Search

Your search keyword '"Gukovskaya, A.S."' showing total 31 results
Start Over Author "Gukovskaya, A.S."
31 results on '"Gukovskaya, A.S."'

1. Mechanisms regulating cytochrome c release in pancreatic mitochondria

Author

Odinokova, I.V., Sung, K.-F., Mareninova, O.A., Hermann, K., Evtodienko, Y., Andreyev, A., Gukovsky, I., and Gukovskaya, A.S.

Subjects
Cytochrome c -- Research, Cytochrome c -- Physiological aspects, Mitochondria -- Research, Mitochondria -- Physiological aspects, Pancreatitis -- Research, Pancreatitis -- Physiological aspects, Pancreatitis -- Development and progression, Health
Published
2009

2. Phosphatidylinositol 3-kinase facilitates bile acid-induced [Ca.sup.2+] responses in pancreatic acinar cells

Author

Fischer, L., Gukovskaya, A.S., Penninger, J.M., Mareninova, O.A., Friess, H., Gukovsky, I., and Pandol, S.J.

Subjects
Bile -- Health aspects, Pancreatic beta cells -- Physiological aspects, Cholecystokinin -- Research, Biological sciences
Abstract

Bile acids are known to induce [Ca.sup.2+] signals in pancreatic acinar cells. We have recently shown that phosphatidylinositol 3-kinase (PI3K) regulates changes in free cytosolic [Ca.sup.2+] concentration ([[[Ca.sup.2+]].sub.i]) elicited by CCK by inhibiting sarco(endo)plasmic reticulum [Ca.sup.2+]-ATPase (SERCA). The present study sought to determine whether PI3K regulates bile acid-induced [[[Ca.sup.2+]].sub.i] responses. In pancreatic acinar cells, pharmacological inhibition of PI3K with LY-294002 or wortmannin inhibited [[[Ca.sup.2+]].sub.i] responses to taurolithocholic acid 3-sulfate (TLC-S) and taurochenodeoxycholate (TCDC). Furthermore, genetic deletion of the PI3K [gamma]-isoform also decreased [[[Ca.sup.2+]].sub.i] responses to bile acids. Depletion of CCK-sensitive intracellular [Ca.sup.2+] pools or application of caffeine inhibited bile acid-induced [[[Ca.sup.2+]].sub.i] signals, indicating that bile acids release [Ca.sup.2+] from agonist-sensitive endoplasmic reticulum (ER) stores via an inositol (1,4,5)-trisphosphate-dependent mechanism. PI3K inhibitors increased the amount of [Ca.sup.2+] in intracellular stores during the exposure of acinar cells to bile acids, suggesting that PI3K negatively regulates SERCA-dependent [Ca.sup.2+] reloading into the ER. Bile acids inhibited [Ca.sup.2+] reloading into ER in permeabilized acinar cells. This effect was augmented by phosphatidylinositol (3,4,5)-trisphosphate ([PIP.sub.3]), suggesting that both bile acids and PI3K act synergistically to inhibit SERCA. Furthermore, inhibition of PI3K by LY-294002 completely inhibited trypsinogen activation caused by the bile acid TLC-S. Our results indicate that PI3K and its product, [PIP.sub.3], facilitate bile acid-induced [[[Ca.sup.2+]].sub.i] responses in pancreatic acinar cells through inhibition of SERCA-dependent [Ca.sup.2+] reloading into the ER and that bile acid-induced trypsinogen activation is mediated by PI3K. The findings have important implications for the mechanism of acute pancreatitis since [[[Ca.sup.2+]].sub.i] increases and trypsinogen activation mediate key pathological processes in this disorder. sarco(endo)plasmic reticulum [Ca.sup.2+]-ATPase; taurolithocholic acid 3-sulfate; taurochenodeoxycholate; cholecystokinin; pancreatitis

Published
2007

3. Phosphatidylinositol 3-kinase regulates [Ca.sup.2+] signaling in pancreatic acinar cells through inhibition of sarco(endo)plasmic reticulum [Ca.sup.2+]-ATPase

Author

Fischer, L., Gukovskaya, A.S., Young, S.H., Gukovsky, I., Lugea, A., Buechler, P., Penninger, J.M., Friess, H., and Pandol, S.J.

Subjects
Pancreas -- Research, Protein kinases -- Research, Biological sciences
Abstract

Calcium is a key mediator of hormone-induced enzyme secretion in pancreatic acinar cells. At the same time, abnormal [Ca.sup.2+] responses are associated with pancreatitis. We have recently shown that inhibition of phosphatidylinositol 3-kinase (P13-kinase) by LY-294002 and wortmannin, as well as genetic deletion of P13-kinase-[gamma], regulates [Ca.sup.2+] responses and the [Ca.sup.2+]-sensitive trypsinogen activation in pancreatic acinar cells. The present study sought to determine the mechanisms of P13-kinase involvement in [Ca.sup.2+] responses induced in these cells by CCK and carbachol. The P13-kinase inhibitors inhibited both [Ca.sup.2+] influx and mobilization from intracellular stores induced by stimulation of acini with physiological and pathological concentrations of CCK, as well as with carbachol. P13-kinase inhibition facilitated the decay of cytosolic free [Ca.sup.2+] concentration ([Ca2+]i) oscillations observed in individual acinar cells. The P13-kinase inhibitors decreased neither CCK-induced inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] production nor Ins(1,4,5)[P.sub.3]-induced [Ca.sup.2+] mobilization, suggesting that the effect of P13-kinase inhibition is not through Ins(1,4,5)[P.sub.3] or Ins(1,4,5)[P.sup.3] receptors. P13-kinase inhibition did not affect [Ca.sup.2+] mobilization induced by thapsigargin, a specific inhibitor of sarco(endo)plasmic reticulum [Ca.sup.2+] -ATPase (SERCA). Moreover, SERCA blockade with thapsigargin abolished the effects of pharmacological and genetic P13-kinase inhibition on [[Ca.sup.2+]]i signals, suggesting SERCA as a downstream target of P13-kinase. Both pharmacological P13-kinase inhibition and genetic deletion of P13-kinase-[gamma] increased the amount of [Ca.sup.2+] in intracellular stores during CCK stimulation. Finally, addition of the P13-kinase product phosphatidylinositol 3,4,5-trisphosphate to permeabilized acini significantly attenuated [Ca.sup.2+] reloading into the endoplasmic reticulum. The results indicate that P13-kinase regulates [Ca.sup.2+] signaling in pancreatic acinar cells through its inhibitory effect on SERCA. pancreas; cholecystokinin; carbachol

