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PubMed1998

Circulatory response to hyperthermia during acute normovolaemic haemodilution.

Cats anaesthetized with a mixture of chloralose and urethane were exposed to heat stress in two groups. In the first group (n = 10) of control animals, the effect of heat stress on haemodynamic variables was recorded at control haematocrit (HCT) of 42.0 +/- 1.0%. In a second group, the effect of heat stress was studied after induction of acute normovolaemic haemodilution (HCT of 13.0 +/- 1.0%). Haemodilution was induced to a maximum of 60% replacement of blood with dextran (mol.wt. 150,000). Heat stress was induced by surface heating and core body temperature was raised from 37 degrees C to 42 degrees C. The effect of heat stress and haemodilution on various haemodynamic variables, viz. left ventricular pressure (LVP), left ventricular contractility (LVdP/dtmax), heart rate (HR), cardiac output (CO), arterial blood pressure (ABP), right atrial pressure (RAP), and arterial blood PO2, PCO2 and pH was examined. Haemodilution produced significant (P < 0.05) increases in HR and CO but there were no significant (P > 0.05) changes in ABP, RAP, LVdP/dtmax and total peripherial resistance (TPR). Hyperthermia caused a significant fall (P < 0.05) in TPR. However, the percentage fall in TPR was higher in the control group. On exposure to heat stress, there were significant (P < 0.05I increases in HR and CO in both the groups; however, HR and CO values were significantly (P < 0.05) higher in the haemodiluted group compared to the control. The latter findings could be due either to the higher basal values of these variables with the fall in HCT or to inefficient cardiovascular regulatory mechanisms. The lack of efficient regulatory control under such severe stress conditions makes the cardiovascular system of anaemic animals more vulnerable to heat stress. In conclusion, the results of the present study showed deleterious effects of heat stress in both the groups. The higher values of HR and CO in the haemodiluted group may be responsible for circulatory failure at low HCT values, indicating a higher risk in the haemodiluted group as compared to the control group.

Anemia↗

PubMed1983

How diuretics lower blood pressure.

Thiazides produce an average loss of 2 L of extracellular fluid volume, of which about 300 ml is plasma volume, during the first 48 hours of administration, and this reduction is maintained without further loss for as long as the drug is given. Do thiazides lower blood pressure by volume depletion or by direct vasodilator action? As evidence against the vasodilator theory, these facts may be adduced: (1) thiazides do not lower blood pressure in patients (with renal disease) who cannot obtain a diuresis, and (2) other diuretics and diets very low in sodium also reduce blood pressure and volume to a similar degree. A related hypothesis is that thiazides reduce total peripheral vascular resistance (TPR) by "dehydrating" vascular walls. However, direct measurements in small arteries failed to confirm such changes. There is, however, a fall in TPR after long-term treatment, although initially cardiac output falls and TPR remains unchanged. How these long-term readjustments occur remains unknown, although several hypotheses have been advanced.

Benzothiadiazines↗

PubMed1986

Systemic and renal vasodilation after beta-adrenoceptor blockade with pindolol: a hemodynamic study on the onset and maintenance of its antihypertensive effect.

Pindolol, a beta blocker with considerable partial agonist activity (PAA), was studied in 10 hypertensive subjects. The maximal fall in mean arterial pressure (MAP) was seen 3 to 4 hours after oral dosing with 10 mg of pindolol (-15 +/- 3%, mean +/- SEM). This was caused by a reduction in total peripheral resistance (TPR), which amounted to 25 +/- 4% after 24 hours. Cardiac output increased by 16 +/- 5%. Cardiac filling pressures and pulmonary artery pressure did not change. Increasing the dose of pindolol, from 5 mg twice a day to 15 mg twice a day over a 3-week period, caused no further change in MAP. After 3 weeks, the fall in MAP (-11 +/- 2%) was maintained by reduced TPR (-26 +/- 6%), whereas cardiac output and stroke volume were increased by 16 +/- 6% and 26 +/- 6%. Renal blood flow and glomerular filtration rate did not change. Beta blockers devoid of PAA lower cardiac output, whereas the elevated TPR in hypertension is unchanged. The hemodynamic profile of pindolol essentially differs from that of beta blockers devoid of PAA.

Adrenergic beta-Antagonists↗

PubMed1988

Noninvasive study of cardiac structure and function after rilmenidine for essential hypertension.

