Purification and mechanism of action of “cortexin,” a novel antihypertensive protein hormone from kidney and its role in essential hypertension in men

Chakraborty, Somashree; Khan, Gausal A.; Karmohapatra, Soumendra K.; Bhattacharya, Raja; Bhattacharya, Gourav; Sinha, Asru K.

doi:10.1016/j.jash.2008.11.002

Cited by 9 publications

(15 citation statements)

References 25 publications

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“…Endothelial cells from the carotid artery of the freshly slaughtered goat was prepared in Tyrod's buffer pH 7.4 as described before [37]. The disrupted cell mass was centrifuged at 60,000 g for 30 min at 0°C.…”

Section: Methodsmentioning

confidence: 99%

Reduction of Death Rate Due to Acute Myocardial Infarction in Subjects with Cancers through Systemic Restoration of Impaired Nitric Oxide

et al. 2014

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IntroductionExcessive aggregation of platelets at the site of plaque rupture on the coronary artery led to the formation of thrombus which is reported to precipitate acute myocardial infarction (AMI). Nitric oxide (NO) has been reported to inhibit platelet aggregation and induce thrombolysis through the in situ formation of plasmin. As the plasma NO level in AMI patients from two different ethnic groups was reduced to 0 µM (median) compared to 4.0 µM (median) in normal controls, the effect of restoration of the NO level to normal ranges on the rate of death due to AMI was determined.Methods and ResultsThe restoration of plasma NO level was achieved by a sticking small cotton pad (10×25 mm) containing 0.28 mmol sodium nitroprusside (SNP) in 0.9% NaCl to the abdominal skin of the participants using non-toxic adhesive tape which was reported to normalize the plasma NO level. The participants (8,283) were volunteers in an independent study who had different kinds of cancers and did not wish to use any conventional therapy for their condition but opted to receive SNP “pad” for their condition for 3 years.The use of SNP “pad” which normalized (≈4.0 µM) the plasma NO level that in consequence reduced the death rate due to AMI, among the participants, was found to be significantly reduced compared to the death due to AMI in normal population.ConclusionOur data suggested that the use of SNP “pad” significantly reduced the death due to AMI.Trial Registration www.ctri.nic.in 004236

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Section: Methodsmentioning

confidence: 99%

Reduction of Death Rate Due to Acute Myocardial Infarction in Subjects with Cancers through Systemic Restoration of Impaired Nitric Oxide

et al. 2014

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“…Cortexin 3 ( Ctxn3 , 93% reduction in expression) – originally isolated from goat renal cortex – is a cardioprotective endogenous activator of eNOS that may play a role in the pathogenesis of hypertension [46]. Cortexin-3 expression was decreased in diabetic kidney, which also exhibits impaired endothelial NO generation.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome-Based Analysis of Kidney Gene Expression Changes Associated with Diabetes in OVE26 Mice, in the Presence and Absence of Losartan Treatment

Komers

et al. 2014

PLoS ONE

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Diabetes is among the most common causes of end-stage renal disease, although its pathophysiology is incompletely understood. We performed next-generation sequencing-based transcriptome analysis of renal gene expression changes in the OVE26 murine model of diabetes (age 15 weeks), relative to non-diabetic control, in the presence and absence of short-term (seven-day) treatment with the angiotensin receptor blocker, losartan (n = 3–6 biological replicates per condition). We detected 1438 statistically significant changes in gene expression across conditions. Of the 638 genes dysregulated in diabetes relative to the non-diabetic state, >70% were downregulation events. Unbiased functional annotation of genes up- and down-regulated by diabetes strongly associated (p<1×10−8) with terms for oxidative stress and for endoplasmic reticulum stress/protein folding. Most of the individual gene products up- or down-regulated with diabetes were unaffected by losartan treatment; however, of the gene products dysregulated in diabetes and influenced by losartan treatment, the vast majority of changes were in the direction of amelioration rather than exacerbation of the diabetic dysregulation. This group of losartan-protected genes associated strongly with annotation terms for endoplasmic reticulum stress, heat shock proteins, and chaperone function, but not oxidative stress; therefore, the losartan-unaffected genes suggest avenues for additional therapeutic opportunity in diabetes. Interestingly, the gene product most highly upregulated by diabetes (>52-fold), encoded by the cationic amino acid transporter Slc7a12, and the gene product most highly downregulated by diabetes (>99%) – encoded by the “pseudogene” Gm6300 – are adjacent in the murine genome, are members of the SLC7 gene family, and are likely paralogous. Therefore, diabetes activates a near-total genetic switch between these two paralogs. Other individual-level changes in gene expression are potentially relevant to diabetic pathophysiology, and novel pathways are suggested. Genes unaffected by diabetes alone but exhibiting increased renal expression with losartan produced a signature consistent with malignant potential.

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“…The numbers of physiologic stimulators for the eNOS currently reported are however limited. Only a kidney-cortex-derived hypotensive protein called renal cortexin [25] and insulin [11] are currently known to activate eNOS in the endothelial cells homogenate in vitro . As reported in Section 3, dermcidin was a potent inhibitor of insulin-induced activated eNOS that led to the inhibition of systemic NO synthesis in the endothelial cells homogenate.…”

Section: Discussionmentioning

confidence: 99%

“…Endothelial cells were prepared from the carotid artery of the freshly slaughtered goat as described before [25]. The endothelial cell suspension in Tyrod's buffer pH 7.4 was disrupted by repeated freezing and thawing the cell suspension (20 mg/mL) in liquid N 2 [25].…”

Section: Methodsmentioning

confidence: 99%

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The Role of Dermcidin Isoform 2: A Two-Faceted Atherosclerotic Risk Factor for Coronary Artery Disease and the Effect of Acetyl Salicylic Acid on It

et al. 2012

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Hypertension and diabetes mellitus are considered to be two major atherosclerotic risk factors for coronary artery disease (CAD). A stress-induced protein identified to be dermcidin isoform 2 of Mr. 11 kDa from blood plasma of hypertensive persons when injected (0.1 μM) in rabbits increased the systolic pressure by 77% and diastolic pressure by 45% over the controls within 2 h. Ingestion of acetyl salicylic acid (150 mg/70 kg) by these subjects reduced systolic (130 mm Hg) and diastolic pressures (80 mm Hg) with reduction of plasma dermcidin level to normal ranges (9 nM). The protein was found to be a potent activator of platelet cyclooxygenase and inhibited insulin synthesis. Aspirin was found to reduce hypertension by reduction of plasma dermcidin level, neutralized the effect of cyclooxygenase, and restored the pancreatic insulin synthesis through NO synthesis. These results indicated that dermcidin could be a novel atherosclerotic risk factor for its hypertensive and diabetogenic effects.

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Purification and mechanism of action of “cortexin,” a novel antihypertensive protein hormone from kidney and its role in essential hypertension in men

Cited by 9 publications

References 25 publications

Reduction of Death Rate Due to Acute Myocardial Infarction in Subjects with Cancers through Systemic Restoration of Impaired Nitric Oxide

Reduction of Death Rate Due to Acute Myocardial Infarction in Subjects with Cancers through Systemic Restoration of Impaired Nitric Oxide

Transcriptome-Based Analysis of Kidney Gene Expression Changes Associated with Diabetes in OVE26 Mice, in the Presence and Absence of Losartan Treatment

The Role of Dermcidin Isoform 2: A Two-Faceted Atherosclerotic Risk Factor for Coronary Artery Disease and the Effect of Acetyl Salicylic Acid on It

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