Published
2004

4. Guidelines for the use and interpretation of assays for monitoring autophagy

Author

Klionsky, D.J. Abdalla, F.C. Abeliovich, H. Abraham, R.T. Acevedo-Arozena, A. Adeli, K. Agholme, L. Agnello, M. Agostinis, P. Aguirre-Ghiso, J.A. Ahn, H.J. Ait-Mohamed, O. Ait-Si-Ali, S. Akematsu, T. Akira, S. Al-Younes, H.M. Al-Zeer, M.A. Albert, M.L. Albin, R.L. Alegre-Abarrategui, J. Aleo, M.F. Alirezaei, M. Almasan, A. Almonte-Becerril, M. Amano, A. Amaravadi, R. Amarnath, S. Amer, A.O. Andrieu-Abadie, N. Anantharam, V. Ann, D.K. Anoopkumar-Dukie, S. Aoki, H. Apostolova, N. Arancia, G. Aris, J.P. Asanuma, K. Asare, N.Y.O. Ashida, H. Askanas, V. Askew, D.S. Auberger, P. Baba, M. Backues, S.K. Baehrecke, E.H. Bahr, B.A. Bai, X.-Y. Bailly, Y. Baiocchi, R. Baldini, G. Balduini, W. Ballabio, A. Bamber, B.A. Bampton, E.T.W. Bánhegyi, G. Bartholomew, C.R. Bassham, D.C. Bast Jr., R.C. Batoko, H. Bay, B.-H. Beau, I. Béchet, D.M. Begley, T.J. Behl, C. Behrends, C. Bekri, S. Bellaire, B. Bendall, L.J. Benetti, L. Berliocchi, L. Bernardi, H. Bernassola, F. Besteiro, S. Bhatia-Kissova, I. Bi, X. Biard-Piechaczyk, M. Blum, J.S. Boise, L.H. Bonaldo, P. Boone, D.L. Bornhauser, B.C. Bortoluci, K.R. Bossis, I. Bost, F. Bourquin, J.-P. Boya, P. Boyer-Guittaut, M. Bozhkov, P.V. Brady, N.R. Brancolini, C. Brech, A. Brenman, J.E. Brennand, A. Bresnick, E.H. Brest, P. Bridges, D. Bristol, M.L. Brookes, P.S. Brown, E.J. Brumell, J.H. Brunetti-Pierri, N. Brunk, U.T. Bulman, D.E. Bultman, S.J. Bultynck, G. Burbulla, L.F. Bursch, W. Butchar, J.P. Buzgariu, W. Bydlowski, S.P. Cadwell, K. Cahová, M. Cai, D. Cai, J. Cai, Q. Calabretta, B. Calvo-Garrido, J. Camougrand, N. Campanella, M. Campos-Salinas, J. Candi, E. Cao, L. Caplan, A.B. Carding, S.R. Cardoso, S.M. Carew, J.S. Carlin, C.R. Carmignac, V. Carneiro, L.A.M. Carra, S. Caruso, R.A. Casari, G. Casas, C. Castino, R. Cebollero, E. Cecconi, F. Celli, J. Chaachouay, H. Chae, H.-J. Chai, C.-Y. Chan, D.C. Chan, E.Y. Chang, R.C.-C. Che, C.-M. Chen, C.-C. Chen, G.-C. Chen, G.-Q. Chen, M. Chen, Q. Chen, S.S.-L. Chen, W. Chen, X. Chen, X. Chen, X. Chen, Y.-G. Chen, Y. Chen, Y. Chen, Y.-J. Chen, Z. Cheng, A. Cheng, C.H.K. Cheng, Y. Cheong, H. Cheong, J.-H. Cherry, S. Chess-Williams, R. Cheung, Z.H. Chevet, E. Chiang, H.-L. Chiarelli, R. Chiba, T. Chin, L.-S. Chiou, S.-H. Chisari, F.V. Cho, C.H. Cho, D.-H. Choi, A.M.K. Choi, D. Choi, K.S. Choi, M.E. Chouaib, S. Choubey, D. Choubey, V. Chu, C.T. Chuang, T.-H. Chueh, S.-H. Chun, T. Chwae, Y.-J. Chye, M.-L. Ciarcia, R. Ciriolo, M.R. Clague, M.J. Clark, R.S.B. Clarke, P.G.H. Clarke, R. Codogno, P. Coller, H.A. Colombo, M.I. Comincini, S. Condello, M. Condorelli, F. Cookson, M.R. Coombs, G.H. Coppens, I. Corbalan, R. Cossart, P. Costelli, P. Costes, S. Coto-Montes, A. Couve, E. Coxon, F.P. Cregg, J.M. Crespo, J.L. Cronjé, M.J. Cuervo, A.M. Cullen, J.J. Czaja, M.J. D'Amelio, M. Darfeuille-Michaud, A. Davids, L.M. Davies, F.E. De Felici, M. De Groot, J.F. De Haan, C.A.M. De Martino, L. De Milito, A. De Tata, V. Debnath, J. Degterev, A. Dehay, B. Delbridge, L.M.D. Demarchi, F. Deng, Y.Z. Dengjel, J. Dent, P. Denton, D. Deretic, V. Desai, S.D. Devenish, R.J. Di Gioacchino, M. Di Paolo, G. Di Pietro, C. Díaz-Araya, G. Díaz-Laviada, I. Diaz-Meco, M.T. Diaz-Nido, J. Dikic, I. Dinesh-Kumar, S.P. Ding, W.