The hemodynamic effects of rilmenidine (S 3341) were evaluated noninvasively by aortic Doppler velocimetry, M-mode echocardiography and phonocardiography in hypertensive patients treated for 28 days. After a 2-week placebo run-in period, patients with mild hypertension (group I, n = 8, mean diastolic blood pressure [BP] = 97.18 +/- 0.65 mm Hg) received 1 mg of rilmenidine each morning and patients with moderate hypertension (group II, n = 6, mean diastolic BP = 107.62 +/- 1.18 mm Hg) received 1 mg twice daily. The hemodynamic variations in both groups after the first administration (day 1) showed that during the first 3 hours, mean arterial pressure and cardiac index (CI) were significantly reduced, whereas total peripheral resistance (TPR) was increased. From the third to the fifth hour, the decrease in mean arterial pressure was maintained, CI was higher than initial values and TPR decreased, indicating a persistent vasodilator effect. On day 28, hemodynamic variations were similar but of a lower amplitude. Before administration on day 28, a significant decrease in systolic and diastolic BP was observed, demonstrating that the antihypertensive activity of 1 mg was maintained for 24 hours, with a significant reduction in TPR and no modification of CI or stroke index. The M-mode and phonocardiographic left ventricular function indexes remained unchanged. Rilmenidine has a prolonged antihypertensive activity with a chronic vasodilator effect and no negative inotropic effect.

Adrenergic alpha-Agonists↗

PubMed1990

Effects of dopamine D1 and dopamine D2 receptor agonists on coronary and peripheral hemodynamics.

This study evaluated the coronary dopamine receptors by using the dopamine D1 receptor agonist fenoldopam, dopamine D2 receptor agonist propylbutyldopamine, and their selective antagonists SCH23390 and domperidone. Left circumflex coronary flow (CF), coronary perfusion pressure at constant flow, left ventricular hemodynamics, and total peripheral vascular resistance (TPR) were measured in pentobarbital-anesthetized dogs at constant arterial pressures. At doses of 200, 500 and 5000 nM, both fenoldopam and propylbutyldopamine induced dose-related inotropic effects, as evidenced by maximal dp/dt and cardiac output, an increase in CF, decrease in coronary vascular resistance and a decrease in TPR. Fenoldopam was more potent in its cardiac and coronary effects while propylbutyldopamine was more potent peripherally. On the basis of dosage used, the positive inotropic effects of fenoldopam and propylbutyldopamine were much weaker than dopamine. After beta-receptor blockade, the inotropic and coronary effects of fenoldopam and propylbutyldopamine were extremely attenuated. Domperidone could largely antagonize the propylbutyldopamine-induced inotropic and coronary effects while SCH23390 showed no significant effect. In addition, under our experimental conditions, the fenoldopam- and propylbutyldopamine-induced decreases in TPR were markedly reduced by SCH23390 and domperidone, respectively. The results indicate that the coronary effects of fenoldopam and propylbutyldopamine result not from a primary coronary vasodilating action, but from vasodilation secondary to positive inotropic effects. Both dopamine D1 and dopamine D2 receptors are involved in the peripheral vascular hemodynamics.

Animals↗

PubMed1987

Cardiac and hemodynamic responses to synthetic atrial natriuretic factor in rats.

To determine the hemodynamic effects of a hypotensive dose of atrial natriuretic factor (ANF), a synthetic peptide containing 26 amino acids of endogenous rat ANF (Arg-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly -Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-COOH) was studied in two groups of barbiturate anesthetized rats. In the first experiment, a 20-minute infusion of a hypotensive dose, 95 pmole/min i.v., of the synthetic ANF decreased mean arterial pressure (MAP) by 40 +/- 3 mm Hg from a baseline of 128 +/- 5 mm Hg, and cardiac output (CO) (microsphere method) by 7.8 +/- 1.8 ml/min/100 gm from a baseline of 23.5 +/- 1.3 ml/min/100 gm. Synthetic ANF did not significantly affect the total peripheral resistance (TPR) measured at the end of the 20-minute infusion. Sodium nitroprusside (SNP), infused at an equihypotensive dose of 20 micrograms/kg/min i.v., produced the same hemodynamic profile in seven other animals; in contrast, 0.3 mg/kg i.v. of hydralazine (n = 7) lowered MAP by 56 +/- 6 mm Hg and reduced TPR index by 3.0 +/- 0.6 mm Hg/ml/min/100 gm, but did not change CO. Other than an increase in coronary blood during SNF infusion, there were no significant changes in the distribution of cardiac output. Infusion of the saline vehicle had no significant effects on any of these parameters. The results of the second experiment in anesthetized rats confirmed that hypotensive doses of 40 and 100 pmole/kg/min i.v. lowered CO (dye dilution method) from a baseline of 33 +/- 6 to a minimum of 24 +/- 2 ml/min/100 gm (p less than 0.05) without affecting TPR. In addition, synthetic ANF did not significantly affect heart rate (HR) but it slightly reduced cardiac contractility (dp/dt50). These results suggest that the hypotensive dose of synthetic ANF reduced cardiac output, partially by diminishing stroke volume, and perhaps contractility.

