Modulation of the mdr-1b gene in the kidney of rats subjected to dehydration or a high-salt diet

Morales, M.M.; Capella, Marcia A. M.; Sanches, M.V.; Lopes, A.G.; Guggino, W.B.

doi:10.1007/s004240050950

Cited by 8 publications

(8 citation statements)

References 25 publications

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“…One possible reason for such variability is that the ABCB1 gene is polymorphic, and two of its single-nucleotide polymorphisms (SNPs), rs1128503 and rs1045642, may modify the final protein conformation, compromising its membrane stability and substrate recognition 7,8. Finally, it has been reported that the ABCB1 expression may also be modulated by plasma aldosterone9 or cortisol,10 as well as by dietary salt and dehydration 9…”

Section: Introductionmentioning

confidence: 99%

Loss of constitutive <em>ABCB1</em> expression in breast cancer associated with worse prognosis

Delou¹,

Vignal²,

Indio-do-Brasil³

et al. 2017

BCTT

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ABCB1 gene encodes an adenosine 5′-triphosphate–binding cassette transporter, which not only confers multidrug resistance phenotype in malignant cells, but is also present in several nonmalignant tissues. For the last thirty years, ABCB1 expression in breast cancer has been described by many authors, but the extent of expression differs among the studies, and there is no consensus regarding its potential role in carcinogenesis or in the tumor response to antineoplastic drugs. This study aimed to characterize the expression of ABCB1 in breast tumors as a function of genetic, clinical, and histopathological variables. The ABCB1 expression was also evaluated in nonmalignant mammary tissues adjacent to tumors and in benign lesions. The detection of ABCB1 protein was performed by immunohistochemistry in tissue specimens of excised breasts obtained from a prospective cohort of Brazilian women with breast cancer. The association of ABCB1 protein levels with ABCB1 mRNA, gene polymorphisms, and clinical and histopathological variables was also evaluated. The Kaplan–Meier curves and multivariate Cox regression analyses were conducted to identify independent predictors of disease-free survival of patients with breast cancer. ABCB1 was detected in 86.3% (656) of breast tumors, 98.8% (606) of nonmalignant mammary tissue adjacent to tumors, and 100% (28) of benign lesions. Reduced ABCB1 protein levels in breast tumors was associated with triple-negative subtype (adjusted odds ratio [ORadj] =0.24; 95% confidence interval [CI] =0.13–0.45), lymph node status < pN2 (ORadj =0.27; 95% CI =0.10–0.71), tumor size >2 cm (ORadj =0.55; 95% CI =0.32–0.93), and hypertensive status (ORadj =0.42; 95% CI =0.24–0.73), and it was significantly associated with shorter disease-free survival, either for all breast cancer patients (p log-rank =0.012; hazard ratio [HR] =3.46; 95% CI =1.21–9.91) or for those with triple-negative tumors (p log-rank =0.007; HR =11.41; 95% CI =1.29–100.67). The loss of constitutive ABCB1 expression in breast cancer, especially in triple-negative tumors, seems to indicate a subgroup of worse prognosis.

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Section: Introductionmentioning

confidence: 99%

Loss of constitutive <em>ABCB1</em> expression in breast cancer associated with worse prognosis

Delou¹,

Vignal²,

Indio-do-Brasil³

et al. 2017

BCTT

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“…However, the experimental conditions did not allow the distinction between the highly similar sequences of mdr1 and mdr3. Morales et al (2000) demonstrated that in renal tubular cells the mdr1 isoform activity can be modulated by aldosterone.…”

Section: Introductionmentioning

confidence: 99%

Expression of mdr isoforms in mice during estrous cycle and under hormone stimulation

et al. 2006

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The multidrug resistance (MDR) phenotype is associated with the expression of P-glycoprotein (Pgp), coded by the multigenic mdr family. Mice present the isoforms mdr1 and mdr3, which are responsible for multidrug resistance, and mdr2, that is involved in the transport of phospholipids. mdr1 expression has more recently been associated also with the secretion of steroid hormones. This work presents an RT-PCR analysis of the expression of mdr isoforms, in several organs of mice during different phases of the estrous cycle. Additionally, females were ovariectomized, submitted to different hormone treatments, and their uterus was analyzed for the expression of mdr isoforms. The results show that in the adrenal gland and ovaries mdr1 is the main isoform during proestrus, and that progesterone or a combination of progesterone and estrogen induce the expression of all mdr isoforms in the uterus of ovariectomized females. We suggest that the functions of mdr1 and mdr3 are overlapping, that mdr3 may be the more efficient isoform in the detoxification function, and that mdr1 may be more closely related to the secretion of steroid hormones.

