Caveolin‐1 deficiency induces premature senescence with mitochondrial dysfunction

Yu, Dong&#x2010,Min,Jung, Seung Hee,An, Hyoung&#x2010,Tae,Lee, Sungsoo,Hong, Jin,Park, Jun Sub,Lee, Hyun,Lee, Hwayeon,Bahn, Myeong&#x2010,Suk,Lee, Hyung Chul,Han, Na‐,Kyung,Ko, Jesang,Lee, Jae&# BLACKWELL PUBLISHING 2017 AGING CELL Vol.16 No.4

<P><B>Summary</B></P><P>Paradoxical observations have been made regarding the role of caveolin‐1 (Cav‐1) during cellular senescence. For example, caveolin‐1 deficiency prevents reactive oxygen species‐induced cellular senescence despite mitochondrial dysfunction, which leads to senescence. To resolve this paradox, we re‐addressed the role of caveolin‐1 in cellular senescence in human diploid fibroblasts, A549, HCT116, and Cav‐1<SUP><I>−/−</I></SUP> mouse embryonic fibroblasts. Cav‐1 deficiency (knockout or knockdown) induced cellular senescence via a p53‐p21‐dependent pathway, downregulating the expression level of the cardiolipin biosynthesis enzymes and then reducing the content of cardiolipin, a critical lipid for mitochondrial respiration. Our results showed that Cav‐1 deficiency decreased mitochondrial respiration, reduced the activity of oxidative phosphorylation complex I (CI), inactivated SIRT1, and decreased the NAD<SUP>+</SUP>/NADH ratio. From these results, we concluded that Cav‐1 deficiency induces premature senescence via mitochondrial dysfunction and silent information regulator 2 homologue 1 (SIRT1) inactivation.</P>

QTL mapping and GWAS reveal candidate genes controlling capsaicinoid content in <i>Capsicum</i>

Han, Koeun,Lee, Hea&#x2010,Young,Ro, Na‐,Young,Hur, On&#x2010,Sook,Lee, Joung&#x2010,Ho,Kwon, Jin&#x2010,Kyung,Kang, Byoung&#x2010,Cheorl John Wiley and Sons Inc. 2018 Plant biotechnology journal Vol.16 No.9

<P><B>Summary</B></P><P>Capsaicinoids are unique compounds produced only in peppers (<I>Capsicum</I> spp.). Several studies using classical quantitative trait loci (QTLs) mapping and genomewide association studies (GWAS) have identified QTLs controlling capsaicinoid content in peppers; however, neither the QTLs common to each population nor the candidate genes underlying them have been identified due to the limitations of each approach used. Here, we performed QTL mapping and GWAS for capsaicinoid content in peppers using two recombinant inbred line (RIL) populations and one GWAS population. Whole‐genome resequencing and genotyping by sequencing (GBS) were used to construct high‐density single nucleotide polymorphism (SNP) maps. Five QTL regions on chromosomes 1, 2, 3, 4 and 10 were commonly identified in both RIL populations over multiple locations and years. Furthermore, a total of 109 610 SNPs derived from two GBS libraries were used to analyse the GWAS population consisting of 208 <I>C. annuum</I>‐clade accessions. A total of 69 QTL regions were identified from the GWAS, 10 of which were co‐located with the QTLs identified from the two biparental populations. Within these regions, we were able to identify five candidate genes known to be involved in capsaicinoid biosynthesis. Our results demonstrate that QTL mapping and GBS‐GWAS represent a powerful combined approach for the identification of loci controlling complex traits.</P>

22‐ S ‐Hydroxycholesterol protects against ethanol‐induced liver injury by blocking the auto/paracrine activation of MCP ‐1 mediated by LXRα

Na, Tae&#x2010,Young,Han, Young&#x2010,Hyun,Ka, Na‐,Lee,Park, Han&#x2010,Su,Kang, Yun Pyo,Kwon, Sung Won,Lee, Byung&#x2010,Hoon,Lee, Mi&#x2010,Ock John WileySons, Ltd 2015 The Journal of pathology Vol.235 No.5

