1.Venous Sinus Thrombosis and Dural Arteriovenous Fistula after Herpes Simplex Encephalitis in a Patient with Protein S, Protein C Deficiency
Yujin SONG ; Hwajin CHOI ; Yunyoung CHOI ; Hyunkyum CHO ; Dongyu KIM ; Yo Han JUNG
Journal of the Korean Neurological Association 2024;42(2):162-165
Herpes simplex encephalitis is known to cause intracranial hypertension and cerebral edema. When cerebral edema occurs, venous sinuses are compressed, resulting in congestion and thrombosis. An arteriovenous fistula may form as a result, particularly in conjunction with superior sagittal sinus thrombosis. In this report, the authors describe a patient with protein S and C deficiency who developed venous sinus thrombosis and dural arteriovenous fistula after experiencing herpes simplex encephalitis.
2.FK506 reduces calpain-regulated calcineurin activity in both the cytoplasm and the nucleus.
Sun Hee LEE ; Jungil CHOI ; Hwajin KIM ; Dong Hoon LEE ; Gu Seob ROH ; Hyun Joon KIM ; Sang Soo KANG ; Wan Sung CHOI ; Gyeong Jae CHO
Anatomy & Cell Biology 2014;47(2):91-100
Excessive immune responses induced by ischemia-reperfusion injury (IRI) are known to lead to necrotic and apoptotic cell death, and calcineurin plays a major role in this process. Calcineurin dephosphorylates the nuclear factor of activated T-cells (NFAT), permitting its translocation into the nucleus. As a result, calcineurin promotes the release of pro-inflammatory cytokines, such as tumor necrosis factor-alpha. The overproduction of pro-inflammatory cytokines causes renal cell death. Calcineurin activity is regulated by calpain, a cysteine protease present in the nucleus. Calpain-mediated proteolysis increases the phosphatase activity of calcineurin, resulting in NFAT dephosphorylation. This process has been studied in cardiomyocytes but its role in renal IRI is unknown. Thus, we examined whether calpain regulates calcineurin in renal tubule nuclei. We established an in vivo renal IRI model in mice and identified the protective role of a calcineurin inhibitor, FK506, in this process. Calcineurin is expressed in the nucleus, where it is present in its calpain-cleaved form. FK506 reduced nuclear expression of calcineurin and prevented calcineurin-mediated NFAT activation. Our study shows clearly that FK506 reduces calpain-mediated calcineurin activity. Consequently, calcineurin could not maintain NFAT activation. FK506 reduced renal cell death by suppressing the transcription of pro-inflammatory cytokine genes. This study provides evidence that FK506 protects against inflammation in a renal IRI mouse model. We also provided a mechanism of calcineurin action in the nucleus. Therefore, FK506 could improve renal function by decreasing calcineurin activity in both the cytoplasm and the nucleus of renal tubule cells.
Animals
;
Calcineurin*
;
Calpain
;
Cell Death
;
Cysteine Proteases
;
Cytokines
;
Cytoplasm*
;
Inflammation
;
Mice
;
Myocytes, Cardiac
;
Proteolysis
;
Reperfusion Injury
;
T-Lymphocytes
;
Tacrolimus*
;
Tumor Necrosis Factor-alpha
3.FK506 reduces calpain-regulated calcineurin activity in both the cytoplasm and the nucleus.
