An Involvement of Oxidative Stress in Endoplasmic Reticulum Stress and Its Associated Diseases

Bhandary, Bidur,Marahatta, Anu,Kim, Hyung-Ryong,Chae, Han-Jung MDPI 2013 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.14 No.1

<P>The endoplasmic reticulum (ER) is the major site of calcium storage and protein folding. It has a unique oxidizing-folding environment due to the predominant disulfide bond formation during the process of protein folding. Alterations in the oxidative environment of the ER and also intra-ER Ca<SUP>2+</SUP> cause the production of ER stress-induced reactive oxygen species (ROS). Protein disulfide isomerases, endoplasmic reticulum oxidoreductin-1, reduced glutathione and mitochondrial electron transport chain proteins also play crucial roles in ER stress-induced production of ROS. In this article, we discuss ER stress-associated ROS and related diseases, and the current understanding of the signaling transduction involved in ER stress.</P>

Mitochondria in relation to cancer metastasis.

Bhandary, Bidur,Marahatta, Anu,Kim, Hyung-Ryong,Chae, Han-Jung Plenum Press 2012 Journal of bioenergetics and biomembranes Vol.44 No.6

<P>Mitochondria, also known as 'Power House of cell,' are crucial organelles, regulating energy metabolism. Recently, an involvement of mitochondria in cancer occurrence and metastasis has been proposed. The roles of mitochondria in cancer progression/metastasis include alteration of glycolysis, regulation of ROS and suppression of intrinsic apoptosis. This mini-review explains the specific mitochondrial characteristics during cancer metastasis with past and recent findings. It may contribute to understanding mitochondria-related mechanisms of cancer metastasis.</P>

The Protective Effect of Rutin against Ischemia/reperfusion-associated Hemodynamic Alteration through Antioxidant Activity

Bidur Bhandary,채한정,Cheng Shi Piao,김도성,이금화,채수완,김형룡 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.6

Reactive oxygen species exert toxic effects during ischemia-reperfusion (I/R) injury of various organs. This study was designed to evaluate the preventive effects of various isoflavonoids such as biochanin A, daidzein, genistein, rutin and quercetin. These compounds are wellknown naturally occurring compounds with beneficial health effects and antioxidant activity. Free radical scavenging activity was measured by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and superoxide dismutase (SOD) assay. Among the isoflavonoids tested, biochanine A, quercetin and rutin showed significant DPPH free radical scavenging activity. Similarly, treatment of biochanine A, genistein and rutin significantly increased SOD activity in neonant rat heart myocyte primary cells as well as in H9C2 cells. For ex vivo study, hearts from Sprague-Dawley rats were perfused in Langendorff apparatus with Krebs-Henseleit solution with a gas mixture of 95% O2 and 5% CO2. Hearts were subjected to 20 min of pre-ischemia followed by 20 min of global ischemia, and then 50 min of reperfusion at 37oC. The test compounds were perfused 10 min before ischemia and during the entire reperfusion period. Among the isoflavonoids tested, only rutin significantly increased left ventricular developed pressure (LVDP) and increased maximum positive and negative dP/dt (+/- dP/dtmax). In left ventricular end diastolic pressure (LVEDP) analysis, rutin, daidzein and biochanin A were effective. Among the isoflavonoids, rutin had consistent protective effects in I/R injury by affecting cardiac dynamic factors as well as by enhancing SOD and DPPH activity.

Characterization of Landslides and Roadside Slope Failures Along the Major Highways in the Midlands of Lesser Himalayan Zone and Across the Siwalik Mountains in Nepal

( Netra P. Bhandary ),( R. Yatabe ),( S. Hasegawa ),( H. Inagaki ),( Hari K. Shrestha ) 대한지질공학회 2007 국제학술발표회 논문집 Vol.2007 No.-

Dentigerous Cyst Associated with Bilaterally Impacted Permanent Mandibular Canines : A Report of a Rare Case

Urvashi Ashwin Shetty,Srikala Bhandary,Audrey Madonna D'Cruz 대한예방치과학회 2014 International Journal of Clinical Preventive Denti Vol.10 No.4

Dentigerous cysts (also known as follicular cysts) are odontogenic cysts of developmental origin associated with the crown of unerupted or partially erupted or impacted teeth. Accumulation of fluid between the reduced enamel epithelium and the tooth crown is suggested as the possible etiopathogenesis of this particular cyst by most authors. However in addition to the developmental origin, few authors have suggested an inflammatory origin to the formation of dentigerous cyst. The dentigerous cysts are commonly associated with impacted canines and third molars. However, bilateral occurrence of the cyst is rare. Here, the authors report a case of dentigerous cyst involving bilaterally impacted mandibular canines in a non-syndromic 12 year old male patient which was surgically enucleated.