-X. Distelhorst, C.W. Diwan, A. Djavaheri-Mergny, M. Dokudovskaya, S. Dong, Z. Dorsey, F.C. Dosenko, V. Dowling, J.J. Doxsey, S. Dreux, M. Drew, M.E. Duan, Q. Duchosal, M.A. Duff, K. Dugail, I. Durbeej, M. Duszenko, M. Edelstein, C.L. Edinger, A.L. Egea, G. Eichinger, L. Eissa, N.T. Ekmekcioglu, S. El-Deiry, W.S. Elazar, Z. Elgendy, M. Ellerby, L.M. Er Eng, K. Engelbrecht, A.-M. Engelender, S. Erenpreisa, J. Escalante, R. Esclatine, A. Eskelinen, E.-L. Espert, L. Espina, V. Fan, H. Fan, J. Fan, Q.-W. Fan, Z. Fang, S. Fang, Y. Fanto, M. Fanzani, A. Farkas, T. Farré, J.-C. Faure, M. Fechheimer, M. Feng, C.G. Feng, J. Feng, Q. Feng, Y. Fésüs, L. Feuer, R. Figueiredo-Pereira, M.E. Fimia, G.M. Fingar, D.C. Finkbeiner, S. Finkel, T. Finley, K.D. Fiorito, F. Fisher, E.A. Fisher, P.B. Flajolet, M. Florez-McClure, M.L. Florio, S. Fon, E.A. Fornai, F. Fortunato, F. Fotedar, R. Fowler, D.H. Fox, H.S. Franco, R. Frankel, L.B. Fransen, M. Fuentes, J.M. Fueyo, J. Fujii, J. Fujisaki, K. Fujita, E. Fukuda, M. Furukawa, R.H. Gaestel, M. Gailly, P. Gajewska, M. Galliot, B. Galy, V. Ganesh, S. Ganetzky, B. Ganley, I.G. Gao, F.-B. Gao, G.F. Gao, J. Garcia, L. Garcia-Manero, G. Garcia-Marcos, M. Garmyn, M. Gartel, A.L. Gatti, E. Gautel, M. Gawriluk, T.R. Gegg, M.E. Geng, J. Germain, M. Gestwicki, J.E. Gewirtz, D.A. Ghavami, S. Ghosh, P. Giammarioli, A.M. Giatromanolaki, A.N. Gibson, S.B. Gilkerson, R.W. Ginger, M.L. Ginsberg, H.N. Golab, J. Goligorsky, M.S. Golstein, P. Gomez-Manzano, C. Goncu, E. Gongora, C. Gonzalez, C.D. Gonzalez, R. González-Estévez, C. González-Polo, R.A. Gonzalez-Rey, E. Gorbunov, N.V. Gorski, S. Goruppi, S. Gottlieb, R.A. Gozuacik, D. Granato, G.E. Grant, G.D. Green, K.N. Gregorc, A. Gros, F. Grose, C. Grunt, T.W. Gual, P. Guan, J.-L. Guan, K.-L. Guichard, S.M. Gukovskaya, A.S. Gukovsky, I. Gunst, J. Gustafsson, A.B. Halayko, A.J. Hale, A.N. Halonen, S.K. Hamasaki, M. Han, F. Han, T. Hancock, M.K. Hansen, M. Harada, H. Harada, M. Hardt, S.E. Harper, J.W. Harris, A.L. Harris, J. Harris, S.D. Hashimoto, M. Haspel, J.A. Hayashi, S.-I. Hazelhurst, L.A. He, C. He, Y.-W. Hébert, M.-J. Heidenreich, K.A. Helfrich, M.H. Helgason, G.V. Henske, E.P. Herman, B. Herman, P.K. Hetz, C. Hilfiker, S. Hill, J.A. Hocking, L.J. Hofman, P. Hofmann, T.G. Höhfeld, J. Holyoake, T.L. Hong, M.-H. Hood, D.A. Hotamisligil, G.S. Houwerzijl, E.J. Høyer-Hansen, M. Hu, B. Hu, C.-A.A. Hu, H.-M. Hua, Y. Huang, C. Huang, J. Huang, S. Huang, W.-P. Huber, T.B. Huh, W.-K. Hung, T.-H. Hupp, T.R. Hur, G.M. Hurley, J.B. Hussain, S.N.A. Hussey, P.J. Hwang, J.J. Hwang, S. Ichihara, A. Ilkhanizadeh, S. Inoki, K. Into, T. Iovane, V. Iovanna, J.L. Ip, N.Y. Isaka, Y. Ishida, H. Isidoro, C. Isobe, K.-I. Iwasaki, A. Izquierdo, M. Izumi, Y. Jaakkola, P.M. Jäättelä, M. Jackson, G.R. Jackson, W.T. Janji, B. Jendrach, M. Jeon, J.-H. Jeung, E.-B. Jiang, H. Jiang, H. Jiang, J.X. Jiang, M. Jiang, Q. Jiang, X. Jiménez, A. Jin, M. Jin, S. Joe, C.O. Johansen, T. Johnson, D.E. Johnson, G.V.W. Jones, N.L. Joseph, B. Joseph, S.K. Joubert, A.M. Juhász, G. Juillerat-Jeanneret, L. Jung, C.H. Jung, Y.