<P><B>Abstract</B></P><P>Chronic ethanol consumption causes hepatic steatosis and inflammation, which are associated with liver hypoxia. Monocyte chemoattractant protein‐1 (MCP‐1) is a hypoxia response factor that determines recruitment and activation of monocytes to the site of tissue injury. The level of MCP‐1 is elevated in the serum and liver of patients with alcoholic liver disease (ALD); however, the molecular details regarding the regulation of MCP‐1 expression are not yet understood completely. Here, we show the role of liver X receptor α (LXRα) in the regulation of MCP‐1 expression during the development of ethanol‐induced fatty liver injury, using an antagonist, 22‐S‐hydroxycholesterol (22‐S‐HC). First, administration of 22‐S‐HC attenuated the signs of liver injury with decreased levels of MCP‐1 and its receptor CCR2 in ethanol‐fed mice. Second, hypoxic conditions or treatment with the LXRα agonist GW3965 significantly induced the expression of MCP‐1, which was completely blocked by treatment with 22‐S‐HC or infection by shLXRα lentivirus in the primary hepatocytes. Third, over‐expression of LXRα or GW3965 treatment increased MCP‐1 promoter activity by increasing the binding of hypoxia‐inducible factor‐1α to the hypoxia response elements, together with LXRα. Finally, treatment with recombinant MCP‐1 increased the level of expression of LXRα and LXRα‐dependent lipid droplet accumulation in both hepatocytes and Kupffer cells. These data show that LXRα and its ligand‐induced up‐regulation of MCP‐1 and MCP‐1‐induced LXRα‐dependent lipogenesis play a key role in the autocrine and paracrine activation of MCP‐1 in the pathogenesis of alcoholic fatty liver disease, and that this activation may provide a promising new target for ALD therapy.Copyright © 2014 The Authors. <I>The Journal of Pathology</I> published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.</P>

Effects of FGF 21‐secreting adipose‐derived stem cells in thioacetamide‐induced hepatic fibrosis

Kang, Hwansu,Seo, Eunhui,Park, Jong&#x2010,Moon,Han, Na‐,Young,Lee, Hookeun,Jun, Hee&#x2010,Sook John Wiley and Sons Inc. 2018 JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Vol.22 No.10

<P><B>Abstract</B></P><P>Mesenchymal stem cells (MSCs) have been investigated to treat liver diseases, but the efficiency of MSCs to treat chronic liver diseases is conflicting. FGF21 can reduce inflammation and fibrosis. We established FGF21‐secreting adipose derived stem cells (FGF21_ADSCs) to enhance the effects of ADSCs and transplanted them into thioacetamide (TAA)‐induced liver fibrosis mice via the tail vein. Transplantation of FGF21_ADSCs significantly improved liver fibrosis by decreasing serum hyaluronic acid and reducing the expression of fibrosis‐related factors such as α‐smooth muscle actin (α‐SMA), collagen and tissue inhibitor of metalloproteinase‐1 (TIMP‐1) compared with the Empty_ADSCs by inhibition of p‐JNK, NF‐κB and p‐Smad2/3 signalling. α‐lactoalbumin (LA) and lactotransferrin (LTF), secretory factors produced from FGF21_ADSCs inhibited TGF‐β1‐induced expression of α‐SMA and collagen in LX‐2 cells. These results suggest that transplantation of FGF21_ADSCs inhibited liver fibrosis more effectively than Empty_ADSCs, possibly via secretion of α‐LA and LTF.</P>

Altered expression of melanocortin‐1 receptor (MC1R) in a yellow‐coloured wild raccoon dog (<i>Nyctereutes procyonoides</i>)

Han, Jae&#x2010,Ik,Yang, Hyun,Jeung, Eui&#x2010,Bae,Na, Ki&#x2010,Jeong Blackwell Publishing Ltd 2012 Veterinary dermatology Vol.23 No.3