Influence of PD 123319 (AT2-Receptor Antagonist) on Catecholamine Secretion in the Perfused Rat Adrenal Medulla

홍순표,Dong-Yoon Lim,Bhandary Bidur,최미성,서영환 대한고혈압학회 2013 Clinical Hypertension Vol.19 No.1

Background: The aim of this study was to examine whether PD 123319 (an angiotensin II type 2 [AT2] receptor antagonist) can influence the release of catecholamines (CA) from the perfused model of the rat adrenal medulla. Methods: The adrenal gland was isolated by the modification of Wakade method, and perfused with normal Krebs-bicarbonate solution. The content of CA was measured using the fluorospectrophotometer. Results: During perfusion of PD 123319 (range, 5 to 50 nM) into an adrenal vein for 90 minutes the CA secretory responses evoked by acetylcholine (ACh), high K+, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), and McN-A-343 was dose- and time-dependently inhibited. Furthermore, loading with PD 123319 for 90minutes also markedly inhibited the CA secretory responses evoked by 4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoro-methyl -phenyl)-pyridine-5-carboxylate (Bay-K-8644), cyclopiazonic acid, veratridine, and angiotensin II (Ang II). PD 123319 did not affect basal CA output. Simultaneous perfusion of PD 123319 and CGP 42112 perfused into an adrenal vein for 90 minutes rather more potently inhibited the CA seretory responses evoked by Ach, high K+, DMPP, Bay-K-8644, veratridine, and Ang II compared to the inhibitory effect by PD123319-treated alone. Conclusions: Taken together, these results show that PD 123319inhibits the CA secretion evoked by both cholinergic and Ang II receptor stimulation from the perfused rat adrenal medulla. This inhibitory effect of PD 123319 seems to be exerted by blocking the influx of both Na+ and Ca2+ through their voltage-dependent channels into the rat adrenomedullary chromaffin cells as well as by reducing the Ca2+ release from its cytoplasmic calcium store, which may be relevant to AT2 receptor blockade. Based on these present data, it is thought that PD 123319 has different activity from previously known AT2 antagonist activity in the perfused adrenal medulla, and that AT2receptors may be involved in the rat adrenomedullary CA secretion.

4-Phenylbutyric acid regulates CCl4-induced acute hepatic dyslipidemia in a mouse model: A mechanism-based PK/PD study

Lee, H.Y.,Marahatta, A.,Bhandary, B.,Kim, H.R.,Chae, H.J. North-Holland ; Elsevier Science Ltd 2016 european journal of pharmacology Vol.777 No.-

<P>Endoplasmic reticulum (ER) stress and associated protein aggregation are closely associated with human diseases, including alterations in hepatic lipid metabolism. Inhibition of ER stress can have a significant effect on the prevention of hepatic dyslipidemia. Here, we studied the role of 4-phenylbutyric acid (4-PBA), a chemical chaperone, on ER stress-induced hepatic lipid accumulation. We studied ER stress induction following CCl4 exposure and delineated mechanisms of the CCl4-induced ER stress response in liver tissue from mice. CCl4 affected the formation of disulfide bonds through excessive hyper-oxidation of protein disulfide isomerase (PDI). Increased complex formation between PDI and its client proteins persisted in CCl4-exposed samples. Conversely, 4-PBA inhibited ER stress via secretion of apolipoprotein B and prevention of hepatic lipid accumulation. We also studied the mechanism-based pharmacokinetic and pharmacodynamic profiles and identified the ER stress-related proteins GRP78 and CHOP, along with plasma apolipoprotein B and triglyceride levels, as novel biomarkers of ER stress-induced hepatic lipid accumulation. ER stress and its clinical relevance for therapeutic approaches were well correlated with the activity of the ER stress regulator 4-PBA, which may be a promising drug candidate for the treatment of hepatic lipid accumulation, such as hepatic steatosis. (C) 2016 The Authors. Published by Elsevier B.V.</P>

PI3Kδ contributes to ER stress-associated asthma through ER-redox disturbances: the involvement of the RIDD–RIG-I–NF-κB axis

김현경,이금화,Kashi Raj Bhattarai,Raghu Patil Junjappa,이화영,Mallikarjun Handigund,Anu Marahatta,Bidur Bhandary,백인환,표재성,김혜경,최옥희,김형룡,이용철,채한정 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

