University of California, San Diego | Skaggs School of Pharmacy and Pharmaceutical Sciences

Publication List, 2009-2000



Hook, V., Hwang, S.R., Wegrzyn, J., and Bark, S. (2009) Neuropeptides: chemical activity profiling and proteomic approaches. Wiley Encyclopedia of Chemical Biology, pp. 1-12.


Lu, W.D., Asmus, K., Hwang, S.R., Li, S., Woods, V.L., and Hook, V. (2009) Differential accessibilities of dibasic prohormone processing sites of proenkephalin to the aqueous environment revealed by H-D exchange mass spectrometry. Biochemistry 48, 1604-1612.


Bark, S.J., Lu, W.D., and Hook V. (2009) Linear and accurate quantitation of proenkephalin-derived peptides by isotopic labeling with internal standards and mass spectrometry. Anal. Biochem. 389, 18-26.


Hook, V., Funkelstein, L., Toneff, T., Mosier, C., and Hwang, S.R. (2009) Human pituitary contains dual cathepsin L and prohormone convertase processing pathway components involved in converting POMC into the peptide hormones ACTH, alpha-MSH, and beta-endorphin. Endocrine 35, 429-437.


Lee, J.C., and Hook, V. (2009) Proteolytic fragments of chromogranins A and B represent major components of chromaffin granules, illustrated by 2-D proteomics with NH2-terminal Edman peptide sequencing and MALDI-TOF MS. Biochemistry 48, 5254-5262.


Hook, V., Kindy, M., Reinheckel, T., Peters, C., and Hook, G. (2009) Genetic cathepsin B deficiency reduces beta-amyloid in transgenic mice expressing human wild-type amyloid precursor protein. Biochem. Biophys. Res. Commun. 386, 284-288.


Beinfeld, M.C., Funkelstein, L., Foulon, T., Cadel, S., Kitagawa, K., Toneff, T., Reinheckel, T., Peters, C., and Hook, V. (2009) Cathepsin L plays a major role in cholecystokinin production in mouse brain and in pituitary AtT-20 cells: protease gene knockout and inhibitor studies. Peptides. 2009 Jul 7. [Epub ahead of print]


Lortie, M., Bark, S., Blantz, R., and Hook, V. (2009) Detecting low abundance vasoactive peptides in plasma: progress towards absolute quantitation using nano LC/MS. Anal. Biochem. 2009 Jul 15. [Epub ahead of print]




Hook, V., Kindy, M., and Hook, G. (2008) Inhibitors of cathepsin B improve memory and reduce ?-Amyloid in transgenic Alzheimer�s disease mice expressing the wild type, but not the Swedish mutant, ?-secretase site of the amyloid precursor protein. J. Biol. Chem. 283, 7745-7753.


Courel, M., Vasquez, M.S., Hook, V.Y., Mahata, S.K., and Taupenot, L. (2008) Sorting of the neuroendocrine secretory protein secretogranin II into the regulated secretory pathway: role of N- and C-terminal alpha helical domains. J. Biol. Chem. 283, 11807-11822.


Funkelstein, L., Toneff, T., Hwang, S.R., Reinheckel, T., Peters, C., and Hook, V. (2008) Cathepsin L participates in the production of neuropeptide Y in secretory vesicles, demonstrated by protease gene knockout and expression. J. Neurochem. 106, 384-391.


Wegrzyn, J., Drudge, T., Valafar, F., Hook, V. (2008) Bioinformatic analyses of mammalian 5�-UTR sequence properties of mRNAs predicts alternative translation initiation sites. BMC Bioinformatics 9, 232-248.


Hwang, S.R., and Hook, V. (2008) Zinc regulation of aminopeptidase B involved in neuropeptide production. FEBS Lett. 582, 2527-2531.


Hook, V., Toneff, T., Baylon, S., and Sei, C. (2008) Differential activation of enkephalin, galanin, somatostatin, NPY, and VIP neuropeptide production by stimulators of protein kinases A and C in neuroendocrine chromaffin cells. Neuropeptides 42, 503-511.


