{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T20:27:19Z","timestamp":1786739239385,"version":"build-2736575974"},"reference-count":23,"publisher":"American Chemical Society (ACS)","issue":"6","license":[{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>An untargeted multi-omics study implicated the potential dysregulation of fatty acid, nucleotide, and energy metabolism in the brainstems of spontaneously hypertensive rats (SHRs). A further quantitative exploration of the alterations in the metabolic pathways is necessary for a deep understanding of the central nervous system in SHRs. Targeted metabolic profiling of 40 fatty acids (PeptideAtlas: PASS01671) and 32 metabolites of nucleotides and energy metabolism (PeptideAtlas: PASS01672) and parallel reaction monitoring analysis of 5 proteins (PeptideAtlas: PASS01673) were performed on the brainstems of SHRs (n = 8, 11 weeks old) and normotensive Wistar rats (n = 8, age-matched) using gas chromatography\u2013mass spectrometry (GC\u2013MS) and liquid chromatography\u2013tandem MS. The targeted profiling results of metabolites and proteins revealed decreased polyunsaturated fatty acid (PUFA) synthesis with a significant downregulation of cis-11,14-eicosadienoic acid, cis-13,16-docosadienoic acid, and docosatetraenoate and impaired PUFA oxidation with the accumulation of \u03b3-linolenate induced by the significantly downregulated expression of 2,4-dienoyl-CoA reductase (p &amp;lt; 0.05). Dysregulated GTP and ATP metabolism was observed, with significantly decreased GDP and ADP (p &amp;lt; 0.05) correlated with reduced GTPases of guanine nucleotide-binding protein subunit beta-1 (GNB1), transforming protein RhoA (RHOA), and Rho-related GTP-binding protein RhoB (RHOB) in the brainstem of SHRs. In addition, protein-arginine deiminase type-2 was significantly reduced in the brainstems of SHRs (p &amp;lt; 0.05). The aberrant PUFA and energy metabolism might help to explain the alterations in the brainstem of SHRs. The findings on both metabolites and proteins could provide systemic insights into the pathology basis of altered PUFA and energy metabolism in hypertension, especially in the central nervous system.<\/jats:p>","DOI":"10.1021\/acs.jproteome.1c00208","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T17:00:26Z","timestamp":1621270826000},"page":"3305-3314","source":"Crossref","is-referenced-by-count":2,"title":["Targeted Metabolic\nProfiling and PRM Analysis of Proteins\nRevealed Impaired Polyunsaturated Fatty Acid Metabolism and GTP Metabolism\nin the Brainstem of Spontaneously Hypertensive Rats"],"prefix":"10.1021","volume":"20","author":[{"given":"Wenbin","family":"Zhou","sequence":"first","affiliation":[{"name":"Shanghai University of Traditional Chinese Medicine , , ,","place":["Shanghai, China, 201203"]},{"name":"Shanghai Zhulian Intelligent Technology Ltd. Co. , ,","place":["Shanghai, China, 201323"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bangjie","family":"Zhu","sequence":"additional","affiliation":[{"name":"Shanghai University of Traditional Chinese Medicine , , ,","place":["Shanghai, China, 201203"]},{"name":"Shanghai Jiao Tong University , , ,","place":["Shanghai, China, 200240"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Kou","sequence":"additional","affiliation":[{"name":"Shanghai University of Traditional Chinese Medicine , , ,","place":["Shanghai, China, 201203"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenglan","family":"Qi","sequence":"additional","affiliation":[{"name":"Shanghai University of Traditional Chinese Medicine , , ,","place":["Shanghai, China, 201203"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunming","family":"Lv","sequence":"additional","affiliation":[{"name":"Shanghai Zhulian Intelligent Technology Ltd. Co. , ,","place":["Shanghai, China, 201323"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3388-5485","authenticated-orcid":true,"given":"Yu","family":"Cheng","sequence":"additional","affiliation":[{"name":"Shanghai University of Traditional Chinese Medicine , , ,","place":["Shanghai, China, 201203"]},{"name":"Shanghai Jiao Tong University , , ,","place":["Shanghai, China, 200240"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Wei","sequence":"additional","affiliation":[{"name":"Shanghai University of