Protective Effect of Yang Mi Ryung® Extract on Noise-Induced Hearing Loss in Mice

Kim, Min Soo,Kwak, SeongAe,Baek, Heumyoung,Li, Zewu,Choe, Seong-Kyu,Song, Kyung Hindawi 2017 Evidence-based Complementary and Alternative Medic Vol.2017 No.-

<P>Noise-induced hearing loss (NIHL) results from the damage of the delicate hair cells inside the ear after excessive stimulation of noise. Unlike certain lower animals such as amphibians, fishes, and birds, in humans, hair cells cannot be regenerated once they are killed or damaged; thus, there are no therapeutic options to cure NIHL. Therefore, it is more important to protect hair cells from the noise before the damage occurs. In this study, we report the protective effect of Yang Mi Ryung extract (YMRE) against NIHL; this novel therapeutic property of YMRE has not been reported previously. Our data demonstrates that the hearing ability damaged by noise is markedly restored in mice preadministrated with YMRE before noise exposure, to the level of normal control group. Our study also provides the molecular mechanism underlying the protective effect of YMRE against NIHL by showing that YMRE significantly blocks noise-induced apoptotic cell death and reduces reactive oxygen species (ROS) production in cochleae. Moreover, quantitative polymerase chain reaction (qPCR) analysis demonstrates that YMRE has anti-inflammatory properties, suppressing the mRNA levels of TNF<I>α</I> and IL-1<I>β</I> induced by noise exposure. In conclusion, YMRE could be a useful preventive intervention to prevent hearing impairment induced by the exposure to excessive noise.</P>

Autophagy alteration prevents primary cilium disassembly in RPE1 cells

Maharjan, Yunash,Lee, Joon No,Kwak, SeongAe,Lim, Hyewon,Dutta, Raghbendra Kumar,Liu, Zhi-qiang,So, Hong-Seob,Park, Raekil Elsevier 2018 Biochemical and biophysical research communication Vol.500 No.2

<P><B>Abstract</B></P> <P>Primary cilium is a microtubule structure that emanates from the surface of most human cells. Primary cilia assemble during the resting stage (G<SUB>0</SUB> phase) and disassemble with cell cycle progression. Defects associated with the control of the assembly or disassembly of the primary cilium have been implicated in various human diseases, including ciliopathy and cancer. Although studies have suggested the interplay between activation of autophagy and ciliogenesis, any direct mechanism between autophagy abatement and disassembly of primary cilium remains elusive. In this study, we found that the gradual abatement in autophagy during serum-restimulation was a dynamic process and significantly correlated with the disassembly of primary cilium in human retinal pigmented epithelial (RPE1) cells. Although autophagy activity was gradually decreased during serum-restimulation, the alteration in autophagy under the same condition prevented the disassembly of the primary cilium. Autophagy inhibitors such as chloroquine, U18666A and 3-methyladenine (3-MA) retained both the number of ciliated cells and cilium length. In contrast, rapamycin treatment during serum-restimulation maintained the number of ciliated cells with shortened cilia. Taken together, alteration in autophagy during serum-restimulation prevent the disassembly of the primary cilium, and autophagy modulators may serve as useful compounds for studying mechanistic details related to the disassembly of the primary cilium and ciliopathy.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Autophagy abatement and cilia disassembly is correlated during serum-restimulation. </LI> <LI> Both activation and inhibition of autophagy flux during serum-restimulation prevents disassembly of primary cilium. </LI> <LI> Inhibition of autophagy maintains cilium length during serum-restimulation. </LI> <LI> Rapamycin-induced autophagy results in shortened cilium length during serum-restimulation. </LI> </UL> </P>

Ciliogenesis is reciprocally regulated by PPARA and NR1H4/FXR through controlling autophagy in vitro and in vivo

Liu, Zhi-qiang,Lee, Joon No,Son, Myeongjoo,Lim, Jae-Young,Dutta, Raghbendra Kumar,Maharjan, Yunash,Kwak, SeongAe,Oh, Goo Taeg,Byun, Kyunghee,Choe, Seong-Kyu,Park, Raekil Landes Bioscience 2018 AUTOPHAGY Vol.14 No.6