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“…59 In addition to the fact that a high-salt diet alters the expression of ABCB1 in rats, we also showed that the mRNA expression of ABCB1 was diminished in adrenalectomized rats, suggesting that aldosterone could be an endogenous regulator of this protein. 56 More recently, it was shown that aldosterone activity in the plasma, brain, and heart was significantly higher in ABCB1-deficient mice. 60 The data obtained in the above studies, performed in different animal models, pointed to a possible role for ABCB1 in hypertension and were followed by additional studies in humans.…”

Section: Evidence For the Interplay Between Abcb1 And Hypertension: Rmentioning

confidence: 99%

“…56 In addition, in a recent study, we showed that ABCB1, but not ABCC1, is downregulated in peripheral blood mononuclear cells and in the kidneys of spontaneously hypertensive rats. 57 Our results were confirmed by a study of another group showing that a high-salt diet reduced the expression levels of the abcb1a and abcb1b genes in the rat liver and kidney but increased their expression levels in the duodenum, jejunum, and ileum, suggesting that the regulation of this protein is tissue specific.…”

Section: Evidence For the Interplay Between Abcb1 And Hypertension: Rmentioning

confidence: 99%

Unveiling the Role of Multidrug Resistance Proteins in Hypertension

2009

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H ypertension is a chronic condition associated with an increased risk of mortality and morbidity. It is estimated to cause 4.5% of current global disease burden, and its prevalence is similar in both developing and developed countries. 1 According to a recent review, Ϸ54% of stroke, 47% of ischemic heart disease, 75% of hypertensive disease, and 25% of other cardiovascular disease worldwide can be attributable to high blood pressure. 2 Altered levels of angiotensin and aldosterone are common findings in hypertension. Aldosterone has been shown to play an important role in the pathophysiology of numerous cardiovascular disorders, including heart failure and hypertension, 3 and the renin-angiotensin-aldosterone system is currently an important target for 5 antihypertensive drug classes: ␤-blockers, renin inhibitors, angiotensin-conversion enzyme inhibitors, angiotensin receptor blockers, and aldosterone antagonists. 4 In the last few years, increasing evidence has pointed to an involvement of multidrug resistance (MDR)-related proteins with hypertension. Both ABCB1 (P-glycoprotein) and ABCC1 (MDR-associated protein 1), the 2 main proteins first described in multidrug-resistant tumors, are known to physiologically transport several endobiotics, including hormones. 5,6 Moreover, ABCB1 and ABCG2 (the third protein related to MDR), seem to also be related to the secretion of several drugs to urine, including some antihypertensives. 7,8 This review summarizes the recent findings regarding the relationship between MDR-related proteins and hypertension. ABC Superfamily and MDR in CancerMDR is still the main cause of failure in cancer chemotherapy. Although it is a multifactorial phenomenon, virtually all MDR cells present an ATP-dependent reduction in intracellular drug accumulation because of the overexpression of Ն1 of 3 proteins belonging to the ATP-binding cassette (ABC) family of transporters. 9,10 The ABC superfamily is one of the largest protein families, and its members have been found in virtually all organisms examined up to now. It is consisted of 7 subfamilies, ABCA, ABCB, ABCC, ABCD, ABCE, ABCF, and ABCG, in which each protein receives a number, eg, ABCA1, ABCC7, or ABCG2. The majority of the ABC proteins are membrane transporters that actively translocate a wide range of substrates to various cellular compartments using ATP hydrolysis, which may explain the many functions fulfilled by these proteins in different organisms.The first ABC protein related to MDR was initially named P-glycoprotein and subsequently MDR1, with P being a reference for an apparent altered membrane permeability conferred by its overexpression. 11 This protein is now called ABCB1, meaning that it is the first member of the B subgroup of the ABC superfamily. The second MDR-related protein was discovered 16 years later and was called MDRassociated protein, 12 or MDR-associated protein 1, and is now renamed ABCC1. The third important MDR-related protein, now called ABCG2, was discovered almost simultaneously by 3 distinct groups, receiv...

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Modulation of the mdr-1b gene in the kidney of rats subjected to dehydration or a high-salt diet

Cited by 8 publications

References 25 publications

Loss of constitutive <em>ABCB1</em> expression in breast cancer associated with worse prognosis

Loss of constitutive <em>ABCB1</em> expression in breast cancer associated with worse prognosis

Expression of mdr isoforms in mice during estrous cycle and under hormone stimulation

Unveiling the Role of Multidrug Resistance Proteins in Hypertension

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