Animals↗

PubMed1984

Cardiovascular responses to an isosterically modified prostaglandin analog in conscious dogs.

The cardiovascular effects of oral and intravenous administration of 0.05 and 0.1 mg/kg of the isosterically modified prostaglandin (PG) analog, (+)- 4-(3-[3-[2-(1-hydroxycyclohexyl)ethyl]-4-oxo-thiazolidinyl] propyl) benzoic acid were ascertained in conscious mongrels. After 0.05 mg/kg p.o., mean arterial pressure (MAP), obtained from indwelling catheters, fell from 105 +/- 1 to 100 +/- 4 mm Hg and total peripheral resistance (TPR) decreased from 0.062 +/- 0.006 to 0.039 +/- 0.002 mm Hg/ml/min. Cardiac output (CO), measured via electromagnetic flow probes, rose from 1.8 +/- 0.2 to 2.6 +/- 0.1 l/min and heart rate from 109 +/- 13 to 128 +/- 8 beats/min. The 0.1 mg/kg p.o. dose produced similar results. Intravenous injection of 0.1 mg/kg immediately dropped MAP from 103 +/- 6 to 58 +/- 3 mm Hg and TPR from 0.049 +/- .006 to .014 +/- .002 mm Hg/ml/min. CO climbed from 2.3 +/- 0.2 to 5.3 +/- 0.5 l/min and HR increased from 126 +/- 9 to 254 +/- 14 beats/min. Stroke volume was not affected by either oral or intravenous administration of the PG analog. Pretreatment with 100 micrograms/kg timolol blunted the CO and HR responses to 0.1 mg/kg iv of the PG analog without affecting the depressor response. Metaraminol infused during injection of 0.1 mg/kg iv of the PG analog diminished all responses. When compared to the cardiovascular effects of hydralazine and nitroprusside, the profile of the PG analog activity closely resembled that produced by the arterial vasodilator, hydralazine; in contrast, nitroprusside (which also dilates veins) reduced stroke volume, but did not significantly affect HR. In conclusion, dilation of the resistance vessels by the PG analog decreased MAP and TPR and reflexly elevated CO and HR in conscious dogs.

Animals↗

PubMed1986

Mechanism of met oncogene activation.

The met oncogene activated in vitro by treatment of a human osteogenic sarcoma (HOS) cell line with N-methyl-N'-nitronitrosoguanidine (MNNG) is related to the tyrosine kinase gene family. Probes from the met oncogene locus recognize two distinct transcripts of 9.0 kb and 10.0 kb which are independently expressed in a cell-type-specific fashion. While the met proto-oncogene locus expresses the 9.0 kb RNA and maps to human chromosome 7q21-31, the locus expressing the 10.0 kb RNA, (tpr; translocated promoter region) maps to human chromosome 1. Both MNNG-HOS cells and met NIH 3T3 transformants express a novel 5.0 kb RNA which represents a hybrid transcript with 5' sequences derived from tpr and 3' sequences from the met proto-oncogene. Treating HOS cells in vitro with MNNG, a known clastogenic carcinogen, resulted in fusion of two chromosomally disparate loci, met and tpr, generating the active met oncogene.

Cell Line↗

PubMed1990

A repeating amino acid motif in CDC23 defines a family of proteins and a new relationship among genes required for mitosis and RNA synthesis.

We have identified and characterized a novel, repeating 34 amino acid motif (the TPR motif) that is reiterated several times within the CDC23 gene product of S. cerevisiae. Multiple copies of this motif were discovered in five other proteins, three encoded by cell division cycle genes required to complete mitosis and two involved in RNA synthesis. Quantitative sequence analyses suggest the existence of a common underlying structure in each TPR unit that consists of amphipathic alpha-helical regions punctuated by proline-induced turns. The TPR motif defines a new family of genes and an important structural unit common to several proteins whose functions are required for mitosis and RNA synthesis.

