01672nas a2200265 4500008004100000022001400041245010700055210006900162260007500231300001000306490000600316520072300322653001701045653002101062653002701083653001601110100001601126700002101142700002501163700002501188700002301213700002601236700002001262856012401282 2012 eng d a1862-834600aDynamic proteome in enigmatic preeclampsia: an account of molecular mechanisms and biomarker discovery0 aDynamic proteome in enigmatic preeclampsia an account of molecul aPOSTFACH 101161, 69451 WEINHEIM, GERMANYbWILEY-V C H VERLAG GMBHcJAN a79-900 v63 a

The coevolution of genomics and proteomics has led to advancements in the field of diagnosis and molecular mechanisms of disease. Proteomics is now stepping into the field of obstetrics, where early diagnosis of pregnancy complication such as preeclampsia (PE) is imperative. PE is a multifactorial disease characterized by hypertension with proteinuria, which is a leading cause of maternal and neonatal morbidity and mortality occurring in 5-7% of pregnancies worldwide. This review discusses the probable molecular mechanisms that lead to PE and summarizes the proteomics research carried out in understanding the pathogenicity of PE, and for identifying the candidate biomarker for diagnosis of the disease.

10aHypertension10aOxidative stress10aPregnancy complication10aProteinuria1 aMary, Sheon1 aPatil, Gouri, V.1 aKulkarni, Asmita, V.1 aKulkarni, Mahesh, J.1 aJoshi, Sadhana, R.1 aMehendale, Savita, S.1 aGiri, Ashok, P. uhttps://library.ncl.res.in/content/dynamic-proteome-enigmatic-preeclampsia-account-molecular-mechanisms-and-biomarker-001301nas a2200241 4500008004100000022001400041245005300055210005200108260007500160300001200235490000600247520057000253653001000823653001300833653001400846653000900860100002500869700002300894700001600917700002500933700002000958856008100978 2013 eng d a1862-834600aGlycated proteome: from reaction to intervention0 aGlycated proteome from reaction to intervention aPOSTFACH 101161, 69451 WEINHEIM, GERMANYbWILEY-V C H VERLAG GMBHcJAN a155-1700 v73 a

Glycation, a nonenzymatic reaction between reducing sugars and proteins, is a proteome wide phenomenon, predominantly observed in diabetes due to hyperglycemia. Glycated proteome of plasma, kidney, lens, and brain are implicated in the pathogenesis of various diseases, including diabetic complications, neurodegenerative diseases, cancer, and aging. This review discusses the strategies to characterize protein glycation, its functional implications in different diseases, and intervention strategies to protect the deleterious effects of protein glycation.

10aaging10aDiabetes10aGlycation10aRAGE1 aKulkarni, Mahesh, J.1 aKorwar, Arvind, M.1 aMary, Sheon1 aBhonsle, Hemangi, S.1 aGiri, Ashok, P. uhttps://library.ncl.res.in/content/glycated-proteome-reaction-intervention-001848nas a2200253 4500008004100000022001400041245005200055210005200107260007700159300001000236490000600246520106800252653001701320653002401337653001901361653002101380653000901401100001701410700001601427700002001443700002001463700002501483856008601508 2014 eng d a1862-834600aImmune response to chemically modified proteome0 aImmune response to chemically modified proteome aBOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANYbWILEY-V C H VERLAG GMBHcFEB a19-340 v83 a

Both enzymatic and nonenzymatic PTMs of proteins involve chemical modifications. Some of these modifications are prerequisite for the normal functioning of cell, while other chemical modifications render the proteins as neo-self antigens, which are recognized as non-self leading to aberrant cellular and humoral immune responses. However, these modifications could be a secondary effect of autoimmune diseases, as in the case of type I diabetes, hyperglycemia leads to protein glycation. The enigma of chemical modifications and immune response is akin to the chick-and-egg paradox. Nevertheless, chemical modifications regulate immune response. In some of the well-known autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis, chemically modified proteins act as autoantigens forming immune complexes. In some instances, chemical modifications are also involved in regulating immune response during pathogen infection. Further, the usefulness of proteomic analysis of immune complexes is briefly discussed.