-K. Kaarniranta, K. Kaasik, A. Kabuta, T. Kadowaki, M. Kagedal, K. Kamada, Y. Kaminskyy, V.O. Kampinga, H.H. Kanamori, H. Kang, C. Kang, K.B. Il Kang, K. Kang, R. Kang, Y.-A. Kanki, T. Kanneganti, T.-D. Kanno, H. Kanthasamy, A.G. Kanthasamy, A. Karantza, V. Kaushal, G.P. Kaushik, S. Kawazoe, Y. Ke, P.-Y. Kehrl, J.H. Kelekar, A. Kerkhoff, C. Kessel, D.H. Khalil, H. Kiel, J.A.K.W. Kiger, A.A. Kihara, A. Kim, D.R. Kim, D.-H. Kim, D.-H. Kim, E.-K. Kim, H.-R. Kim, J.-S. Kim, J.H. Kim, J.C. Kim, J.K. Kim, P.K. Kim, S.W. Kim, Y.-S. Kim, Y. Kimchi, A. Kimmelman, A.C. King, J.S. Kinsella, T.J. Kirkin, V. Kirshenbaum, L.A. Kitamoto, K. Kitazato, K. Klein, L. Klimecki, W.T. Klucken, J. Knecht, E. Ko, B.C.B. Koch, J.C. Koga, H. Koh, J.-Y. Koh, Y.H. Koike, M. Komatsu, M. Kominami, E. Kong, H.J. Kong, W.-J. Korolchuk, V.I. Kotake, Y. Koukourakis, M.I. Kouri Flores, J.B. Kovács, A.L. Kraft, C. Krainc, D. Krämer, H. Kretz-Remy, C. Krichevsky, A.M. Kroemer, G. Krüger, R. Krut, O. Ktistakis, N.T. Kuan, C.-Y. Kucharczyk, R. Kumar, A. Kumar, R. Kumar, S. Kundu, M. Kung, H.-J. Kurz, T. Kwon, H.J. La Spada, A.R. Lafont, F. Lamark, T. Landry, J. Lane, J.D. Lapaquette, P. Laporte, J.F. László, L. Lavandero, S. Lavoie, J.N. Layfield, R. Lazo, P.A. Le, W. Le Cam, L. Ledbetter, D.J. Lee, A.J.X. Lee, B.-W. Lee, G.M. Lee, J. Lee, J.-H. Lee, M. Lee, M.-S. Lee, S.H. Leeuwenburgh, C. Legembre, P. Legouis, R. Lehmann, M. Lei, H.-Y. Lei, Q.-Y. Leib, D.A. Leiro, J. Lemasters, J.J. Lemoine, A. Lesniak, M.S. Lev, D. Levenson, V.V. Levine, B. Levy, E. Li, F. Li, J.-L. Li, L. Li, S. Li, W. Li, X.-J. Li, Y.-B. Li, Y.-P. Liang, C. Liang, Q. Liao, Y.-F. Liberski, P.P. Lieberman, A. Lim, H.J. Lim, K.-L. Lim, K. Lin, C.-F. Lin, F.-C. Lin, J. Lin, J.D. Lin, K. Lin, W.-W. Lin, W.-C. Lin, Y.-L. Linden, R. Lingor, P. Lippincott-Schwartz, J. Lisanti, M.P. Liton, P.B. Liu, B. Liu, C.-F. Liu, K. Liu, L. Liu, Q.A. Liu, W. Liu, Y.-C. Liu, Y. Lockshin, R.A. Lok, C.-N. Lonial, S. Loos, B. Lopez-Berestein, G. López-Otín, C. Lossi, L. Lotze, M.T. Lõw, P. Lu, B. Lu, B. Lu, B. Lu, Z. Luciano, F. Lukacs, N.W. Lund, A.H. Lynch-Day, M.A. Ma, Y. Macian, F. MacKeigan, J.P. Macleod, K.F. Madeo, F. Maiuri, L. Maiuri, M.C. Malagoli, D. Malicdan, M.C.V. Malorni, W. Man, N. Mandelkow, E.-M. Manon, S. Manov, I. Mao, K. Mao, X. Mao, Z. Marambaud, P. Marazziti, D. Marcel, Y.L. Marchbank, K. Marchetti, P. Marciniak, S.J. Marcondes, M. Mardi, M. Marfe, G. Mariño, G. Markaki, M. Marten, M.R. Martin, S.J. Martinand-Mari, C. Martinet, W. Martinez-Vicente, M. Masini, M. Matarrese, P. Matsuo, S. Matteoni, R. Mayer, A. Mazure, N.M. McConkey, D.J. McConnell, M.J. McDermott, C. McDonald, C. McInerney, G.M. McKenna, S.L. McLaughlin, B. McLean, P.J. McMaster, C.R. McQuibban, G.A. Meijer, A.J. Meisler, M.H. Meléndez, A. Melia, T.J. Melino, G. Mena, M.A. Menendez, J.A. Menna-Barreto, R.F.S. Menon, M.B. Menzies, F.M. Mercer, C.A. Merighi, A. Merry, D.E. Meschini, S. Meyer, C.G. Meyer, T.F. Miao, C.-Y. Miao, J.