibits the Proliferation of Esophageal Squamous Cell Carcinoma in Vitro and in Vivo

Xu, Chun-Sheng,Zheng, Jian-Yong,Zhang, Hai-Long,Zhao, Hua-Dong,Zhang, Jing,Wu, Guo-Qiang,Wu, Lin,Wang, Qing,Wang, Wei-Zhong,Zhang, Jian Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.7

Esophageal carcinoma (EC) is one of the most aggressive cancers with a poor prognosis. Understanding the molecular mechanisms underlying esophageal cancer progression is a high priority for improved EC diagnosis and prognosis. Recently, MSP58 was shown to behave as an oncogene in colorectal carcinomas and gliomas. However, little is known about its function in esophageal carcinomas. We therefore examined the effects of MSP58 knockdown on the growth of esophageal squamous cell carcinoma (ESCC) cells in vitro and in vivo in order to gain a better understanding of its potential as a tumor therapeutic target. We employed lentiviral-mediated small hairpin RNA (shRNA) to knock down the expression of MSP58 in the ESCC cell lines Eca-109 and EC9706 and demonstrated inhibition of ESCC cell proliferation and colony formation in vitro. Furthermore, flow cytometry and western blot analyses revealed that MSP58 depletion induced cell cycle arrest by regulating the expression of P21, CDK4 and cyclin D1. Notably, the downregulation of MSP58 significantly inhibited the growth of ESCC xenografts in nude mice. Our results suggest that MSP58 may play an important role in ESCC progression.

C-type natriuretic peptide attenuates renal osteodystrophy through inhibition of FGF-23/MAPK signaling

Dong Dong Zhang,Yang Fang Wu,Wei Xia Chen,Yao Xu,Si Yan Liu,Huang Huang Luo,Guang Mei Jiang,Yue Wu,Peng Hu 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

Renal osteodystrophy (ROD) occurs as early as chronic kidney disease (CKD) stage 2 and seems ubiquitous in almost all pediatric patients with CKD stage 5. Fibroblast growth factor (FGF)-23, a bone-derived endocrine regulator of phosphate homeostasis, is overexpressed in CKD and disturbs osteoblast differentiation and matrix mineralization. In contrast, C-type natriuretic peptide (CNP) acts as a potent positive regulator of bone growth. In the present study, we infused CNP into uremic rats and observed whether CNP could attenuate ROD through the inhibition of FGF-23 cascades. In uremic rats, CNP administration significantly alleviated renal dysfunction, calcium phosphate metabolic disorders, hypovitaminosis D, secondary hyperparathyroidism, the decrease in bone turnover markers and retarded bone pathological progression. More importantly, within FGF-23/mitogen-activated protein kinase (MAPK) signaling, the fibroblast growth factor receptor-1, Klotho and alternative (STAT-1/phospho-STAT-1) elements were upregulated by CNP, whereas FGF-23, RAF-1/phospho-RAF-1, and downstream (ERK/phospho-ERK and P38/phospho-P38) elements were paradoxically underexpressed in bone tissue. Therefore, CNP exerts a therapeutic effect on ROD through inhibition of FGF-23/MAPK signaling at the RAF-1 level.

Autophagy in Tumorigenesis and Cancer Treatment

Xu, Dong-Wei,Zhang, Guan-Qing,Wang, Zong-Wei,Xu, Xiao-Yin,Liu, Tong-Xiang Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.6

Autophagy is a self-digestion process, wrapping cytoplasmic proteins or organelles to form vesicles for degradation in lysosomes. The process plays an important role in the maintenance of intracellular homostasis. Here we overview articles on autophagy and cancer/tumors in Pubmed and found 327 articles. Autophagy exists in many tumors and is involved in cell malignant transformation and tumor cell growth. In early phases of tumorigenesis, autophagy clears the abnormally folded proteins and dysfunctional organelles such as mitochondria. Autophagy can also inhibit cell stress responses and prevent genetic damage. When a tumor develops, autophagy helps tumor cells survive nutritional deficiencies and hypoxic conditions. Studies of autophagy in the occurrence and progression of tumors should provide new therapeutic strategies for tumors.