Hyperactivation of phosphoinositol 3-kinase (PI3K) has been suggested to be a potential mechanism for endoplasmic reticulum (ER) stress-enhanced airway hyperresponsiveness, and PI3K inhibitors have been examined as asthma therapeutics. However, the regulatory mechanism linking PI3K to ER stress and related pathological signals in asthma have not been defined. To elucidate these pathogenic pathways, we investigated the influence of a selective PI3Kδ inhibitor, IC87114, on airway inflammation in an ovalbumin/lipopolysaccharide (OVA/LPS)-induced asthma model. In OVA/LPS-induced asthmatic mice, the activity of PI3K, downstream phosphorylation of AKT and activation of nuclear factor-κB (NF-κB) were all significantly elevated; these effects were reversed by IC87114. IC87114 treatment also reduced the OVA/LPS-induced ER stress response by enhancing the intra-ER oxidative folding status through suppression of protein disulfide isomerase activity, ER-associated reactive oxygen species (ROS) accumulation and NOX4 activity. Furthermore, inositol-requiring enzyme-1α (IRE1α)-dependent degradation (RIDD) of IRE1α was reduced by IC87114, resulting in a decreased release of proinflammatory cytokines from bronchial epithelial cells. These results suggest that PI3Kδ may induce severe airway inflammation and hyperresponsiveness by activating NF-κB signaling through ER-associated ROS and RIDD–RIG-I activation. The PI3Kδ inhibitor IC87114 is a potential therapeutic agent against neutrophil-dominant asthma.

Evaluation of Physicochemical Properties, Skin Permeation and Accumulation Profiles of Ketorolac Fatty Ester Prodrugs

Bhandari, Krishna Hari,Newa, Madhuri,Yoon, Sung II,Kim, Jung Sun,Jang, Ki Young,Kim, Jung-Ae,Yoo, Bong Kyo,Woo, Jong Soo,Lee, Jae Hwi,Kim, Dae Duk,Choi, Hang Gon,Yong, Chul Soon Pharmaceutical Society of Japan 2007 BIOLOGICAL & PHARMACEUTICAL BULLETIN Vol.30 No.11

<P>The purpose of this study was to evaluate the physicochemical properties, skin permeation and accumulation profiles of model lipophilic ketorolac fatty ester (esters) prodrugs. Ketorolac linoleate (C18:2), oleate (C18:1) and stearate (C18:0) were evaluated for their solubility, capacity factor, enzymatic hydrolysis, chemical stability, and skin permeation and accumulation profiles using the combination of common permeation enhancing techniques such as the use of supersaturated solution of permeants in the enhancer vehicle, lipophilic receptor solution, enhancer pretreatment of skins, removal of stratum corneum and delipidization of skins <I>etc</I>. Esters were highly lipophilic, chemically stable for the duration of observation, enzymatically unstable in hairless mouse skin/liver homogenates and plasma, and impermeable into the receptor solution. Absence of skin permeation, relative enzymatic stability during permeation and chemical stability of these esters could delineate preliminary possibilities for designing safer topical agents without systemic absorption.</P>

The Contents of Phytosterols, Squalene, and Vitamin E and the Composition of Fatty Acids of Korean Landrace Setaria italica and Sorghum bicolar Seeds

Bhandari, Shiva Ram,Lee, Young-Sang The Plant Resources Society of Korea 2013 한국자원식물학회지 Vol.26 No.6

To characterize the nutraceutical property of Italian millet (Setaria italica) and sorghum (Sorghum bicolor), ten Korean landraces of each crop were collected and their vitamin E (tocopherols and tocotrienols), squalene and phytosterols (campesterol, stigmasterol and ${\beta}$-sitosterol) contents as well as fatty acid composition in seeds were evaluated. Italian millet seeds exhibited 5 forms of vitamin E isomers: three (${\alpha}$-, ${\gamma}$- and ${\delta}$-) tocopherols and two (${\alpha}$- and ${\gamma}$-) tocotrienols, while sorghum seeds showed only three forms of vitamin E isomers: ${\alpha}$- and ${\gamma}$-tocopherol and ${\alpha}$-tocotrienol. In both crops, ${\gamma}$-tocopherol was the major constituent of vitamin E in terms of highest quantity. Total vitamin E content in Italian millet and sorghum landraces were 88.3 mg/kg and 44.3 mg/kg, respectively. Among three phytosterols (campesterol, stigmasterol and ${\beta}$-sitosterol) analyzed, ${\beta}$-sitosterol was the major form comprising about 85% and 65% in Italian millet and sorghum landraces, respectively. Total phytosterols content ranged from 443.0 to 568.5 mg/kg and 442.3 to 719.2 mg/kg in Italian millet and sorghum, respectively. Squalene, a precursor of phytosterols biosynthesis, ranged from 6.8 to 10.2 mg/kg in Italian millet and from 62.2 to 115.2 mg/kg in sorghum. Linoleic, oleic and palmitic acids were the major fatty acids in both of the crops and about 80% of the total fatty acids were unsaturated fatty acids. Among the tested landraces, M09 and S10 showed relatively higher proportion of phytonutrients, suggesting their potential as a gene source for further breeding program.