-Y. Michels, P.A.M. Michiels, C. Mijaljica, D. Milojkovic, A. Minucci, S. Miracco, C. Miranti, C.K. Mitroulis, I. Miyazawa, K. Mizushima, N. Mograbi, B. Mohseni, S. Molero, X. Mollereau, B. Mollinedo, F. Momoi, T. Monastyrska, I. Monick, M.M. Monteiro, M.J. Moore, M.N. Mora, R. Moreau, K. Moreira, P.I. Moriyasu, Y. Moscat, J. Mostowy, S. Mottram, J.C. Motyl, T. Moussa, C.E.-H. Müller, S. Muller, S. Münger, K. Münz, C. Murphy, L.O. Murphy, M.E. Musarò, A. Mysorekar, I. Nagata, E. Nagata, K. Nahimana, A. Nair, U. Nakagawa, T. Nakahira, K. Nakano, H. Nakatogawa, H. Nanjundan, M. Naqvi, N.I. Narendra, D.P. Narita, M. Navarro, M. Nawrocki, S.T. Nazarko, T.Y. Nemchenko, A. Netea, M.G. Neufeld, T.P. Ney, P.A. Nezis, I.P. Nguyen, H.P. Nie, D. Nishino, I. Nislow, C. Nixon, R.A. Noda, T. Noegel, A.A. Nogalska, A. Noguchi, S. Notterpek, L. Novak, I. Nozaki, T. Nukina, N. Nürnberger, T. Nyfeler, B. Obara, K. Oberley, T.D. Oddo, S. Ogawa, M. Ohashi, T. Okamoto, K. Oleinick, N.L. Oliver, F.J. Olsen, L.J. Olsson, S. Opota, O. Osborne, T.F. Ostrander, G.K. Otsu, K. Ou, J.-H.J. Ouimet, M. Overholtzer, M. Ozpolat, B. Paganetti, P. Pagnini, U. Pallet, N. Palmer, G.E. Palumbo, C. Pan, T. Panaretakis, T. Pandey, U.B. Papackova, Z. Papassideri, I. Paris, I. Park, J. Park, O.K. Parys, J.B. Parzych, K.R. Patschan, S. Patterson, C. Pattingre, S. Pawelek, J.M. Peng, J. Perlmutter, D.H. Perrotta, I. Perry, G. Pervaiz, S. Peter, M. Peters, G.J. Petersen, M. Petrovski, G. Phang, J.M. Piacentini, M. Pierre, P. Pierrefite-Carle, V. Pierron, G. Pinkas-Kramarski, R. Piras, A. Piri, N. Platanias, L.C. Pöggeler, S. Poirot, M. Poletti, A. Poüs, C. Pozuelo-Rubio, M. Prætorius-Ibba, M. Prasad, A. Prescott, M. Priault, M. Produit-Zengaffinen, N. Progulske-Fox, A. Proikas-Cezanne, T. Przedborski, S. Przyklenk, K. Puertollano, R. Puyal, J. Qian, S.-B. Qin, L. Qin, Z.-H. Quaggin, S.E. Raben, N. Rabinowich, H. Rabkin, S.W. Rahman, I. Rami, A. Ramm, G. Randall, G. Randow, F. Rao, V.A. Rathmell, J.C. Ravikumar, B. Ray, S.K. Reed, B.H. Reed, J.C. Reggiori, F. Régnier-Vigouroux, A. Reichert, A.S. Reiners Jr., J.J. Reiter, R.J. Ren, J. Revuelta, J.L. Rhodes, C.J. Ritis, K. Rizzo, E. Robbins, J. Roberge, M. Roca, H. Roccheri, M.C. Rocchi, S. Rodemann, H.P. De Córdoba, S.R. Rohrer, B. Roninson, I.B. Rosen, K. Rost-Roszkowska, M.M. Rouis, M. Rouschop, K.M.A. Rovetta, F. Rubin, B.P. Rubinsztein, D.C. Ruckdeschel, K. Rucker III, E.B. Rudich, A. Rudolf, E. Ruiz-Opazo, N. Russo, R. Rusten, T.E. Ryan, K.M. Ryter, S.W. Sabatini, D.M. Sadoshima, J. Saha, T. Saitoh, T. Sakagami, H. Sakai, Y. Salekdeh, G.H. Salomoni, P. Salvaterra, P.M. Salvesen, G. Salvioli, R. Sanchez, A.M.J. Sánchez-Alcázar, J.A. Sánchez-Prieto, R. Sandri, M. Sankar, U. Sansanwal, P. Santambrogio, L. Saran, S. Sarkar, S. Sarwal, M. Sasakawa, C. Sasnauskiene, A. Sass, M. Sato, K. Sato, M. Schapira, A.H.V. Scharl, M. Schätzl, H.M. Scheper, W. Schiaffino, S. Schneider, C. Schneider, M.E. Schneider-Stock, R. Schoenlein, P.V. Schorderet, D.F. Schüller, C. Schwartz, G.K. Scorrano, L. Sealy, L. Seglen, P.O. Segura-Aguilar, J. Seiliez, I. Seleverstov, O. Sell, C. Seo, J.B. Separovic, D. Setaluri, V. Setoguchi, T. Settembre, C. Shacka, J.J. Shanmugam, M. Shapiro, I.M. Shaulian, E. Shaw, R.J. Shelhamer, J.H. Shen, H.-M. Shen, W.-C. Sheng, Z.-H. Shi, Y. Shibuya, K. Shidoji, Y. Shieh, J.-J. Shih, C.