Hook, V., Schechter, I., Demuth, H.U., Hook, G. (2008) Alternative pathways for production of beta-amyloid peptides of Alzheimer�s disease. Biol. Chem. 389, 1055-1006.


Hwang, S.R., Bundey, R., Toneff, T., and Hook, V. (2008) Endopin serpin protease inhibitors localize with neuropeptides in secretory vesicles and neuroendocrine tissues. Neuroendocrinology 89, 210-216.


Funkelstein, L., Toneff, T., Hwang, S.R., Beuschlein, F., Lichtenauer, U.D., Reinheckel, T., Peters, C., and Hook, V. (2008) Major role of cathepsin L for producing the peptide hormones ACTH, ß-endorphin, and ß-, illustrated by protease gene knockout and expression. J. Biol. Chem. 83, 35652-35659.




Bark, S.J. and Hook, V. (2007) The future of proteomic analysis in biological systems and molecular medicine. Molecular BioSystems 3, 14-17.


Hwang, S.R., O�Neill, A., Bark, S., Foulon, T., and Hook, V. (2007) Secretory vesicle aminopeptidase B related to neuropeptide processing: molecular identification and subcellular localization to enkephalin- and NPY-containing chromaffin granules. J. Neurochem. 100, 1340-1350.


Hwang, S.R., Garza, C., Mosier, C., Toneff, T., Wunderlich, E., Goldsmith, P., and Hook, V. (2007) Cathepsin L expression is directed to secretory vesicles for enkephalin neuropeptide biosynthesis and secretion. J. Biol. Chem. 282, 9556-9563.


Hook, V., Kindy, M., and Hook, G. (2007) Cysteine protease inhibitors effectively reduce in vivo levels of brain beta-amyloid related to Alzheimer�s disease. Biol. Chem. 388, 247-252.


Wegrzyn, J., Lee, J., Neveu, J.M., Lane, W.S., and Hook, V. (2007) Proteomics of neuroendocrine secretory vesicles reveal distinct functional systems for biosynthesis and exocytosis of peptide hormones and neurotransmitters. J. Proteome Research 6, 1652-1665.


Hwang, S.R., and Hook, V.Y. (2007) Multiple domains of endopin 2A for serpin cross-class inhibition of papain. Arch. Biochem. Biophys. 46, 219-224.


O�Connor, D.T., Mahata, S., Mahata, M., Jiang, Q., Hook, V., and Taupenot, L. (2007) Primary culture of bovine chromaffin cells. Nature Protocols 2, 1248-1253.


128. Hook, G., Hook, V.Y., and Kindy, M. (2007) Cysteine protease inhibitors reduce brain beta-amyloid and beta-secrease activity in vivo and are potential Alzheimer�s disease therapeutics. Biol. Chem. 388, 979-983.


Bark, S.J., and Hook, V. (2007) Differential recovery of peptides from sample tubes and the reproducibility of quantitative proteomic data. J. Proteome Research 6, 4511-4516.




Hook, V.Y.H. (2006) Hook, V., Funkelstein, L., Lu, D., Bark, S., Wegrzyn, J., and Hwang, S.R. (2008) Proteases for processing proneuropeptides into peptide neurotransmitters and hormones. Annu. Rev. Pharmacol. Toxicol. 48, 393-423. Biol. Chem. 387, 1429-1439.


Hwang, S-R., Stoka, V., Turk, V., and Hook, V. (2006) Resistance of cathepsin L compared to elastase to proteolysis when complexed with the serpin endopin 2C, and recovery of cathepsin L activity. Biochem. Biophys. Res. Commun. 340, 1238�1243.


Hook, V., Toneff, T., Hook, G., and Reisine, T. (2006) Cysteine proteases as ?-secretases for A� production in the major regulated secretory pathway of neurons: implications for therapeutic strategies in Alzheimer�s disease. In: Oxidative Stress and Age-Related Neurodegeneration, eds. Y. Luo and L. Packer. CRC Press, Boca Raton, FL, pp. 327�342.