<P><B>Background – </B> The melanocortin 1 receptor (<I>MC1R</I>) gene plays a key role in determining coat colour in mammals by controlling the proportion of eumelanin and pheomelanin granules. Wild raccoon dogs have a mixed coat colour, with black to brown and grey hairs.</P><P><B>Hypothesis/Objectives – </B> The study was performed to identify the cause of the variant yellow coat colour in a wild raccoon dog.</P><P><B>Animals – </B> A wild raccoon dog that showed coat colour change to yellow and four wild‐type raccoon dogs that showed normal coat colour were included.</P><P><B>Methods – </B> To identify the cause of the variant yellow coat colour, we examined the sequence of the <I>MC1R</I> gene and its expression at the mRNA and protein levels.</P><P><B>Results – </B> The coding region of the <I>MC1R</I> gene of this raccoon dog comprised 954 bp, the same as for wild‐type raccoon dogs and domestic dogs. By comparing the gene with that in the wild‐type raccoon dog, a 2 bp deletion was detected in the 5′‐untranslated region, positioned 152 bp upstream of the start codon. However, there was no significant difference in the mRNA expression level. The yellow raccoon dog revealed a significantly decreased MC1R protein level compared with the wild‐type raccoon dogs, indicating an increase in pheomelanin synthesis.</P><P><B>Conclusions and clinical importance – </B> These results suggest that the variant coat colour in the yellow raccoon dog was associated with decreased MC1R function.</P>

Effect of massage therapy by VOSKIN 125+ painkiller® on inflammatory skin lesions

Han, Na‐,Ra,Moon, Phil&#x2010,Dong,Yoou, Myoung&#x2010,schook,Chang, Tae&#x2010,soun,Kim, Hyung&#x2010,Min,Jeong, Hyun&#x2010,Ja John Wiley Sons, Inc. 2018 Dermatologic therapy Vol.31 No.5

Kanamycin activates caspase‐1 in NC/Nga mice

Han, Na‐,Ra,Kim, Hyung&#x2010,Min,Jeong, Hyun&#x2010,Ja Blackwell Publishing Ltd 2011 Experimental dermatology Vol.20 No.8

<P><B>Abstract: </B> Abuse of antibiotics to treat children has been associated with an increased risk of the development of inflammatory diseases. The underlying mechanism behind this association still remains to be clarified. Here, we examined the mechanisms behind kanamycin‐induced skin inflammation in NC/Nga mice. NC/Nga mice were orally administered kanamycin for 7 days consecutively. Blood, spleen and dorsal skin were taken 18 weeks after kanamycin treatment was stopped. Kanamycin significantly increased the allergic reaction. We also observed significant increases in caspase‐1 mRNA and protein expression in the dorsal skin of the kanamycin‐administered mice compared to the control mice. The increased enzymatic activity of caspase‐1 in the dorsal skin of the kanamycin‐administered mice increased the mRNA expressions of IL‐1β and IL‐18. The productions of IL‐1β and IL‐18 were also increased in the splenocytes obtained from kanamycin‐administered mice. Kanamycin upregulated the TNF‐α mRNA expression in the dorsal skin and the TNF‐α production in stimulated splenocytes. The activation of nuclear factor‐κB and degradation of IκBα were increased by kanamycin administration. Our findings suggest that the use of kanamycin during infancy may increase the potential for skin inflammatory reactions through the upregulation of caspase‐1.</P>

Madi‐Ryuk and its active compound tannic acid suppress allergic inflammatory reactions in activated human mast cell HMC‐1

Kim, Hee&#x2010,Yun,Jeong, Hyun&#x2010,Ja,Han, Na‐,Ra,Jang, Jae&#x2010,Bum,Kim, Hyung&#x2010,Min Wiley (Blackwell Publishing) 2018 Journal of Food Biochemistry Vol.42 No.6