10aAutoantibody10aAutoimmune diseases10aImmune complex10aImmunoproteomics10aPTMs1 aBhat, Shweta1 aMary, Sheon1 aBanarjee, Reema1 aGiri, Ashok, P.1 aKulkarni, Mahesh, J. uhttps://library.ncl.res.in/content/immune-response-chemically-modified-proteome-001559nas a2200181 4500008004100000245007800041210006900119260000800188300001200196490000700208520094600215100001601161700002501177700002601202700002301228700002001251856010601271 2017 eng d00a Differential accumulation of vimentin fragments in preeclamptic placenta0 aDifferential accumulation of vimentin fragments in preeclamptic  cNOV a420-4250 v743 aPreeclampsia is a pregnancy complication that is the result of abnormal placentation because of inadequate trophoblast invasion into spiral arteries that prevent normal blood flow to the placenta. We report the alteration in vimentin protein proteolysis in placenta of normotensive and preeclamptic women, which is known to have a role in many physiological functions other than its major function in the structural integrity of the cell. Placental proteome from normotensive (n=25) and preeclamptic pregnancies (n=25) showed eight differentially accumulated protein spots of vimentin (proteolytic fragments) by two-dimensional electrophoresis. Immunoblots of normotensive and preeclamptic placenta revealed a difference in proteolytic processing of vimentin. In particular, lower molecular weight vimentin fragments of 32 and 20 kDa were 3.3 and 2.6-fold (p<0.0001) higher, respectively, in preeclampsia compared with normotensive placenta.1 aMary, Sheon1 aKulkarni, Mahesh, J.1 aMehendale, Savita, S.1 aJoshi, Sadhana, R.1 aGiri, Ashok, P. uhttps://library.ncl.res.in/content/differential-accumulation-vimentin-fragments-preeclamptic-placenta02108nas a2200193 4500008004100000245012100041210006900162260000800231300001400239490000700253520138400260100001601644700002501660700002201685700003101707700002601738700002001764856013001784 2017 eng d00aPlacental proteomics provides insights into pathophysiology of pre-eclampsia and predicts possible markers in plasma0 aPlacental proteomics provides insights into pathophysiology of p cFEB a1050-10600 v163 a

Pre-eclampsia is a hypertensive disorder characterized by the new onset of hypertension >140/90 mmHg and proteinuria after the 20th week of gestation. The disorder is multi-factorial and originates with abnormal placentation. Comparison of the placental proteome of normotensive (n=25) and pre-eclamptic (n=25) patients by gel-free proteomic techniques, identified a total of 2145 proteins in the placenta of which 180 were differentially expressed (>1.3 fold, p<0.05). Gene ontology enrichment analysis of biological process suggested that the differentially expressed proteins belonged to various physiological processes such as angiogenesis, apoptosis, oxidative stress, hypoxia, placental development, which are implicated in the pathophysiology of pre-eclampsia. Some of the differentially expressed proteins were monitored in the plasma by multiple reaction monitoring (MRM) analysis, which showed an increase in Apolipoprotein AI and AII in gestational week 26-30th (2-fold, p<0.01) while haptoglobin and hemopexin decreased in gestational week 26-30th and 40th week/at delivery (1.8 fold, p<0.01) in pre-eclamptic patients. This study provides a proteomic insight into the pathophysiology of pre-eclampsia. Identified candidate proteins can be evaluated further for the development of potential biomarkers associated with pre-eclampsia pathogenesis.

1 aMary, Sheon1 aKulkarni, Mahesh, J.1 aMalakar, Dipankar1 aJoshi, Sadhana, Ramchandra1 aMehendale, Savita, S.1 aGiri, Ashok, P. uhttps://library.ncl.res.in/content/placental-proteomics-provides-insights-pathophysiology-pre-eclampsia-and-predicts-possible02596nas a2200265 4500008004100000022001400041245010200055210006900157260000800226300000900234490000700243520175900250653001702009653001102026653001502037653001402052653001502066100001602081700002702097700001802124700002002142700001602162700002202178856013002200 2017 eng d a0194-911X00aPolymerization-incompetent uromodulin in the pregnant stroke-prone spontaneously hypertensive rat0 aPolymerizationincompetent uromodulin in the pregnant strokeprone cMAY a910+0 v693 a