Amino Acid Sequence↗

PubMed1983

Cardiovascular effects of simulated zero-gravity in humans.

UNLABELLED: Head-down and head-up [correction of heat-up] tilted bedrest (5 degrees) and head out water immersion (HOWI) for 6 hr were compared. PARAMETERS: Cardiac output (rebreathing method), blood pressure (arm cuff), forearm blood flow (venous occlusion plethysmography), total peripheral (TPR), and forearm vascular (FVR) resistances, Hct, Hb, relative plasma volume (PV) changes, and plasma catecholamines (single-isotope assay). During HOWI there was as expected a decrement in TPR, FVR, Mean arterial pressure (MAP, from 100 to 80 mmHg), Hct, and PV, and--as a new finding--catecholamines, which were 30-50% lower compared with both +5 and -5 degrees bedrest. During head down tilt, MAP was elevated (to 100-110 mmHg) and catecholamines did not fall, while TPR and EVR slowly decreased over 6 hr. HOWI is a stronger stimulus than -5 degrees bedrest, probably because HOWI elevates central venous pressure more markedly emptying the peripheral veins, while bedrest permits a distension of veins, which induces an increase in sympathetic nervous activity.

Adaptation, Physiological↗

PubMed1990

Peptide analogs of thymopentin distinguish distinct thymopoietin receptor specificities on two human T cell lines.

Thymopoietin, a polypeptide hormone of the thymus, and the synthetic pentapeptide thymopentin, corresponding to thymopoietin32-36, both induced elevations of intracellular cyclic GMP in two human T cell lines, CEM and MOLT-4. In contrast, the closely related polypeptide thysplenin, which differs from thymopoietin at position 34, induced intracellular cyclic GMP elevation in MOLT-4 but not in CEM. We synthesized a series of penta- and tetrapeptide analogs of amino acids 32-36 of human thymopoietin and thysplenin, and now show that distinct patterns of activity can be obtained in these small peptides, with selectivity for cyclic GMP elevation in MOLT-4 alone or CEM alone. This suggests that the thymopoietin receptors (TPR) on these two human T cell lines are distinguishable by their differing ligand specificities, and we have termed them alpha TPR and beta TPR for CEM and MOLT-4 receptors, respectively.

Cell Line↗

PubMed1995

Temporal stability of children's cardiovascular (CV) reactivity: role of ethnicity, gender and family history of myocardial infarction.

Cardiovascular responses to three laboratory stressors (i.e., postural change, treadmill exercise, forehead cold) were evaluated in 106 children (72 Whites, 34 Blacks) who varied in family history (FH) of early myocardial infarction (53 positive FH, 53 negative FH). Subjects were evaluated on two occasions separated by one year. In general, regardless of ethnicity, gender or FH, stability of resting blood pressures (BP) and heart rates were comparable to existing data. Resting cardiac output (CO) and total peripheral resistance (TPR) stability estimates were comparable or higher than the BP estimates across groups except for the +FH subjects and males who showed poor stability to one or both parameters. Moderate stability was observed for all parameters in response to forehead cold and low to moderate stability was observed in HR, CO, and TPR postural change reactivity. The only consistent pattern of significant differences in stability estimates involved ethnicity. African-Americans exhibited significantly higher coefficients compared to Whites in TPR at rest and during postural change and forehead cold. Reasons for the low to moderate resting and reactivity stability estimates are discussed.

Black People↗

PubMed1985

Transposon insertion mutagenesis of Pseudomonas aeruginosa with a Tn5 derivative: application to physical mapping of the arc gene cluster.