Traditional Chinese Medicine , , ,","place":["Shanghai, China, 201203"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2021,5,17]]},"reference":[{"key":"2026081415115087500_cit1","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1161\/HYPERTENSIONAHA.107.102285","article-title":"Mitochondrial dysfunction in the\nhypertensive rat brain - Respiratory complexes exhibit assembly defects\nin hypertension","volume":"51","author":"Lopez-Campistrous","year":"2008","journal-title":"Hypertension"},{"key":"2026081415115087500_cit2","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/s0006-8993(03)03320-1","article-title":"Dietary fatty acids alter blood pressure,\nbehavior and brain membrane composition of hypertensive rats","volume":"988","author":"de\nWilde","year":"2003","journal-title":"Brain Res."},{"key":"2026081415115087500_cit3","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1007\/s11010-011-0711-y","article-title":"Temporal\nrelation of cardiac hypertrophy, oxidative stress, and fatty acid\nmetabolism in spontaneously hypertensive rat","volume":"351","author":"Purushothaman","year":"2011","journal-title":"Mol. Cell. Biochem."},{"key":"2026081415115087500_cit4","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1177\/0964528419828733","article-title":"Changes in cerebral\nglucose metabolism\nafter acupuncture at KI3 in spontaneously hypertensive rats: a positron\nemission tomography study","volume":"37","author":"Li","year":"2019","journal-title":"Acupunct. Med."},{"key":"2026081415115087500_cit5","doi-asserted-by":"publisher","first-page":"10","DOI":"10.2174\/156720212799297074","article-title":"Gene expression\nsuggests\nspontaneously hypertensive rats may have altered metabolism and reduced\nhypoxic tolerance","volume":"9","author":"Ritz","year":"2012","journal-title":"Curr. Neurovasc. Res."},{"key":"2026081415115087500_cit6","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1007\/s12031-015-0491-z","article-title":"Impaired\nEnergy Metabolism and Disturbed\nDopamine and Glutamate Signalling in the Striatum and Prefrontal Cortex\nof the Spontaneously Hypertensive Rat Model of Attention-Deficit Hyperactivity\nDisorder","volume":"56","author":"Dimatelis","year":"2015","journal-title":"J. Mol. Neurosci."},{"key":"2026081415115087500_cit7","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1161\/hypertensionaha.106.085589","article-title":"Junctional adhesion\nmolecule-1 is upregulated in spontaneously\nhypertensive rats: evidence for a prohypertensive role within the\nbrain stem","volume":"49","author":"Waki","year":"2007","journal-title":"Hypertension"},{"key":"2026081415115087500_cit8","doi-asserted-by":"publisher","first-page":"4114","DOI":"10.1021\/acs.jproteome.0c00585","article-title":"Integrative\nMetabolic and Proteomic Profiling of the Brainstem in\nSpontaneously Hypertensive Rats","volume":"19","author":"Cheng","year":"2020","journal-title":"J. Proteome\nRes."},{"key":"2026081415115087500_cit9","doi-asserted-by":"publisher","first-page":"2508","DOI":"10.1038\/s41467-020-16126-7","article-title":"2,4-dienoyl-CoA\nreductase regulates lipid homeostasis in treatment-resistant prostate\ncancer","volume":"11","author":"Blomme","year":"2020","journal-title":"Nat. Commun."},{"key":"2026081415115087500_cit10","doi-asserted-by":"publisher","first-page":"16","DOI":"10.3390\/jpm8020016","article-title":"Applicability of Precision Medicine\nApproaches to Managing Hypertension in Rural Populations","volume":"8","author":"Halladay","year":"2018","journal-title":"J. Pers. Med."},{"key":"2026081415115087500_cit11","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1021\/pr201001a","article-title":"Distinct urinary\nmetabolic profile of human colorectal cancer","volume":"11","author":"Cheng","year":"2012","journal-title":"J. Proteome Res."},{"key":"2026081415115087500_cit12","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1021\/pr3009385","article-title":"Quantitative\nproteome\nof medulla oblongata in spontaneously hypertensive rats","volume":"12","author":"Sun","year":"2013","journal-title":"J. Proteome Res."},{"key":"2026081415115087500_cit13","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1038\/s41419-020-02948-2","article-title":"Acyl-CoA thioesterase\n1 prevents cardiomyocytes from Doxorubicin-induced\nferroptosis via shaping the lipid composition","volume":"11","author":"Liu","year":"2020","journal-title":"Cell Death Dis."