Nur77 upregulates HIF-alpha by inhibiting pVHL-mediated degradation

In this study, we investigated the role of Nur77, an orphan nuclear receptor, in HIF-alpha transcriptional activity. We found that Nur77 associates and stabilizes HIF-1alpha via indirect interaction. Nur77 was found to interact with pVHL in vivo via the alpha-domain of pVHL. By binding to pVHL, Nur77 competed with elongin C for pVHL binding. Moreover, Nur77-binding to pVHL inhibited the pVHL-mediated ubiquitination of HIF-1alpha and ultimately increased the stability and transcriptional activity of HIF-1alpha. The ligand-binding domain of Nur77 was found to interact with pVHL and the expression of this ligand-binding domain was sufficient to stabilize and transactivate HIF-1alpha. Under the conditions that cobalt chloride was treated or pVHL was knocked down, Nur77 could not stabilize HIF-alpha. Moreover, Nur77 could not further stabilize HIF-2alpha in A498/VHL stable cells, which is consistent with our finding that Nur77 indirectly stabilizes HIF-alpha by binding to pVHL. Thus, our results suggest that an orphan nuclear receptor Nur77 binds to pVHL, thereby stabilizes and increases HIF-alpha transcriptional activity under the non- hypoxic conditions.

Menin represses JunD transcriptional activity in protein kinase Ctheta-mediated Nur77 expression

TCR signaling leading to thymocyte apoptosis is mediated through the expression of the Nur77 family of orphan nuclear receptors. It has been shown that the Nur77 promoter is activated by at least two signaling pathways, one mediated by calcium and the other by protein kinase C (PKC). MEF2D has been known to regulate Nur77 expression in a calcium- dependent manner. The mechanism by which calcium regulates MEF2D is through dissociation of calcium-sensitive MEF2 corepressors (Cabin1/ HDACs, HDAC4/5) and the association with calcineurin-activated transcription factor NF-AT and the coactivator p300. However, little is known about how PKC activates the Nur77 promoter. Herein, we report that PKC theta targets AP-1 like response element in the Nur77 promoter where JunD constitutively binds. PKC theta triggers mitogen-activated protein kinase- inediated phosphorylation of JunD, and increases transcriptional activity of JunD, cooperatively with p300. Menin is identified as the transcriptional corepressor for JunD via recruitment of mSin3-istone deacetylases. In fact, Menin represses PKC theta/ p300-mediated transcriptional activity of JunD in T cell. Its dynamic regulation of histone modifiers with JunD is responsible for PKCq-synergistic effect on Nur77 expression in T cell.

Complex Regional Pain Syndrome after Wedge Resection of Apex of Lung / 대한흉부외과학회지

Complex regional pain syndrome is pain disorder which is characterized by aching pain, marked painful sensation, hypothermesthesia, vasomotor dysfunction, hyperhidrosis, impairment of motor function, trophic changes of distal part of not-operated extremity after trauma and operation. Pain produce increased sensitivity to catecholamine and diagnosed by infra red thermography and Treatment consists of pain relief and rehabilitational therapy for functional restoration of affected limb. We experienced a case of complex regional pain syndrome in a 16-year-old man after wedge resection of pulmonary apex for bullae and report this case with a review of the literature.

Respiratory Assist by Use of Electrical Diaphragmatic Pacing / 대한흉부외과학회지

BACKGROUND: Electrical breathing pacing has many advantages over mechanical ventilation. However, clinically permanent diaphragmatic pacing has been applied to limited patients and few temporary pacing has been reported. Our purpose is to investigate the feasibility of temporary electrical diaphragm pacing in explothoracotomy canine cases. METHODS: Five dogs were studied under the general anesthesia. Left 5th intercostal space was opened. Self designed temporary pacing leads were placed around the left phrenic nerve and connected to the myostimulator. Chest wall was closed after tube insertion with underwater drainage. Millar catheter was introduced to the aorta and right atrium. Swan-Ganz catheter was introduced to the pulmonary artery. When the self respiration was shallow with deep anesthesia, hemodynamic and tidal volume were measured with the stimulator on. RESULTS: Tidal volume increased from 143.3 +/- 51.3 ml to 272.3 +/- 87.4 ml(p=0.004). Right atrial diastolic pressure decreased from 0.7 +/- 4.0 mmHg to -10.5 +/- 4.7 mmHg(p=0.005). Pulmonary arterial diastolic pressure decreased from 6.1 +/- 2.5 mmHg to 1.2 +/- 4.8 mmHg(p<0.001). The height of water level in chest tube to show intrathoracic pressure change was from 10.3 +/- 6.7cmH2O to 20.0 +/- 5.3 cmH2O. CONCLUSION: Temporary electrical diaphragmatic pacing is a simple method to assist respiration in explothoracotomy canine cases. Self designed pacing lead is implantable and removable. Negative pressure ventilation has favorable effects on the circulatory system. Therefore, clinical application of temporary breathing pacing is feasible in thoracotomy patients to assist cardiorespiratory function.

Sclerotherapy of the Varicose Veins / 대한흉부외과학회지

BACKGROUND: Sclerotherapy has been introduced as a new treatment modality of varicose vein. MATERIAL AND METHOD: Ninety-four patients with the diagnosis of varicose vein were treated with sclerotherapy at Yongdong Severance Hospital, Yonsei University Medical College from September, 1997 to August, 1999. History taking, physical examinations and laboratory examinations were performed. The short term outcome and the complications were reviewed. RESULT: The age of the patients were ranged from 20 to 70 years with the mean age of 43.4 years. All the patients(28 men, 66 women) had protruding superficial leg veins and 2 local pain, 2 fatigue, 1 heaviness. Complications were fever, phlebitis and ulceration. Fifty patients were satisfied after 1 procedure. CONCLUSION: Sclerotherapy is an effective treatment modality with cosmetic superiority for the patients with varicose veins.