Female Protein Levels Research Articles

Reduced PIN1 expression in neocortical and limbic brain regions in female Alzheimer’s patients correlates with cognitive and neuropathological phenotypes

Women have a higher incidence of Alzheimer’s disease (AD), even after adjusting for increased longevity. Thus, there is an urgent need to identify genes that underpin sex-associated risk of AD. PIN1 is a key regulator of the tau phosphorylation signaling pathway; however, potential differences in PIN1 expression, in males and females, are still unknown. We analyzed brain transcriptomic datasets focusing on sex differences in PIN1 mRNA levels in an aging and AD cohort, which revealed reduced PIN1 levels primarily within females. We validated this observation in an independent dataset (ROS/MAP), which also revealed that PIN1 is negatively correlated with multiregional neurofibrillary tangle density and global cognitive function in females only. Additional analysis revealed a decrease in PIN1 in subjects with mild cognitive impairment (MCI) compared with aged individuals, again driven predominantly by female subjects. Histochemical analysis of PIN1 in AD and control male and female neocortex revealed an overall decrease in axonal PIN1 protein levels in females. These findings emphasize the importance of considering sex differences in AD research.

Conditional, inducible gene silencing in dopamine neurons reveals a sex-specific role for Rit2 GTPase in acute cocaine response and striatal function.

Dopamine (DA) signaling is critical for movement, motivation, and addictive behavior. The neuronal GTPase, Rit2, is enriched in DA neurons (DANs), binds directly to the DA transporter (DAT), and is implicated in several DA-related neuropsychiatric disorders. However, it remains unknown whether Rit2 plays a role in either DAergic signaling and/or DA-dependent behaviors. Here we leveraged the TET-OFF system to conditionally silence Rit2 in Pitx3IRES2-tTA mouse DANs. Following DAergic Rit2 knockdown (Rit2-KD), mice displayed an anxiolytic phenotype, with no change in baseline locomotion. Further, males exhibited increased acute cocaine sensitivity, whereas DAergic Rit2-KD suppressed acute cocaine sensitivity in females. DAergic Rit2-KD did not affect presynaptic TH and DAT protein levels in females, nor was TH was affected in males; however, DAT was significantly diminished in males. Paradoxically, despite decreased DAT levels in males, striatal DA uptake was enhanced, but was not due to enhanced DAT surface expression in either dorsal or ventral striatum. Finally, patch recordings in nucleus accumbens (NAcc) medium spiny neurons (MSNs) revealed reciprocal changes in spontaneous EPSP (sEPSP) frequency in male and female D1+ and D2+ MSNs following DAergic Rit2-KD. In males, sEPSP frequency was decreased in D1+, but not D2+, MSNs, whereas in females sEPSP frequency decreased in D2+, but not D1+, MSNs. Moreover, DAergic Rit2-KD abolished the ability of cocaine to reduce sEPSP frequency in D1+, but not D2+, male MSNs. Taken together, our studies are among the first to acheive AAV-mediated, conditional and inducible DAergic knockdown in vivo. Importantly, our results provide the first evidence that DAergic Rit2 expression differentially impacts striatal function and DA-dependent behaviors in males and females.

Seasonal and Sexual Variation of the Intermediate Metabolism and Body Condition Indexes in the LizardTropidurus catalanensis(Gudynas and Skuk, 1983) (Squamata: Tropiduridae)

Throughout the life cycle of organisms, nutrient intake is necessary for the maintenance of the functions of daily life and in preparation for a variety of biological events, such as molting, migration, hibernation, and reproduction. One of the most energetically costly events is reproduction. Present study sought to elucidate the seasonal variations in the markers of intermediate metabolism (total proteins, uric acid, glucose, total lipids, triglycerides, total cholesterol, VLDL cholesterol, and glycogen) and body condition indices (gonadossomatic, hepatosomatic, and abdominal fat index) in Tropidurus catalanensis, in order to know the physiological costs of reproduction in this species, also allowing these parameters to be used as markers in studies of environmental alterations. During the study period, 38 males and 35 females were collected. Tropidurus catalanensis is a lizard that inhabits the Pampa grasslands, a biome that stretches across Argentina, Brazil, and Uruguay. Results obtained reveal that this lizard exhibits a clear pattern of seasonal variation in its metabolism, as reflected mainly in levels of plasma total protein, liver glycogen, total lipids, and triglycerides in males and females; and in blood glucose and lipid, and liver protein levels in females. It bears stressing that all body condition indices analyzed varied over the course of the year. The parameters studied can be used to evaluate the impact of changes in environmental conditions on these animals. Winter months appear to trigger a reduction in overall metabolism, most intensely in males. Reproductive period seems to be the biological event that demands greater energy demand, leading to the mobilization of energy stocks mainly in females, where the search for food may be reduced in the months of reproductive peak (spring). The response pattern observed during the reproductive period suggests that this time represents a critical point in terms of the animal's adaptation to its life cycle.

Serum and saliva protein levels in females with breast cancer.