Hook, V. (2006) Neuroproteases in peptide neurotransmission and neurodegenerative diseases: applications to drug discovery research. BioDrugs 20, 105�119.


Bundey, R.A.,Hook, V.Y.H. (2006) Protease pathways in peptide neurotransmission and neurodegenerative diseases. Cell. Mol. Neurobiol. 26, 449-469.


Zhang, K., Rao, F., Wen, G., Salem, R., Vaingankar, S., Mahata, M., Mahapatra, N.R., Lillie, E.O., Cadman, P.E., Friese, R.S., Hamilton, B.A., Hook, V.Y., Mahata, S.K., Taupenot, L., and O�Connor, D.T. (2006) Catecholamine storage vesicles and the metabolic syndrome: The role of the chromogranin A fragment pancreastatin. Diabetes Obesity and Metabolism 8, 621�633.


Hook, V.Y.H. (2006) Unique neuronal functions of cathepsin L and cathepsin B in secretory vesicles: biosynthesis of peptides in neurotransmission and neurodegenerative disease. Biol. Chem. 387, 1429�1439.




Hwang, S-R., Garza, C.Z., Wegrzyn, J.L., and Hook, V.Y.H. (2005) Demonstration of GTG as an alternative initiation codon for the serpin endopin 2B-2. Biochem. Biophys. Res. Commun. 327, 837�844.


Hwang, S-R., Stoka, V., Turk, V., and Hook, V.Y.H. (2005) The novel bovine serpin endopin 2C demonstrates selective inhibition of the cysteine protease cathepsin L compared to the serine protease elastase, in cross-class inhibition. Biochemistry 44, 7757�7767.


Hook, V., Toneff, T., Bogyo, M., Greenbaum, D., Medzihradszky, K.F., Neveu, J., Lane, W., Hook, G., and Reisine, T. (2005) Inhibition of cathepsin B reduces ß-amyloid production in regulated secretory vesicles of neuronal chromaffin cells: evidence for cathepsin B as a candidate ß-secretase of Alzheimer�s disease. Biol. Chem. 386, 931�940.




Hook, V.Y.H. (2004) Prohormone thiol protease. In: Handbook of Proteolytic Enzymes, Second Edition. Volume 2. Cysteine, Serine and Threonine Peptidases, eds. A.J. Barrett, N.D. Rawlings, and J.F. Woessner. Academic Press, London, pp. 1408�1413.


Hermel, E., Gafni, J., Propp, S.S., Leavitt, B.R., Wellington, C.L., Young, J.E., Hackam, A.S., Logvinova, A.V., Peel, A.L., Chen, S.F., Hook, V., Singaraja, R., Krajewski, S., Goldsmith, P.C., Ellerby, H.M., Hayden, M.R., Bredesen, D.E., and Ellerby, L.M. (2004) Specific caspase interactions and amplification are involved in selective neuronal vulnerability in Huntington�s disease. Cell Death Differ. 11, 424�438.


Hook, V., Yasothornsrikul, S., Greenbaum, D., Medzihradszky, K.F., Troutner, K., Toneff, T., Bundey, R., Logrinova, A., Reinheckel, T., Peters, C., and Bogyo, M. (2004) Cathepsin L and Arg/Lys aminopeptidase: a distinct prohormone processing pathway for the biosynthesis of peptide neurotransmitters and hormones. Biol. Chem. 385, 473�480.


Hook, V., Lee, J., and Yasothornsrikul, S. (2004) Proteomic studies of the chromaffin granule demonstrates novel proteolytic processing mechanisms for chromogranin A and proenkephalin by secretory vesicle cathepsin L. In: Cell Biology of the Chromaffin Cell, eds. R. Borges and L. Gand�a. University of La Laguna, Spain, pp. 155�160.




Lee, J.C., Taylor, C.V., Gaucher, S.P., Toneff, T., Taupenot, L., Yasothornsrikul, S., Mahata, S.K., Sei, C., Parmer, R.J., Neveu, J.M., Lane, W.S., Gibson, B.W., O�Connor, D.T., and Hook, V.Y.H. (2003) Primary sequence characterization of catestatin intermediates and peptides defines proteolytic cleavage sites utilized for converting chromogranin A into active catestatin secreted from neuroendocrine chromaffin cells. Biochemistry 42, 6938�6946.