-M. Shimada, Y. Shimizu, S. Shintani, T. Shirihai, O.S. Shore, G.C. Sibirny, A.A. Sidhu, S.B. Sikorska, B. Silva-Zacarin, E.C.M. Simmons, A. Simon, A.K. Simon, H.-U. Simone, C. Simonsen, A. Sinclair, D.A. Singh, R. Sinha, D. Sinicrope, F.A. Sirko, A. Siu, P.M. Sivridis, E. Skop, V. Skulachev, V.P. Slack, R.S. Smaili, S.S. Smith, D.R. Soengas, M.S. Soldati, T. Song, X. Sood, A.K. Soong, T.W. Sotgia, F. Spector, S.A. Spies, C.D. Springer, W. Srinivasula, S.M. Stefanis, L. Steffan, J.S. Stendel, R. Stenmark, H. Stephanou, A. Stern, S.T. Sternberg, C. Stork, B. Strålfors, P. Subauste, C.S. Sui, X. Sulzer, D. Sun, J. Sun, S.-Y. Sun, Z.-J. Sung, J.J.Y. Suzuki, K. Suzuki, T. Swanson, M.S. Swanton, C. Sweeney, S.T. Sy, L.-K. Szabadkai, G. Tabas, I. Taegtmeyer, H. Tafani, M. Takács-Vellai, K. Takano, Y. Takegawa, K. Takemura, G. Takeshita, F. Talbot, N.J. Tan, K.S.W. Tanaka, K. Tanaka, K. Tang, D. Tang, D. Tanida, I. Tannous, B.A. Tavernarakis, N. Taylor, G.S. Taylor, G.A. Taylor, J.P. Terada, A.S. Terman, A. Tettamanti, G. Thevissen, K. Thompson, C.B. Thorburn, A. Thumm, M. Tian, F. Tian, Y. Tocchini-Valentini, G. Tolkovsky, A.M. Tomino, Y. Tönges, L. Tooze, S.A. Tournier, C. Tower, J. Towns, R. Trajkovic, V. Travassos, L.H. Tsai, T.-F. Tschan, M.P. Tsubata, T. Tsung, A. Turk, B. Turner, L.S. Tyagi, S.C. Uchiyama, Y. Ueno, T. Umekawa, M. Umemiya-Shirafuji, R. Unni, V.K. Vaccaro, M.I. Valente, E.M. Van Den Berghe, G. Van Der Klei, I.J. Van Doorn, W.G. Van Dyk, L.F. Van Egmond, M. Van Grunsven, L.A. Vandenabeele, P. Vandenberghe, W.P. Vanhorebeek, I. Vaquero, E.C. Velasco, G. Vellai, T. Vicencio, J.M. Vierstra, R.D. Vila, M. Vindis, C. Viola, G. Viscomi, M.T. Voitsekhovskaja, O.V. Von Haefen, C. Votruba, M. Wada, K. Wade-Martins, R. Walker, C.L. Walsh, C.M. Walter, J. Wan, X.-B. Wang, A. Wang, C. Wang, D. Wang, F. Wang, F. Wang, G. Wang, H. Wang, H.-G. Wang, H.-D. Wang, J. Wang, K. Wang, M. Wang, R.C. Wang, X. Wang, X. Wang, Y.-J. Wang, Y. Wang, Z. Wang, Z.C. Wang, Z. Wansink, D.G. Ward, D.M. Watada, H. Waters, S.L. Webster, P. Wei, L. Weihl, C.C. Weiss, W.A. Welford, S.M. Wen, L.-P. Whitehouse, C.A. Whitton, J.L. Whitworth, A.J. Wileman, T. Wiley, J.W. Wilkinson, S. Willbold, D. Williams, R.L. Williamson, P.R. Wouters, B.G. Wu, C. Wu, D.-C. Wu, W.K.K. Wyttenbach, A. Xavier, R.J. Xi, Z. Xia, P. Xiao, G. Xie, Z. Xie, Z. Xu, D.-Z. Xu, J. Xu, L. Xu, X. Yamamoto, A. Yamamoto, A. Yamashina, S. Yamashita, M. Yan, X. Yanagida, M. Yang, D.-S. Yang, E. Yang, J.-M. Yang, S.Y. Yang, W. Yang, W.Y. Yang, Z. Yao, M.-C. Yao, T.-P. Yeganeh, B. Yen, W.-L. Yin, J.-J. Yin, X.-M. Yoo, O.-J. Yoon, G. Yoon, S.-Y. Yorimitsu, T. Yoshikawa, Y. Yoshimori, T. Yoshimoto, K. You, H.J. Youle, R.J. Younes, A. Yu, L. Yu, L. Yu, S.-W. Yu, W.H. Yuan, Z.-M. Yue, Z. Yun, C.-H. Yuzaki, M. Zabirnyk, O. Silva-Zacarin, E. David Zacks, E. Zacksenhaus, L. Zaffaroni, N. Zakeri, Z. Zeh III, H.J. Zeitlin, S.O. Zhang, H. Zhang, H.-L. Zhang, J. Zhang, J.-P. Zhang, L. Zhang, L. Zhang, M.-Y. Zhang, X.D. Zhao, M. Zhao, Y.-F. Zhao, Y. Zhao, Z.J. Zheng, X. Zhivotovsky, B. Zhong, Q. Zhou, C.-Z. Zhu, C. Zhu, W.-G. Zhu, X.-F. Zhu, X. Zhu, Y. Zoladek, T. Zong, W.-X. Zorzano, A. Zschocke, J. Zuckerbraun, B.