The aim of the present study was to investigate the change in the total protein content between the serum and saliva of female patients with breast cancer and in healthy females. The study was conducted between October 2012 and November 2013. There were 80 females in the present study with 40 breast cancer patients and 40 healthy control subjects, with an age range of 50–70 years. The results of the study showed that the mean value ± standard deviation of the total serum protein in patients with breast cancer was 7.63±0.41 g/dl, whereas in the healthy subjects it was 6.14±1.84 g/dl. The total salivary protein measurement was 0.14±0.07 g/dl and 0.25±0.09 g/dl in the breast cancer and healthy group, respectively. Therefore, it can be concluded that the total serum protein was higher in female patients with breast cancer, whereas the levels in the saliva were lower compared to the healthy female group. The results of the present study indicate that serum protein levels may be used for the diagnosis of breast cancer.

Four-week oral toxicity studies of the new quinolone antibacterial agent cetefloxacin tosylate in rats and marmoset monkeys.

Four-week oral toxicity studies with cetefloxacin tosylate ((-)-7[3-(R)-amino-2-(S)-methyl-1-azetidinyl]-1-(2,4- difluorophenyl)-1,4-dihydro-6-fluoro-4-oxo-3-quinolinecarboxylic acid tosylate, CAS 141725-88-4 (base), E-4868.Ts) a new quinolone antibacterial agent, were performed in Sprague-Dawley rats and marmoset monkeys at doses of 100, 450, 2000 mg/kg/d and 25, 50, 125, 300 mg/kg/d, respectively. In rats, due to its toxicity the high dose was decreased to 1000 mg/kg/d after 3 days of treatment. Mortality was recorded among high dose rats receiving 2000 or 1000 mg/kg/d. Rats receiving dosages of 450 or 2000/1000 mg/kg/d showed less activated mandibular lymph nodes, cortical lymphocyte depletion of mandibular and/or mesenteric lymph nodes, atrophy of the white pulp of the spleen, cortical atrophy of thymus and thymic apoptosis. Enlarged caeca, increased water consumption and variations in plasma electrolyte levels were observed in animals receiving these dosages and in male rats receiving 100 mg/kg/d. Low neutrophil counts were observed in rats receiving dosages of 100 or 450 mg/kg/d, and increased alkaline phosphatase and alanine transaminase plasma levels and slightly decreased plasma protein levels in females receiving 450 or 2000/1000 mg/kg/d. Marmosets receiving dosages of 50 mg/kg/d and above displayed several clinical signs which included emesis, diarrhoea, ptosis, occasional episodes of under- and overactivity, and excessive scratching activity. Skin reddening was observed during the first week of treatment in marmosets receiving 300 mg/kg/d. On the basis of the results obtained it can be concluded that the non-toxic doses of E-4868. Ts after 4-week oral administration in rats and marmoset monkeys were 100 and 25 mg/kg/d, respectively.

Sex dependent differences in collecting duct renin during high salt intake

Collecting duct (CD) renin is upregulated during Ang II‐dependent hypertension. In this study we examined if CD renin exhibits sex differences during changes in salt intake in 19 Sprague‐Dawley rats distributed in 4 groups [1) Controls male (n=5); 2) Controls female (n=5); HS male (n=5); and HS female (n=4) fed a normal and HS diet (8% NaCl). Baseline systolic blood pressure (SBP) was not different between males and female rats (males: 116±3 vs. female: 119±2 mmHg) nor after 2‐weeks fed a HS diet (male 126±2 vs. female: 128±2 mmHg). Although renin mRNA and protein levels examined by qRT‐PCR and Western blot in renal medullary tissues were similar in male and female rats under control conditions [Controls male: mRNA= 1.0±0.4 AU; protein=1.0±0.1 DU vs. Controls female: mRNA=0.3±0.1AU; protein=0.8±0.1 DU)]; HS diet intake significantly increased the CD renin transcript and protein levels in females but not in male rats [mRNA=(HS male: 1.5±0.1 vs. HS female: 3.4±0.6 AU); protein= (HS male: 1.0±0.3 DU vs. HS female: 1.8 ±0.7 DU). These data suggest that although there is not sex difference in CD renin gene expression under basal conditions, HS intake appears to stimulate renin in distal nephron segment only in female rats. Future studies are planned to determine whether HS intake during chronic Ang II infusion leads to sexual dimorphisms of blood pressure during Ang II‐dependent hypertension.