Sei, C., Toneff, T., Aaron, W., and Hook, V.Y.H. (2003) Regulation of ACTH levels in anterior pituitary cells during stimulated secretion: evidence for aspartyl and cysteine proteases in the cellular metabolism of ACTH. Peptides 24, 717�725.


Miller, R., Aaron, W., Toneff, T., Vishnuvardhan, D., Beinfeld, M., and Hook, V.Y.H. (2003) Obliteration of ß-melanocyte-stimulating hormone derived from POMC in pituitary and brains of PC2-deficient mice. J. Neurochem. 86, 556�563.


Miller, R., Toneff, T., Vishnuvardhan, D., Beinfeld, M., and Hook, V.Y.H. (2003) Selective roles for the PC2 processing enzyme in the regulation of peptide neurotransmitter levels in brain and peripheral neuroendocrine tissues of PC2 deficient mice. Neuropeptides 37, 140�148.


Yasothornsrikul, S., Greenbaum, D., Medzihradszky, K.F., Toneff, T., Bundey, R., Miller, R., Schilling, B., Petermann, I., Dehnert, J., Logvinova, A., Goldsmith, P., Neveu, J.M., Lane, W.S., Gibson, B., Reinheckel, T., Peters, C., Bogyo, M., and Hook, V. (2003) Cathepsin L in secretory vesicles functions as a prohormone-processing enzyme for production of the enkephalin peptide neurotransmitter. Proc. Natl. Acad. Sci. U S A 100, 9590�9595.


Hook, V.Y.H. and Reisine, T.D. (2003) Cysteine proteases are the major ß-secretase in the regulated secretory pathway that provides most of the ß-amyloid in Alzheimer�s disease: role of BACE 1 in the constitutive secretory pathway. J. Neurosci. Res. 74, 393�405.




Hook, V.Y.H. and Reisine, T.D. (2002) Endorphins. In: Wiley Encyclopedia of Molecular Medicine (Vol. 5), ed. T.E. Creighton. J. Wiley & Sons, Inc., New York, pp. 1161�1164.


Hook, V.Y.H., Toneff, T., Aaron, W., Yasothornsrikul, S., Bundey, R., and Reisine, T. (2002) ß-amyloid peptide in regulated secretory vesicles of chromaffin cells: evidence for multiple cysteine proteolytic activities in distinct pathways for ß-secretase activity in chromaffin vesicles. J. Neurochem. 81, 237�256.


Hook, V. and Metz-Boutigue, M-H. (2002) Protein trafficking to chromaffin granules and proteolytic processing within regulated secretory vesicles of neuroendocrine chromaffin cells. Ann. N.Y. Acad. Sci. 971, 397�405.


Hook, V.Y.H., Yasothornsrikul, S., and Hwang, S-R. (2002) Novel chromaffin granule serpins, endopin 1 and endopin 2: endogenous protease inhibitors with distinct target protease specificities. Ann. N.Y. Acad. Sci. 971, 426�444.


Bundey, R.A., Toneff, T., Pottenger, J., Kennedy, B.P., Ziegler, M.G., and Hook, V.Y.H. (2002) Agonist-stimulated neuropeptide and catecholamine release from bovine adrenal chromaffin cells. Ann. N.Y. Acad. Sci. 971, 338�340.


Hook, V.Y.H. and Hwang, S-R. (2002) Novel secretory vesicle serpins, endopin 1 and endopin 2: endogenous protease inhibitors with distinct target protease specificities. Biol. Chem. 383, 1067�1074.


Sei, C., Toneff, T., Aaron, W., and Hook, V.Y.H. (2002) Regulation of cellular a-MSH and ßendorphin during stimulated secretion from intermediate pituitary cells: involvement of aspartyl and cysteine proteases in the control of cellular levels of a-MSH and ßendorphin. Peptides 23, 1409�1418.


