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Unsaturated aldehydes generated by free radical\u2010induced lipid peroxidation of polyunsaturated fatty acids, and in particular 4\u2010hydroxy\u2010trans\u20102 nonenal (HNE), are involved in the onset and progression of many pathologies such as cardiovascular (atherosclerosis, long\u2010term complications of diabetes) and neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, and cerebral ischemia). Most of the biological effects of HNE are attributed to the capacity of HNE to react with the nucleophilic sites of proteins and peptides (other than nucleic acids), to form covalently modified biomolecules that can disrupt important cellular functions and induce mutations. By considering the emerging role of HNE in several human diseases, an unequivocal analytical approach as mass spectrometry to detect\/elucidate the structure of protein\u2010HNE adducts in biological matrices is strictly needed not only to understand the reaction mechanism of HNE, but also to gain a deeper insight into the pathological role of HNE. This with the aim to provide intermediate diagnostic biomarkers for human diseases. This review sheds focus on the \u201cstate\u2010of\u2010the\u2010art\u201d of mass spectrometric applications in the field of HNE\u2010protein adducts characterization, starting from the fundamental early studies and discussing the different MS\u2010based approaches that can provide detailed information on the mechanistic aspects of HNE\u2013protein interaction. In the last decade, the increases in the accessible mass ranges of modern instruments and advances in ionization methods have made possible a fundamental improvement in the analysis of protein\u2013HNE adducts by mass spectrometry, and in particular by matrix\u2010assisted laser desorption\/ionization (MALDI) and electrospray ionization (ESI) tandem mass spectrometry. The recent developments and uses of combined analytical approaches to detect and characterize the type\/site of interaction have been highlighted, and several other aspects, including sample preparation methodologies, structure elucidation, and data analysis have also been considered. \u00a9 2004 Wiley Periodicals, Inc., Mass Spec Rev 23:281\u2013305, 2004<\/jats:p>","DOI":"10.1002\/mas.10076","type":"journal-article","created":{"date-parts":[[2004,3,25]],"date-time":"2004-03-25T13:29:41Z","timestamp":1080221381000},"page":"281-305","source":"Crossref","is-referenced-by-count":159,"title":["Mass spectrometry for detection of 4\u2010hydroxy\u2010<i>trans<\/i>\u20102\u2010nonenal (HNE) adducts with peptides and proteins"],"prefix":"10.1002","volume":"23","author":[{"given":"Marina","family":"Carini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giancarlo","family":"Aldini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto Maffei","family":"Facino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,3,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi0271695"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jms.381"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)02545-7"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jms.533"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(80)90209-X"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209493200"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.45.27999"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac9601021"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1006\/taap.1999.8742"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1218(86)90051-0"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.1290080703"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx00046a009"},{"key":"e_1_2_8_14_1","unstructured":"CariniM AldiniG Maffei FacinoR BozzettoL GhirardiniA.2002.Detoxification of cytotoxic unsaturated aldehydes in keratinocytes is a GSH\u2010dependent pathway: Inhibition by UVB and protective effect of histidine and cysteine\u2010containing peptides. 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