Annual reproductive phase-related profile of sex steroids and their carrier, SHBG, in the Indian major carp, Labeo rohita

This study reports annual cyclic changes in the plasma levels of sex hormone binding globulin (SHBG), sex steroids (E 2, estradiol; T, testosterone; P, progesterone) and protein (PRT) in correlation with reproductive phases in both sexes of an Indian major carp, Labeo rohita. Plasma SHBG, E 2, T and PRT levels in females and SHBG and T levels in males showed steady increases ( p < 0.005) in parallel with the gonadosomatic index (GSI) escalation in the preparatory and prespawning phases attaining peak levels before spawning. During the late spawning and early postspawning phases, E 2, T and SHBG levels revealed an abrupt and significant descent coincident with the GSI in both the sexes. The plasma P levels in females, attaining measurable quantities only in prespawning phase, underwent a rapid increase followed by a quick decline to undetectable levels in the spawning phase. This occurrence of P for a short duration suggests a limited role in ovarian function. During the resting phase, the E 2, T and SHBG levels in both sexes declined to minimum in conjunction with a decrease in the GSI, while PRT showed an increase. These data suggest that a significant increase in SHBG ( p < 0.005) prior to spawning enhances its binding capacity with sex steroids in both sexes synchronizing the reproductive activity. The significant increase of PRT in females during early spawning reflects its role in oocyte function, while PRT and E 2 in males may not significantly affect the testicular activity.

Total plasma protein level as an indicator of condition in wild American kestrels (Falco sparverius)

Total plasma protein levels were determined for 292 female and 228 male American kestrels (Falco sparverius) in the wild. Plasma protein levels were significantly higher in females than in males, and higher during prelaying than during incubation. For both sexes, plasma protein levels did not vary significantly with the number of days before or after egg laying on which the sample was taken, time of sampling, prey abundance, age, molt, or infection by the blood parasite Haemoproteus sp. Protein levels in females increased with date of sampling and body condition during prelaying, while the same pattern was seen in males during incubation. With the exception of those of prelaying females, plasma protein levels increased with ambient temperature. The results of this study suggest that at least some of the variation observed in total protein levels is attributable to physical condition. However, further investigation is required before the reliability of using total plasma protein level as a tool to assess the health and condition of kestrels is known.

Purification and immunochemical characterization of a rat liver sulphotransferase conjugating paracetamol

Paracetamol sulphotransferase (ST) was purified 250-fold from male rat liver, and the pure enzyme used to elicit antibodies in rabbit. The enzyme was active towards paracetamol at pH 9.0, as well as towards several commonly used drugs, and formed sulphates at both O- and N-atoms. Comparison of the substrate specificity of paracetamol ST with that of aryl sulphotransferases isolated by other workers suggested that we have purified a previously unknown isoenzyme of rat liver ST, although the difficulties of characterization of STs based on their substrate specificities is noted. The antibody preparation recognized only one polypeptide ( M r = 35,000) on immunoblot analysis of rabbit liver cytosol, corresponding to purified paracetamol ST. Analysis of the tissue distribution of this protein demonstrated that its expression was restricted to the liver, as was the enzyme activity. The observed sex difference in paracetamol ST (males > females) was determined by immunoblot analysis to be the result of reduced enzyme protein levels in females. In human liver cytosol, the antibody recognized two polypeptides, probably corresponding to M- and P-phenol STs, suggesting significant sequence similarity between rat and human phenol sulphotransferases.

Tamoxifen inhibits estrogen-induced hepatic injury in hamsters.

Estrogens have an unusual toxic effect on the liver of two hamster species, the Armenian and the Chinese hamster. The hepatotoxicity was detectable clinically by hyperbilirubinemia and confirmed histologically by the presence of hepatic degenerative-regenerative changes. Administration of tamoxifen with estrogen [either ethynyl estradiol or diethylstilbestrol (DES)] completely abrogated the hepatotoxic effects, suggesting that estrogen receptor (ER) was necessary for estrogen to damage liver. In Armenian hamsters, estrogens decreased hepatic synthesis of female protein (FP); tamoxifen also abolished this DES effect and resulted in a net increase in serum FP levels. DES administration produced higher serum bilirubin levels and lower serum FP levels in females than in males. Paradoxically, tamoxifen blocked these DES effects more effectively and efficiently in females than in males. Estrogens did not injure uteri of Armenian and Chinese hamsters and were nontoxic to livers of other hamsters species, such as Syrian and Turkish. This model provides another perspective of the acute cellular derangement that can be effected by estrogen-ER complex and may indicate a yet unknown mode of ER action.

Hamster female protein. A divergent acute phase protein in male and female Syrian hamsters.

Normal adult male hamsters have low levels (10-20 micrograms) of female protein (FP) in serum which increase approximately fivefold during an acute phase response. In contrast, normal females have 50- to 100-fold higher serum levels and the acute phase reaction consists of a transient decrease in FP (approximately 50%), followed by a return to normal levels even under adverse conditions such as cortisone treatment (which by itself has a depressing effect on FP levels in normal females). The acute phase response was not inherently associated with gender, as the pattern of response could be changed to that of the opposite sex by appropriate hormonal manipulation. That is, castrated or diethylstilbestrol-treated males with high FP levels showed a female-type response whereas testosterone-treated females with low FP levels showed a male-type response. Studies on catabolism of 125I-FP showed a similar rapid half-life (T1/2, 9-16 h) in normal males and females and indicated that the sex difference in serum concentration was due to greater synthesis of FP in females. The divergent acute phase reaction of serum FP was related directly to changes in the FP synthetic rate (increased in males, decreased in females). As an indicator of serious pathology, a decrease of FP to very low levels in females was associated frequently with impending death.