Abstract

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field. © 2012 Landes Bioscience.

Published
2012

5. Rab disordering in pancreatitis

Author

Mareninova, O.A., primary, Yakubov, I., additional, Yuan, J., additional, Lugea, A., additional, Gukovsky, I., additional, and Gukovskaya, A.S., additional

Published
2013
Full Text
View/download PDF

22. Phosphatidylinositide 3-kinase @c regulates key pathologic responses to cholecystokinin in pancreatic acinar cells

Author

Gukovsky, I., Cheng, J.H., Nam, K.J., Lee, O.T., Lugea, A., Fischer, L., Penninger, J.M., Pandol, S.J., and Gukovskaya, A.S.

Abstract

Background & Aims: Early events in the pancreatic acinar cell critical for development of pancreatitis include activation of the transcription factor nuclear factor @kB (NF-@kB), abnormal Ca^2^+ responses, and trypsinogen activation. Mechanisms underlying these responses, which can be studied in isolated pancreatic acini stimulated with supraphysiologic doses of cholecystokinin (CCK-8), remain poorly understood. We here report that these responses are regulated by phosphatidylinositide 3-kinase (PI3K) @c. Methods: To inactivate PI3K, we used mice deficient in the catalytic PI3K@c subunit p110@c as well as the PI3K inhibitors LY294002 and wortmannin. We measured Ca^2^+ responses by using Fura-2, NF-@kB-binding activity by electromobility shift assay, I@kB degradation by Western blotting, and trypsinogen activation by fluorogenic assay. Results: CCK-induced intracellular Ca^2^+ mobilization, Ca^2^+ influx, trypsinogen, and NF-@kB activation were all diminished in pancreatic acini isolated from p110@c^-^/^- mice. Both in mouse and rat acini, these responses were inhibited by the PI3K inhibitors. The Ca^2^+ signal and trypsinogen activation were similarly reduced in acini isolated from p110@c^-^/^- and p110@c^+^/^- mice compared with wild-type mice. By contrast, NF-@kB activation was inhibited in p110@c^-^/^- acini but not in p110@c^+^/^- acini. These differences indicate that the mechanism of NF-@kB regulation by PI3K@c differs from those for the Ca^2^+ and trypsinogen responses. CCK-induced responses in p110@c^-^/^- acini were all further inhibited by LY294002, indicating the involvement of other PI3K isoform(s), in addition to PI3K@c. Conclusions: The results show that key pathologic responses of the pancreatic acinar cell are regulated by PI3K@c and suggest an important role for this PI3K isoform in pancreatitis.

Published
2004
Full Text
View/download PDF

23. Nonoxidative ethanol metabolites alter extracellular matrix protein content in rat pancreas

Author

Lugea, A., Gukovsky, I., Gukovskaya, A.S., and Pandol, S.J.

Abstract

Background & aims: The mechanisms involved in ethanol-induced pancreas fibrosis are poorly understood. Here we show that fatty acid ethyl esters (FAEEs), nonoxidative ethanol metabolites, increase extracellular matrix (ECM) protein levels in pancreas. Methods: Rat pancreatic acini were incubated for 1-4 hours with FAEEs or acetaldehyde. In another set of experiments, rats received an intravenous infusion of FAEEs for 6 hours. Collagens were assessed by a hydroxyproline assay. Laminin and fibronectin were analyzed by Western blotting. Gene expression of ECM proteins was measured by conventional and real-time reverse-transcription polymerase chain reaction (RT-PCR). Matrix metalloproteinase (MMP), plasmin, and urokinase-type plasminogen activator (uPA) activities were determined by zymography and fluorogenic assays. Results: FAEEs increased collagen, laminin, and fibronectin levels in pancreatic acini without affecting messenger RNA (mRNA) expression for these proteins. Actinomycin D, a transcriptional inhibitor, did not block the increase in ECM proteins induced by FAEEs. FAEEs reduced the activity of the serine protease, plasmin, and that of the uPA. Consistent with these results, the serine protease inhibitor aprotinin reproduced the effects of FAEEs and prevented the further increase in ECM proteins induced by FAEEs. In vivo administration of FAEEs reduced plasmin and uPA activities and increased ECM protein levels in pancreas. Acetaldehyde had minor effects on ECM protein levels and did not affect plasmin activity. Conclusions: FAEEs increase ECM protein levels in pancreas. The results suggest that this effect is caused primarily by an inhibition in ECM degradation via serine proteases including the plasminogen system.

Published
2003
Full Text
View/download PDF

24. Neutrophils and NADPH oxidase mediate intrapancreatic trypsin activation in murine experimental acute pancreatitis

Author

Gukovskaya, A.S., Vaquero, E., Zaninovic, V., Gorelick, F.S., Lusis, A.J., Brennan, M.L., Holland, S., and Pandol, S.J.