Sun Hee LEE ; Jungil CHOI ; Hwajin KIM ; Dong Hoon LEE ; Gu Seob ROH ; Hyun Joon KIM ; Sang Soo KANG ; Wan Sung CHOI ; Gyeong Jae CHO
Anatomy & Cell Biology 2014;47(2):91-100
Excessive immune responses induced by ischemia-reperfusion injury (IRI) are known to lead to necrotic and apoptotic cell death, and calcineurin plays a major role in this process. Calcineurin dephosphorylates the nuclear factor of activated T-cells (NFAT), permitting its translocation into the nucleus. As a result, calcineurin promotes the release of pro-inflammatory cytokines, such as tumor necrosis factor-alpha. The overproduction of pro-inflammatory cytokines causes renal cell death. Calcineurin activity is regulated by calpain, a cysteine protease present in the nucleus. Calpain-mediated proteolysis increases the phosphatase activity of calcineurin, resulting in NFAT dephosphorylation. This process has been studied in cardiomyocytes but its role in renal IRI is unknown. Thus, we examined whether calpain regulates calcineurin in renal tubule nuclei. We established an in vivo renal IRI model in mice and identified the protective role of a calcineurin inhibitor, FK506, in this process. Calcineurin is expressed in the nucleus, where it is present in its calpain-cleaved form. FK506 reduced nuclear expression of calcineurin and prevented calcineurin-mediated NFAT activation. Our study shows clearly that FK506 reduces calpain-mediated calcineurin activity. Consequently, calcineurin could not maintain NFAT activation. FK506 reduced renal cell death by suppressing the transcription of pro-inflammatory cytokine genes. This study provides evidence that FK506 protects against inflammation in a renal IRI mouse model. We also provided a mechanism of calcineurin action in the nucleus. Therefore, FK506 could improve renal function by decreasing calcineurin activity in both the cytoplasm and the nucleus of renal tubule cells.
Animals
;
Calcineurin*
;
Calpain
;
Cell Death
;
Cysteine Proteases
;
Cytokines
;
Cytoplasm*
;
Inflammation
;
Mice
;
Myocytes, Cardiac
;
Proteolysis
;
Reperfusion Injury
;
T-Lymphocytes
;
Tacrolimus*
;
Tumor Necrosis Factor-alpha
4.Myeloid-specific SIRT1 Deletion Aggravates Hepatic Inflammation and Steatosis in High-fat Diet-fed Mice.
Kyung Eun KIM ; Hwajin KIM ; Rok Won HEO ; Hyun Joo SHIN ; Chin Ok YI ; Dong Hoon LEE ; Hyun Joon KIM ; Sang Soo KANG ; Gyeong Jae CHO ; Wan Sung CHOI ; Gu Seob ROH
The Korean Journal of Physiology and Pharmacology 2015;19(5):451-460
Sirtuin 1 (SIRT1) is a mammalian NAD+-dependent protein deacetylase that regulates cellular metabolism and inflammatory response. The organ-specific deletion of SIRT1 induces local inflammation and insulin resistance in dietary and genetic obesity. Macrophage-mediated inflammation contributes to insulin resistance and metabolic syndrome, however, the macrophage-specific SIRT1 function in the context of obesity is largely unknown. C57/BL6 wild type (WT) or myeloid-specific SIRT1 knockout (KO) mice were fed a high-fat diet (HFD) or normal diet (ND) for 12 weeks. Metabolic parameters and markers of hepatic steatosis and inflammation in liver were compared in WT and KO mice. SIRT1 deletion enhanced HFD-induced changes on body and liver weight gain, and increased glucose and insulin resistance. In liver, SIRT1 deletion increased the acetylation, and enhanced HFD-induced nuclear translocation of nuclear factor kappa B (NF-kappaB), hepatic inflammation and macrophage infiltration. HFD-fed KO mice showed severe hepatic steatosis by activating lipogenic pathway through sterol regulatory element-binding protein 1 (SREBP-1), and hepatic fibrogenesis, as indicated by induction of connective tissue growth factor (CTGF), alpha-smooth muscle actin (alpha-SMA), and collagen secretion. Myeloid-specific deletion of SIRT1 stimulates obesity-induced inflammation and increases the risk of hepatic fibrosis. Targeted induction of macrophage SIRT1 may be a good therapy for alleviating inflammation-associated metabolic syndrome.
Acetylation
;
Actins
;
Animals
;
Collagen
;
Connective Tissue Growth Factor
;
Diet
;
Diet, High-Fat
;
Fibrosis
;
Glucose
;
Inflammation*
;
Insulin Resistance
;
Liver
;
Macrophages
;
Metabolism
;
Mice*
;
NF-kappa B
;
Obesity
;
Sirtuin 1
;
Sterol Regulatory Element Binding Protein 1
;
Weight Gain