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  • Khan, NomanUniv Karachi, HEJ Res Inst Chem, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan (author)

Dysregulation of metalloproteins in ischemic heart disease patients with systolic dysfunction

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • Elsevier,2023
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-498966
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-498966URI
  • https://doi.org/10.1016/j.ijbiomac.2023.123435DOI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Ischemic heart disease (IHD) is the leading cause of mortality worldwide. Metalloproteins have been linked to human health and diseases. The molecular functions of metalloproteins in IHD is not well understood and require further exploration. The objective of this study was to find out the role of metalloproteins in the pericardial fluid of IHD patients having normal (EF > 45) and impaired (EF < 45) left ventricular ejection fraction (LVEF). IHD patients were grouped into two categories: LVEF<45 (n = 12) and LVEF >45 (n = 33). Pooled samples of pericardial fluid were fractionated by using ZOOM-isoelectric focusing (IEF) followed by further processing using one-dimensional gel electrophoresis (1D SDS-PAGE) and filter-aided sample preparation (FASP). Tryptic peptides of each fraction and differential bands were then analyzed by nano-LC-ESI-MS/MS. Protein identification was performed through a Mascot search engine using NCBI-Prot and SwissProt databases. A total of 1082 proteins including 154 metalloproteins were identified. In the differential bands, 60 metalloproteins were identified, while 115 metalloproteins were identified in all ZOOM-IEF fractions. Twelve differentially expressed metalloproteins were selected in the intense bands according to their molecular weight (MW) and isoelectric point (pI). The 12 differentially expressed metalloprotein includes ceruloplasmin, Prothrombin, Vitamin K-dependent protein, Fibulin-1, Ribosomal protein S6 kinase alpha-6, nidogen, partial, Serum albumin, Hemopexin, C-reactive protein, Serum amyloid P-component, and Intelectin-1 protein which were all up-regulated while serotransferrin is the only metalloprotein that was down-regulated in impaired (LVEF<45) group. Among the metalloproteins, Zn-binding proteins are 36.5 % followed by Ca-binging 32.2 %, and Fe-binging 12.2 %. KEGG, pathway analysis revealed the association of ceruloplasmin and serotransferrin with the ferroptosis pathway. In conclusion, 154 metalloproteins were identified of them the Zn-binding protein followed by Ca-binding and Fe-binding proteins were the most abundant metalloproteins. The two metalloproteins, the Cu-binding protein ceruloplasmin, and Fe-binding protein serotransferrin are involved in the ferroptosis pathway, an iron-dependent form of regulated cell death that has been linked to cardiac pathology, especially in IHD patients having impaired systolic (LVEF<45) dysfunction. However, further research is required to validate these findings.

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  • Ullah, JunaidUniv Karachi, HEJ Res Inst Chem, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan (author)
  • Hashmi, SatwatAgha Khan Univ, Dept Biol & Biomed Sci, Karachi 74800, Pakistan (author)
  • Ali, ArslanUniv Karachi, Dr Panjwani Ctr Mol Med & Drug Res, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan (author)
  • Siddiqui, Amna JabbarUniv Karachi, Dr Panjwani Ctr Mol Med & Drug Res, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan (author)
  • Sami, Shahid AhmedAga Khan Univ Hosp, Dept Surg, Karachi 74800, Pakistan (author)
  • Bokhari, Syeda SairaAga Khan Univ Hosp, Dept Med, Karachi 74800, Pakistan (author)
  • Sharif, HasanatAga Khan Univ Hosp, Dept Surg, Karachi 74800, Pakistan (author)
  • Uddin, JalalKing Khalid Univ, Coll Pharm, Dept Pharmaceut Chem, Asir 61421, Saudi Arabia (author)
  • El-Seedi, HeshamUppsala universitet,Institutionen för farmaceutisk biovetenskap,Farmakognosi(Swepub:uu)heels173 (author)
  • Musharraf, Syed GhulamUniv Karachi, HEJ Res Inst Chem, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan.;Univ Karachi, Dr Panjwani Ctr Mol Med & Drug Res, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan (author)
  • Univ Karachi, HEJ Res Inst Chem, Int Ctr Chem & Biol Sci, Karachi 75270, PakistanAgha Khan Univ, Dept Biol & Biomed Sci, Karachi 74800, Pakistan (creator_code:org_t)

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  • In:International Journal of Biological Macromolecules: Elsevier2320141-81301879-0003

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