The kidney is centrally involved in blood pressure regulation and undergoes extensive changes during pregnancy. Hypertension during pregnancy may result in an altered urinary peptidome that could be used to indicate new targets of therapeutic or diagnostic interest. The stroke-prone spontaneously hypertensive rat (SHRSP) is a model of maternal chronic hypertension. Capillary electrophoresis-mass spectrometry was conducted to interrogate the urinary peptidome in SHRSP and the control Wistar-Kyoto strain at three time points: prepregnancy and gestational days 12 and 18. The comparison within and between the Wistar-Kyoto and SHRSP peptidome at all time points detected 123 differentially expressed peptides (fold change >1.5; P<0.05). Sequencing of these peptides identified fragments of collagen a-chains, albumin, prothrombin, actin, serpin A3K, proepidermal growth factor, and uromodulin. Uromodulin peptides showed a pregnancy-specific alteration in SHRSP with a 7.8-fold (P<0.01) and 8.8-fold (P<0.05) increase at gestational days 12 and 18, respectively, relative to the Wistar-Kyoto. Further investigation revealed that these peptides belonged to the polymerization-inhibitory region of uromodulin. Two forms of uromodulin (polymerization competent and polymerization incompetent) were found in urine from both Wistar-Kyoto and SHRSP, where the polymerizationincompetent form was increased in a pregnancy-specific manner in SHRSP. Nifedipine-treated pregnant SHRSP showed only polymerization-competent uromodulin, indicating that calcium may be mechanistically involved in uromodulin polymerization. This study highlights, for the first time, a potential role of uromodulin and its polymerization in hypertensive pregnancy.

10aHypertension10aKidney10aNifedipine10apregnancy10auromodulin1 aMary, Sheon1 aSmall, Heather, Yvonne1 aSiwy, Justyna1 aMullen, William1 aGiri, Ashok1 aDelles, Christian uhttps://library.ncl.res.in/content/polymerization-incompetent-uromodulin-pregnant-stroke-prone-spontaneously-hypertensive-rat00645nas a2200169 4500008004100000245010900041210006900150260000800219300001100227490000800238100002000246700002300266700001600289700001700305700002200322856013100344 2017 eng d00aResistin mediates sex-dependent effects of perivascular adipose tissue on vascular function in the shrsp0 aResistin mediates sexdependent effects of perivascular adipose t cAPR a A3-A30 v1031 aMcNeilly, Sarah1 aSmall, Heather, Y.1 aMary, Sheon1 aSheikh, Adam1 aDelles, Christian uhttps://library.ncl.res.in/content/resistin-mediates-sex-dependent-effects-perivascular-adipose-tissue-vascular-function-shrsp01944nas a2200181 4500008004100000245011200041210006900153260000800222300002200230490000700252520126400259100001601523700002501539700002601564700002301590700002001613856012901633 2017 eng d00aTubulointerstitial nephritis antigen-like 1 protein is downregulated in the placenta of pre-eclamptic women0 aTubulointerstitial nephritis antigenlike 1 protein is downregula cMAR aArticle Number: 80 v143 aBackground: Tubulointerstitial nephritis antigen-like 1 protein (TINAGL1), is a matricellular protein, known to play role in cell adhesion and cell receptor interaction. Research related to TINAGL1 is limited to cell culture and animal models. Demonstration of TINAGL1 as a positive regulator of angiogenesis and its expression in the decidua of postimplantation mouse uterus, prompted us to validate its expression in human placenta during impaired angiogenesis in pre-eclamptic condition. Methods: Placental tissue from normotensive (n = 25) and pre-eclamptic (n = 25) pregnancies were used to study the differentially expressed proteins by two-dimensional gel electrophoresis and TINAGL1 protein was validated with Western blotting. Results: A total of 55 protein spots were differentially expressed (fold change > 1.5, p < 0.05), of which 27 were upregulated and 28 were downregulated in the pre-eclamptic placenta. TINAGL1 was found to be downregulated in pre-eclamptic compared to normotensive pregnant women. Conclusion: This is the first study reporting TINAGL1 to be present in human placenta and differentially expressed in pre-eclamptic condition. The functional role of TINAGL1 in association to human pregnancy needs to be explored further.1 aMary, Sheon1 aKulkarni, Mahesh, J.1 aMehendale, Savita, S.1 aJoshi, Sadhana, R.1 aGiri, Ashok, P. uhttps://library.ncl.res.in/content/tubulointerstitial-nephritis-antigen-1-protein-downregulated-placenta-pre-eclamptic-women