Abstract

Background & Aims:: Intrapancreatic activation of digestive enzymes is a key event in the parenchymal cell injury of pancreatitis. We hypothesized that neutrophils recruited to the pancreas during pancreatitis may contribute to such activation. Methods:: To cause experimental pancreatitis, rats and mice were treated with high doses of cerulein. Activation of the digestive enzyme, trypsin, was measured in pancreatic homogenates using a fluorogenic assay and localized immunocytochemically with antibody to trypsin-activation peptide (TAP). Results:: Compared with controls, rats depleted of neutrophils with antineutrophil serum exhibited a marked attenuation in intrapancreatic trypsin activation and acinar cell TAP labeling induced by high-dose cerulein. To examine the mechanism, mice deficient in either nicontinamide adenine dinucleotide phosphate (NADPH) oxidase, or myeloperoxidase (MPO) were studied for trypsin activation. Mice deficient in NADPH oxidase exhibited attenuation of the cerulein-induced trypsin activation, but those deficient in MPO did not. Using measurements of Western blot analysis, generation of reactive oxygen species, and immunocytochemistry, we demonstrated the NADPH oxidase activity is in neutrophils and not pancreatic acinar tissue. Conclusions:: The results demonstrate a novel role for neutrophils infiltrating the pancreas in pathologic activation of digestive enzymes in acute pancreatitis and indicate that this effect is mediated by products of NADPH oxidase.

Published
2002
Full Text
View/download PDF

25. Ethanol metabolism and transcription factor activation in pancreatic acinar cells in rats

Author

Gukovskaya, A.S., Mouria, M., Gukovsky, I., Reyes, C.N., Kasho, V.N., Faller, L.D., and Pandol, S.J.

Abstract

Background & Aims:: Ethanol metabolism by pancreatic acinar cells and the role of its metabolites in ethanol toxicity to the pancreas remain largely unknown. Here, we characterize ethanol metabolism in pancreatic acinar cells and determine the effects of ethanol metabolites on nuclear factor @kB (NF-@kB) and activator protein (AP)-1, transcription factors that are activated in pancreatitis and mediate expression of inflammatory molecules critical for this disease. Methods:: We measured activities of fatty acid ethyl ester (FAEE) synthase and alcohol dehydrogenase (ADH), as well as accumulation of ethanol metabolites. We measured the effects of ethanol and its metabolites on NF-@kB and AP-1 activation by using a gel shift assay. Results: Pancreas metabolizes ethanol via both oxidative and nonoxidative pathways. Acinar cells are the main source of ethanol metabolism in the pancreas. Compared with the liver, FAEE synthase activity in the pancreas is greater, whereas that of ADH is much less. FAEEs activated NF-@kB and AP-1, whereas acetaldehyde inhibited NF-@kB activation. Ethanol decreased NF-@kB binding activity in acinar cells, which was potentiated by cyanamide. Conclusion:: Oxidative and nonoxidative ethanol metabolites regulate transcription factors differently in pancreatic acinar cells. Ethanol may regulate NF-@kB and AP-1 positively or negatively, depending on which metabolic pathway's effect predominates. These regulatory mechanisms may play a role in ethanol toxicity to the pancreas.

Published
2002
Full Text
View/download PDF

26. Ethanol diet increases the sensitivity of rats to pancreatitis induced by cholecystokinin octapeptide

Author

Pandol, S.J., Periskic, S., Gukovsky, I., Zaninovic, V., Jung, Y., Zong, Y., Solomon, T.E., Gukovskaya, A.S., and Tsukamoto, H.

Abstract

Background & Aims: Although alcoholism is a major cause of pancreatitis, the pathogenesis of this disorder remains obscure. Failure to produce experimental alcoholic pancreatitis suggests that ethanol may only increase predisposition to pancreatitis. This study sought to develop a model of ethanol pancreatitis by determining if an ethanol diet sensitizes rats to pancreatitis caused by cholecystokinin octapeptide (CCK-8). Methods: Rats were fed intragastrically either control or ethanol diet for 2 or 6 weeks. The animals were then infused for 6 hours with either saline or CCK-8 at a dose of 3000 pmol . kg^-^1 . h^-^1, which by itself did not induce pancreatitis. The following parameters were measured: serum amylase and lipase levels, pancreatic weight, inflammatory infiltration, number of apoptotic acinar cells, pancreatic messenger RNA (mRNA) expression of cytokines and chemokines, and nuclear factor (NF)-@kB activity. Results: All measures of pancreatitis, as well as NF-@kB activity and mRNA expression for tumor necrosis factor @a, interleukin 6, monocyte chemotactic protein 1, macrophage inflammatory protein 2, and inducible nitric oxide synthase, were significantly increased only in rats treated with ethanol plus CCK-8. Conclusions: An ethanol diet sensitizes rats to pancreatitis caused by CCK-8. The combined action of ethanol and CCK-8 results in NF-@kB activation and up-regulation of proinflammatory cytokines and chemokines in the pancreas. These mechanisms may contribute to the development of alcoholic pancreatitis. GASTROENTEROLOGY 1999;117:706-716

Published
1999
Full Text
View/download PDF

27. Inhibitors of arachidonic acid metabolism eliminate the increase in cytosolic free calcium induced by the mitogen concanavalin A in rat thymocytes

Author

Gukovskaya, A.S., Pulido, H.Arias, Zinchenko, V.P., and Evtodienko, Yu.V.

Abstract

Using inhibitors of arachidonic acid (AA) metabolism, the possible involvement of AA products in the generation of [Ca2+]iand the pHirise induced by the mitogen concanavalin A (Con A) in rat thymocytes has been studied. The lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA, 10 μM) and the phospholipase A2inhibitor bromophenacyl bromide (10 μM) eliminated the [Ca2+]isignal induced by Con A; the cyclooxygenase blocker indomethacin also inhibited it. However, neither NDGA nor indomethacin suppressed the pHirise stimulated by Con A. Exogenous AA induced an increase in [Ca2+]ibut not in the pHi. These results indicate that AA metabolites, probably of the lipoxygenase pathway, take part in the generation of the [Ca2+]iresponse to the mitogen. In contrast, they appear not to be involved in the pHirise evoked by Con A.

Published
1989
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results