For insertional mutagenesis of Pseudomonas aeruginosa, a derivative of the kanamycin-resistance (KmR) transposon Tn5 was constructed (Tn5-751) that carried the trimethoprim-resistance (TpR) determinant from plasmid R751 as an additional marker. Double selection for KmR and TpR avoided the isolation of spontaneous aminoglycoside-resistant mutants which occur at high frequencies in P. aeruginosa. As a delivery system for the recombinant transposon, plasmid pME305, a derivative of the broad-host-range plasma RP1, proved effective; pME305 is temperature-sensitive at 43 degrees C for maintenance in Escherichia coli and P. aeruginosa and deleted for IS21 and the KmR and primase genes. In matings with an E. coli donor carrying pME9(= pME305::Tn5-751), transposon insertion mutants of P. aeruginosa PAO were recovered at approx. 5 X 10(-7)/donor at 43 degrees C. Among Tn5-751 insertional mutants 0.9% were auxotrophs. A thr::Tn5-751 mutation near the recA-like locus rec-102 is useful for the construction of recombination-deficient strains. Several arc::Tn5-751 mutants could be isolated that were defective in anaerobic utilization of arginine as an energy source. From three of these mutants the arc gene region was cloned into an E. coli vector plasmid. Since Tn5-751 has a single EcoRI site between the TpR and KmR genes, EcoRI-generated fragments carrying either resistance determinant plus adjacent chromosomal DNA could be selected separately in E. coli. Thus, a restriction map of the arc region was constructed and verified by hybridization experiments. The arc genes were tightly clustered, confirming earlier genetic evidence.

Arginine↗

PubMed1995

A new dhfrVIII trimethoprim-resistance gene, flanked by IS26, whose product is remote from other dihydrofolate reductases in parsimony analysis.

A new plasmid-borne gene, dhfrVIII, encoding high-level trimethoprim resistance (TpR) was found in an intestinal Escherichia coli. It seems to be a widely occurring mediator of TpR. Among 973 examined TpR E. coli, the new resistance gene was found in 13 (1.3%) isolates from Sweden, Finland and Nigeria. The new gene was sequenced and found to code for a dihydrofolate reductase (DHFR) of 169 amino acids (M(r) 19005). The dhfrVIII gene on the studied plasmid pLMO226 was observed to be flanked by IS26 elements. The dhfrVIII gene and a 3' unidentified open reading frame (ORF) seem to be borne on a compound transposon with IS26 at its ends, since the configuration of two IS26 flanking dhfrVIII and the unidentified ORF was conserved among the isolates that were probe-positive for the gene. Phylogeny parsimony analysis showed the dhfrVIII-encoded enzyme to be only remotely related to other known plasmid-mediated, drug-resistant DHFR. Only a few of the latter form well-supported monophyletic groups.

Amino Acid Sequence↗

PubMed2005

Small glutamine-rich tetratricopeptide repeat-containing protein is composed of three structural units with distinct functions.

Previously, we identified the human small glutamine-rich tetratricopeptide repeat-containing protein (SGT) as a co-chaperone. The tetratricopeptide repeat (TPR) domain in SGT is responsible for interacting with Hsc70. In this study, we demonstrated that the TPR domain of SGT also interacted with Hsp90. Moreover, we investigated the functional significance of regions of SGT outside the TPR domain. Evidently, the N-terminal domain of SGT is necessary and sufficient for its self-association; and, SGT may be a dimer elongated in shape. The C-terminal glutamine-rich region has the capacity to interact with short peptide segments composed of consecutive non-polar amino acids. The C-terminal fragment of SGT indeed plays a role in the association of SGT with in vitro translated rat type 1 glucose transporter, an integral membrane protein folded in a non-physiological state. Moreover, in the presence of SGT, the degradation of the transporter in reticulocyte lysates is inhibited. Taking together, SGT can be separated into three structural units with distinct functions.

Animals↗

PubMed2004

Inhibition of iNOS augments cardiovascular action of noradrenaline in streptozotocin-induced diabetes.

OBJECTIVE: The aim was to determine if inducible nitric oxide synthase (iNOS) contributes to depressed cardiovascular function at the acute phase of streptozotocin-induced diabetes. METHODS: Male Wistar rats were injected with streptozotocin [60 mg/kg, intravenously (i.v.)] or the vehicle (0.9% NaCl) and were studied 3 weeks later. RESULTS: The diabetic and control rats had similar mean arterial pressure (MAP) and total peripheral resistance (TPR). Noradrenaline (NA) increased in vivo left ventricular contractility (LV +dP/dt), MAP and TPR in both groups; however, the responses were markedly less in the diabetic than control rats. Acute administration of 1400W (selective inhibitor of iNOS; 3 mg/kg followed by 3 mg/kg/h, i.v.) did not alter responses to NA in the control rats, but augmented the influence of NA on MAP, TPR and LV +dP/dt in the diabetic rats. At this time, reverse transcription-polymerase chain reaction (RT-PCR) products (RNA) of iNOS were present in the hearts of the diabetic but not control rats. The activity of iNOS was threefold higher in the hearts of the diabetic rats relative to the controls, and the increase was inhibited by 1400W. Furthermore, immunostaining (proteins) of iNOS and nitrotyrosine (NT; marker of peroxynitrite) were identified in the hearts of the diabetic but not control rats. In contrast, the RT-PCR products of eNOS, activity of eNOS and immunostaining of eNOS were of similar intensity in the hearts of both groups. CONCLUSIONS: Activation of iNOS contributes to depressed cardiovascular contractile function to NA at the acute phase of streptozotocin-induced diabetes. Selective inhibition of iNOS partially restored cardiovascular responses to NA.