},{"key":"2026081415115087500_cit14","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1016\/j.talanta.2017.11.054","article-title":"A simultaneously quantitative\nmethod to profiling twenty endogenous\nnucleosides and nucleotides in cancer cells using UHPLC-MS\/MS","volume":"179","author":"Zhu","year":"2018","journal-title":"Talanta"},{"key":"2026081415115087500_cit15","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1007\/bf00618120","article-title":"Respiratory\nbursts at the midline of the rostral medulla of the lamprey","volume":"157","author":"Rovainen","year":"1985","journal-title":"J. Comp. Physiol., A"},{"key":"2026081415115087500_cit16","doi-asserted-by":"publisher","first-page":"3068","DOI":"10.1074\/jbc.m411069200","article-title":"Structure and reactivity\nof human mitochondrial 2,4-dienoyl-CoA reductase: enzyme-ligand interactions\nin a distinctive short-chain reductase active site","volume":"280","author":"Alphey","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2026081415115087500_cit17","doi-asserted-by":"publisher","DOI":"10.7554\/elife.54166","article-title":"Human DECR1 is an androgen-repressed\nsurvival factor that regulates PUFA oxidation to protect prostate\ntumor cells from ferroptosis","volume":"9","author":"Nassar","year":"2020","journal-title":"Elife"},{"key":"2026081415115087500_cit18","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.febslet.2004.06.073","article-title":"Nucleoside diphosphate\nkinase of Mycobacterium tuberculosis acts as GTPase-activating protein\nfor Rho-GTPases","volume":"571","author":"Chopra","year":"2004","journal-title":"FEBS Lett."},{"key":"2026081415115087500_cit19","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1161\/hh1801.096337","article-title":"Increased expression\nand activity of RhoA are associated\nwith increased DNA synthesis and reduced p27\u00ad(Kip1) expression in the\nvasculature of hypertensive rats","volume":"89","author":"Seasholtz","year":"2001","journal-title":"Circ. Res."},{"key":"2026081415115087500_cit20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4161\/sgtp.28846","article-title":"Involvement of Rho GTPases and their\nregulators in\nthe pathogenesis of hypertension","volume":"5","author":"Loirand","year":"2014","journal-title":"Small GTPases"},{"key":"2026081415115087500_cit21","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.ejmg.2017.11.010","article-title":"Novel GNB1 de novo\nmutation in a patient with neurodevelopmental disorder and cutaneous\nmastocytosis: Clinical report and literature review","volume":"61","author":"Szcza\u0142uba","year":"2018","journal-title":"Eur. J. Med. Genet."},{"key":"2026081415115087500_cit22","doi-asserted-by":"publisher","first-page":"R219","DOI":"10.1530\/erc-15-0556","article-title":"Androgen control of lipid metabolism\nin prostate cancer: novel insights and future applications","volume":"23","author":"Butler","year":"2016","journal-title":"Endocr. Relat. Canc."},{"key":"2026081415115087500_cit23","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1007\/s12031-016-0771-2","article-title":"Regulatory\nAlterations of Energy Homeostasis in Spontaneously Hypertensive Rats\n(SHR)","volume":"59","author":"Furedi","year":"2016","journal-title":"J. Mol. Neurosci."}],"container-title":["Journal of Proteome Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jproteome.1c00208","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/20\/6\/3305\/8429151\/pr1c00208.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/20\/6\/3305\/8429151\/pr1c00208.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T19:27:07Z","timestamp":1786735627000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jprobs\/article\/20\/6\/3305\/814842\/Targeted-Metabolic-Profiling-and-PRM-Analysis-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,17]]},"references-count":23,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,5,17]]},"published-print":{"date-parts":[[2021,6,4]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jproteome.1c00208","relation":{},"ISSN":["1535-3893","1535-3907"],"issn-type":[{"value":"1535-3893","type":"print"},{"value":"1535-3907","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,17]]}}}