Toneff, T., Mende-Mueller, L., Wu, Y., Hwang, S-R., Bundey, R., Thompson, L.M., Chesselet, M-F., and Hook, V. (2002) Comparison of huntingtin proteolytic fragments in human lymphoblast cell lines and human brain. J. Neurochem. 82, 84�92.


Hwang, S-R., Steineckert, B., Toneff, T., Bundey, R., Logvinova, A.V., Goldsmith, P., and Hook, V.Y.H. (2002) The novel serpin endopin 2 demonstrates cross-class inhibition of papain and elastase: localization of endopin 2 to regulated secretory vesicles of neuroendocrine chromaffin cells. Biochemistry 41, 10397�10405.




Hook, V. (2001) Differential processing of tau in corticobasal degeneration (CBD) and supranuclear palsy (PSP): proteolysis as a central mechanism in neurodegenerative diseases. NeuroReport 12, 27.


Mende-Mueller, L.M., Toneff, T., Hwang, S-R., Chesselet, M-F., and Hook, V.Y.H. (2001) Tissue-specific proteolysis of huntingtin (htt) in human brain: evidence of enhanced levels of N- and C-terminal htt fragments in Huntington�s disease striatum. J. Neurosci. 21, 1830�1837.


Hook, V.Y.H. (2001) Proteolysis of mutant gene products are key mechanisms in neurodegenerative diseases. In: Role of Proteases in the Pathophysiology of Neurodegenerative Disease, eds. N.L. Banik and A.L. Lajtha. Plenum Press, New York, pp. 269�282.


Hook, V.Y.H., Burton, D., Yasothornsrikul, S., Hastings, R.H., and Deftos, L.J. (2001) Proteolysis of proPTHrP(1-141) by �prohormone thiol protease� at multibasic residues generates PTHrP-related peptides: implications of PTHrP peptide production in lung cancer cells. Biochem. Biophys. Res. Commun. 285, 932�938.


Deftos, L.J., Burton, D., Hastings, R.H., Terkeltaub, R., and Hook, V.Y.H. (2001) Comparative tissue distribution of the processing enzymes �prohormone thiol protease,� and prohormone convertases 1 and 2, in human PTHrP-producing cell lines and mammalian neuroendocrine tissues. Endocrine 15, 217�224.




O�Connor, D.T., Insel, P.A., Ziegler, M.G., Hook, V.Y., Smith, D.W., Hamilton, B.A., Taylor, P.W., and Parmer, R.J. (2000) Heredity and the autonomic nervous system in human hypertension. Curr. Hypertens. Rep. 2, 16�22.


Hook, V.Y.H. and Mende-Mueller, L. (2000) Proteolysis in neurodegenerative diseases. In: Contemporary Clinical Neuroscience: Molecular Mechanisms of Neurodegenerative Diseases, ed. M-F. Chesselet, Humana Press, Inc., Totowa, pp. 111�130.


Yasothornsrikul, S. and Hook, V.Y.H. (2000) Detection of proteolytic activity by fluorescent zymogram in-gel assays. BioTechniques 28, 1166�1170.


Taylor, C.V., Taupenot, L., Mahata, S.K., Mahata, M., Wu, H., Yasothornsrikul, S., Toneff, T., Caporale, C., Jiang, Q., Parmer, R.J., Hook, V.Y.H., and O�Connor, D.T. (2000) Formation of the catecholamine release-inhibitory peptide catestatin from chromogranin A. Determination of proteolytic cleavage sites in hormone storage granules. J. Biol. Chem. 275, 22905�22915.


Hwang, S-R., Ng, S-M., Steineckert, B., Seidah, N.G., and Hook, V.Y.H. (2000) Molecular cloning demonstrates structural features of homologous bovine prohormone convertases 1 and 2. DNA Cell Biol. 19, 409�419.


Hwang, S-R., Steineckert, B., and Hook, V.Y.H. (2000) Expression and mutagenesis of the novel serpin endopin 2 demonstrates a requirement for cysteine-374 for dithiothreitol-sensitive inhibition of elastase. Biochemistry 39, 8944�8952.