The treatment effect of novel hGHRH homodimer to male infertility hamster

Xu-Dong Zhang,Xiao-Yuan Guo,Jing-Xuan Tang,Lin-Na Yue,Juan-Hui Zhang,Tao Liu,Yu-Xia Dong,Song-Shan Tang 대한생리학회-대한약리학회 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.6

Extra-hypothalamic growth hormone-releasing hormone (GHRH) plays an important role in reproduction. To study the treatment effect of Grin (a novel hGHRH homodimer), the infertility models of 85 male Chinese hamsters were established by intraperitoneally injecting 20 mg/kg of cyclophosphamide once in a week for 5 weeks and the treatment with Grin or human menopausal gonadotropin (hMG) as positive control was evaluated by performing a 3-week mating experiment. 2-8 mg/kg of Grin and 200 U/kg of hMG showed similar effect and different pathological characteristics. Compared to the single cyclophosphamide group (0%), the pregnancy rates (H-, M-, L-Grin 26.7, 30.8, 31.3%, and hMG 31.3%) showed significant difference, but there was no difference between the hMG and Grin groups. The single cyclophosphamide group presented loose tubules with pathologic vacuoles and significant TUNEL positive cells. Grin induced less weight of body or testis, compactly aligned tubules with little intra-lumens, whereas hMG caused more weight of body or testis, enlarging tubules with annular clearance. Grin presented a dose-dependent manner or cell differentiation-dependentincrease in testicular GHRH receptor, and did not impact the levels of blood and testicular GH, testosterone. Grin promotes fertility by proliferating and differentiating primitive cells through up-regulating testicular GHRH receptor without triggering GH secretion, which might solve the etiology of oligoasthenozoospermia.

Culture of a Whole Porcine Liver Ex Situ without Red Blood Cells

( Jing Dong ),( Lingling Xia ),( Hefang Shen ),( Congwen Bian ),( Sujin Bao ),( Ming Zhang ),( Yan Dai ),( Yanhong Xu ),( Qiru Xiong ),( Jianjian Xu ),( Lili Xu ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Liver transplantation is an effective approach to end-stage liver disease. Shortage of donor liver and increased waiting time for liver transplantation necessitate the development of an organ culture system by which livers can be cultured and maintained ex situ for a prolonged period of time. The aim of this work is to test whether cell culture condition in vitro could be used to culture whole livers ex situ without the use of erythrocytes. Methods: Eight castrated male land race/farm young porcine livers were exposed to 30 min warm ischemia and 30 min cold perfusion. Livers were isolated and connected to an ex situ liver culture system using a standard culture medium RPMI 1640 supplied with 10% of fetal calf serum and sufficient dissolved oxygen under a normothermic condition for 6 hours. Metabolic biomarkers, bile and urea production, hepatic cell viability, and histology analysis of biopsies were performed and analyzed. Results: Dissociated porcine hepatic cells survived and grew in vitro under the standard RPMI 1640 culture medium. When the same RPMI 1640 medium supplemented with 10% of FCS and sufficient oxygen was used to culture livers ex situ, over 98% of liver cells were viable for at least 6 hours during ex situ whole organ culture based on the results from biochemical assays. Conclusions: Our data demonstrate that the liver culture system established in this work can be used to culture whole livers ex situ in the absence of erythrocytes.

Distributed Consensus Control for Automatic Gauge Control of Hot Strip Mills

Xiao-Dong Zhang,Shao-Shu Gao,Wei-Xi Gao,Xu-Ying Wang,Wei Zhang 제어·로봇·시스템학회 2021 International Journal of Control, Automation, and Vol.19 No.5

In this study, the distributed control strategy is proposed for the automatic gauge control(AGC) system, which is a typical multi-agent system. The distributed control protocol is developed with the subspace identification method using the measurements of the local agent and its neighbors directly,without any knowledge of the AGC system dynamics. The stability analysis of the multi-agent system with the proposed control protocol is given. In addition, the consensus control protocol with communication time delay is investigated. Finally, simulation results are carried out to verify the feasibility and effectiveness of the proposed control strategy.