Acute Disease↗

PubMed2005

Ghrelin improves tissue perfusion in severe sepsis via downregulation of endothelin-1.

OBJECTIVES: Severe sepsis is associated with increased total peripheral resistance (TPR) and decreased organ blood flow, in which endothelin-1 (ET-1) plays an important role. Plasma levels of ghrelin, a newly-identified endogenous ligand for growth hormone secretagogue receptor and a potent vasodilatory peptide, are significantly reduced in sepsis. Ghrelin downregulation heralds the hypodynamic response in severe sepsis. Therefore, we hypothesized that the administration of exogenous ghrelin improves organ blood flow by downregulation of ET-1 under such conditions. METHODS: Male adult Sprague-Dawley rats were subjected to sepsis by cecal ligation and puncture (CLP). At 5 h post-CLP, a bolus intravenous injection of 2 nmol ghrelin was followed by a continuous infusion of 12 nmol ghrelin via a primed mini-pump over 15 h. At 20 h post-CLP (i.e., severe sepsis), cardiac output (CO), stroke volume (SV), TPR, and organ blood flow were measured using (141)Ce-microspheres. Plasma ET-1 levels and preproET-1 gene expression in the liver, small intestine, and kidneys were measured by ELISA and RT-PCR, respectively. The direct effect of ghrelin on ET-1 production was studied using cultured human umbilical vein endothelial cells (HUVECs) treated with tumor necrosis factor-alpha (TNF-alpha). RESULTS: Ghrelin administration reduced TPR, increased CO, SV, and organ blood flow, downregulated preproET-1 gene expression, and decreased plasma levels of ET-1 in sepsis. Ghrelin inhibited TNF-alpha-induced ET-1 release from HUVECs in a dose-dependent manner. Moreover, ghrelin inhibited TNF-alpha-induced activation of nuclear factor-kappaB (NF-kappaB) in HUVECs. CONCLUSIONS: The improvement of tissue perfusion by ghrelin in severe sepsis appears to be mediated by downregulation of ET-1 involving a NF-kappaB-dependent pathway.

Acute Disease↗

PubMed2006

Involvement of some large immunophilins and their ligands in the protection and regeneration of neurons: a hypothetical mode of action.

The powerful immunosuppressive drugs such as FK506 and its derivatives induce some regeneration and protection of neurons from ischaemic brain injury and some other neurological disorders. The drugs form complexes with diverse FKBPs but apparently the FKBP52/FK506 complex was shown to be involved in the protection and regeneration of neurons. We used several different sequence attributes in searching diverse genomic databases for similar motifs as those present in the FKBPs. A Fortran library of algorithms (Par_Seq) has been designed and used in searching for the similarity of sequence motifs extracted from the multiple sequence alignments of diverse groups of proteins (query motifs) and the target motifs which are encoded in various genomes. The following sequence attributes were used in the establishment of the degree of convergence between: (A) amino acid (AA) sequence similarity (ID) of the query/target motifs and (B) their: (1) AA composition (AAC); (2) hydrophobicity (HI); (3) Jensen-Shannon entropy; and (4) AA propensity to form a particular secondary structure. The sequence hallmark of two different groups of peptidylprolyl cis/trans isomerases (PPIases), namely tetratricopetide repeat (TPR) motifs, which are present in the heat-shock cyclophilins and in the large FK506-binding proteins (FKBPs) were used to search various genomic databases. The Par_Seq algorithm has revealed that the TPR motifs have similar sequence attributes as a number of hydrophobic sequence segments of functionally unrelated membrane proteins, including some of the TMs from diverse G protein-coupled receptors (GPCRs). It is proposed that binding of the FKBP52/FK506 complex to the membranes via the TPR motifs and its interaction with some membrane proteins could be in part responsible for some neuro-regeneration and neuro-protection of the brain during some ischaemia-induced stresses.

Algorithms↗