<P>The primary cilia are evolutionarily conserved microtubule-based cellular organelles that perceive metabolic status and thus link the sensory system to cellular signaling pathways. Therefore, ciliogenesis is thought to be tightly linked to autophagy, which is also regulated by nutrient-sensing transcription factors, such as PPARA (peroxisome proliferator activated receptor alpha) and NR1H4/FXR (nuclear receptor subfamily 1, group H, member 4). However, the relationship between these factors and ciliogenesis has not been clearly demonstrated. Here, we present direct evidence for the involvement of macroautophagic/autophagic regulators in controlling ciliogenesis. We showed that activation of PPARA facilitated ciliogenesis independently of cellular nutritional states. Importantly, PPARA-induced ciliogenesis was mediated by controlling autophagy, since either pharmacological or genetic inactivation of autophagy significantly repressed ciliogenesis. Moreover, we showed that pharmacological activator of autophagy, rapamycin, recovered repressed ciliogenesis in ppara(-/-) cells. Conversely, activation of NR1H4 repressed cilia formation, while knockdown of NR1H4 enhanced ciliogenesis by inducing autophagy. The reciprocal activities of PPARA and NR1H4 in regulating ciliogenesis were highlighted in a condition where de-repressed ciliogenesis by NR1H4 knockdown was further enhanced by PPARA activation. The in vivo roles of PPARA and NR1H4 in regulating ciliogenesis were examined in greater detail in ppara(-/-) mice. In response to starvation, ciliogenesis was facilitated in wild-type mice via enhanced autophagy in kidney, while ppara(-/-) mice displayed impaired autophagy and kidney damage resembling ciliopathy. Furthermore, an NR1H4 agonist exacerbated kidney damage associated with starvation in ppara(-/-) mice. These findings indicate a previously unknown role for PPARA and NR1H4 in regulating the autophagy-ciliogenesis axis in vivo.</P>

Fenofibrate exerts protective effects against gentamicin-induced toxicity in cochlear hair cells by activating antioxidant enzymes

Park, Channy,Ji, Hye-Min,Kim, Se-Jin,Kil, Sung-Hee,Lee, Joon No,Kwak, Seongae,Choe, Seong-Kyu,Park, Raekil UNKNOWN 2017 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.39 No.4

<P>Fenofibrate, an activator of peroxisome proliferator-activated receptors (PPARs), has been shown to protect the kidneys and brain cells from oxidative stress; however, its role in preventing hearing loss has not been reported to date, at least to the best of our knowledge. In this study, we demonstrated the protective effects of fenofibrate against gentamicin (GM)-induced ototoxicity. We found that the auditory brainstem response threshold which was increased by GM was significantly reduced by pre-treatment with fenofibrate in rats. In cochlear explants, the disruption of hair cell layers by GM was also markedly attenuated by pre-treatment with fenofibrate. In addition, fenofibrate almost completely abolished GM-induced reactive oxygen species generation, which seemed to be mediated at least in part by the restoration of the expression of PPAR-α-dependent antioxidant enzymes, including catalase and superoxide dismutase (SOD)-1. Of note, fenofibrate markedly increased the expression of heme oxygenase-1 (HO-1) which was also induced to a certain degree by GM alone. The induced expression of HO-1 by fenofibrate appeared to be essential for mediating the protective effects of fenofibrate, as the inhibition of HO-1 activity significantly diminished the protective effects of fenofibrate against the GM-mediated death of sensory hair cells in cochlea explant culture, as well as in zebrafish neuromasts. These results suggest that fenofibrate protects sensory hair cells from GM-induced toxicity by upregulating PPAR-α-dependent antioxidant enzymes, including HO-1. Our results provide insight into the preventive therapy for hearing loss caused by aminoglycoside antibiotics.</P>

Establishment of a bone-specific col10a1:GFP transgenic zebrafish

Kim, Yong-Il,Lee, Suman,Jung, Seung-Hyun,Kim, Hyun-Taek,Choi, Jung-Hwa,Lee, Mi-Sun,You, Kwan-Hee,Yeo, Sang-Yeob,Yoo, Kyeong-Won,Kwak, SeongAe,Lee, Joon No,Park, Raekil,Choe, Seong-Kyu,Kim, Cheol-Hee Springer-Verlag 2013 Molecules and cells Vol.36 No.2

Ambient temperature regulates uncoupling protein 1 expression but fails to induce adipocyte browning in zebrafish

Mao Yousheng,Hong KwangHeum,Bhandari Sushil,Li Li,Liao Weifang,Kim SeongJin,Xiong Yinyi,Nam In-Koo,Choe Seong-Kyu,Kwak SeongAe 경희대학교 융합한의과학연구소 2021 Oriental Pharmacy and Experimental Medicine Vol.21 No.2

Adipocyte browning is a potential strategy to treat obesity. Although uncoupling protein 1 (UCP1) plays an important role in browning and thermogenesis in mammals, it is not known for zebrafish. We found that cold stress, as an efficient way of inducing browning in mammals, failed to induce adipocyte browning in zebrafish, evidenced by the cell morphology and expression of browning genes. Other potential approaches including heat stress and treatment with a chemical known to induce adipocyte browning in mammals also failed to induce browning, suggesting that zebrafish may not be a suitable model to study the browning process. Interestingly however, we found that the liver expresses ucp1 much higher than the adipose tissue in zebrafish. Moreover, the expression of ucp1 in the zebrafish liver is positively regulated by the ambient temperature. These findings suggest that the role of ucp1 in zebrafish may be different from its established role in adipocyte browning in mammals but instead be evolved to adapt to environmental temperature.