Liver‐Specific and Echogenic Hyaluronic Acid Nanoparticles Facilitating Liver Cancer Discrimination

Min, Hyun Su,Son, Sejin,Lee, Tae Woong,Koo, Heebeom,Yoon, Hong Yeol,Na, Jin Hee,Choi, Yongseok,Park, Jae Hyung,Lee, Jaeyoung,Han, Moon Hee,Park, Rang&#x2010,Woon,Kim, In&#x2010,San,Jeong, Seo Young,Rh WILEY‐VCH Verlag 2013 Advanced Functional Materials Vol.23 No.44

<P><B>Abstract</B></P><P>With the increasing demand for instant real‐time ultrasound (US) imaging of a specific organ, target‐specific and long‐circulating ultrasound contrast agents are of special interest. A new species of echogenic hyaluronic acid nanoparticles is presented as an ultralong‐acting, liver‐specific, US contrast agent that is distinct from conventional gas‐filled microbubbles. Using an oil‐in‐water (O/W) emulsification method, bioinert and hydrophobic perfluoropentane (PFP) is encapsulated as an ultrasound gas precursor into hyaluronic acid nanoparticles (HANPs) using hydrophobic interactions. HANPs are formulated by self‐assembly, with amphiphilic hyaluronic acid‐5β‐cholanic acid (HA‐CA) conjugating in aqueous conditions. The resulting echogenic PFP‐encapsulated HANPs (Echo‐NPs) show solid nanostructures, differentiated from core‐empty conventional microbubbles, and exhibiting outstanding physical properties as an ultrasound contrast agent. They are more stable and robust echogenic solid bodies with an in vivo favorable hydrodynamic size and because PFPs vaporize gradually, their expansion process is very slow in body conditions. After several systemic circulations, echo‐NPs generated intense and ultralong echo signals for US imaging at the target site. The echogenic properties of Echo‐NPs show a significantly increased half‐life and echo persistence, compared with conventional microbubbles. The results clearly show that echo‐NPs outperform conventional microbubbles in terms of both physical and echogenic in vitro and in vivo properties.</P>

Effects of combined radiofrequency radiation exposure on the cell cycle and its regulatory proteins

Lee, Kwan&#x2010,Yong,Kim, Bong Cho,Han, Na‐,Kyung,Lee, Yun&#x2010,Sil,Kim, Taehong,Yun, Jae&#x2010,Hoon,Kim, Nam,Pack, Jeong&#x2010,Ki,Lee, Jae&#x2010,Seon Wiley Subscription Services, Inc., A Wiley Company 2011 BioElectroMagnetics Vol.32 No.3

<P><B>Abstract</B></P><P>The aim of this study was to investigate whether single or combined radio frequency (RF) radiation exposure has effects on the cell cycle and its regulatory proteins. Exposure of MCF7 cells to either single (837 MHz) or combined (837 and 1950 MHz) RF radiation was conducted at specific absorption rate values of 4 W/kg for 1 h. During the exposure period, the chamber was made isothermal by circulating water through the cavity. After RF radiation exposure, DNA synthesis rate and cell cycle distribution were assessed. The levels of cell cycle regulatory proteins, p53, p21, cyclins, and cyclin‐dependent kinases were also examined. The positive control group was exposed to 0.5 and 4 Gy doses of ionizing radiation (IR) and showed changes in DNA synthesis and cell cycle distribution. The levels of p53, p21, cyclin A, cyclin B1, and cyclin D1 were also affected by IR exposure. In contrast to the IR‐exposed group, neither the single RF radiation‐ nor the combined RF radiation‐exposed group elicited alterations in DNA synthesis, cell cycle distribution, and levels of cell cycle regulatory proteins. These results indicate that neither single nor combined RF radiation affect cell cycle progression. Bioelectromagnetics 32:169–178, 2011. © 2010 Wiley‐Liss, Inc.</P>