In vivo and in vitro modulation of MDR molecules in murine thymocytes

Leite, Daniela Ferraz Pereira; Echevarria-Lima, Juliana; Salgado, Leonardo T.; Capella, Marcia A. M.; Calixto, João B.; Rumjanek, Vivian M.

doi:10.1016/j.intimp.2005.08.005

Cited by 13 publications

(21 citation statements)

References 46 publications

(59 reference statements)

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“…Therefore, the present study tested whether a single in vivo administration of ouabain could result in alterations in ABCB1 protein expression in lymph nodes and thymi. ABCB1 activity is only observed in 5-10% of thymocytes, as it is restricted to the most immature subset, the double negative cluster of differentiation (CD)4 -/CD8 -subpopulation, and to the fully mature subset, the CD4 + and CD8 + T cells (23). Therefore, the number of cells presenting ABCB1 activity in the thymus was determined by the percentage of cells with low Rho content, which were modulated by the ABCB1 inhibitor cyclosporin A (CsA) (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…ABCB1 is associated with the transport of several substrates, including lipids, hormones and cytokines (19,49,50). In thymocytes, the expression of this protein is restricted to the double negative (CD4 -/CD8 -) thymocytes and to the simple positive populations CD4 + and CD8 + , representing the most immature subset and the mature thymocyte populations, respectively (23). Thus, the observation that ouabain induced a significant decrease in the percentage of thymocytes with ABCB1 activity raises at least three hypotheses: i) That thymocytes with ABCB1 are simply undergoing protein downregulation in the plasma membrane; ii) that thymocyte maturation is being impaired, leading to an accumulation of double positive cells (CD4 + /CD8 + ), which do not exhibit ABCB1 activity; or iii) that the thymocytes with decreased ABCB1 activity after the ouabain injection could be undergoing apoptosis.…”

Section: Discussionmentioning

confidence: 99%

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Ouabain-induced alterations in ABCB1 of mesenteric lymph nodes and thymocytes of rats and mice

2016

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Abstract. Ouabain is a glycoside with immunomodulating properties, and recent studies have suggested its use in adjuvant therapy for cancer treatment. Ouabain is known to modulate the immune system in vitro, and previous studies have revealed that ouabain can modulate the expression and activity of ABCB1, a protein associated with multidrug resistance present in immune system. Therefore, the present study investigated alterations in the expression and activity of ABCB1 in the thymi, peripheral blood monocytes and lymph nodes of Wistar rats and Swiss mice treated acutely or chronically with ouabain. A decrease of almost 45% in the monocyte count and an increase of 55% in the basophil count were observed. A significant decrease (75% reduction) in the amount of cells with ABCB1 activity was found in the thymocytes of ouabain-treated rats and mice. The possible implications of these results for cancer treatment are discussed.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ouabain-induced alterations in ABCB1 of mesenteric lymph nodes and thymocytes of rats and mice

2016

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“…36 Other than its important role in the secretion of glutathione and lipid mediators, other important actions have been assigned for ABCC1 function in the immune system, eg, dendritic cell differentiation and thymocyte maturation. [37][38][39] The third MDR-related protein, ABCG2, is expressed in the apical membrane of several organs, including the kidney and brain. It is highly expressed in the gastrointestinal tract and liver 40,41 (Figure).…”

Section: Physiological Roles Of Mdr-related Proteinsmentioning

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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“…in a final volume of 5 l/g, as described before [15]. One hour later, mice were sacrificed, and peritoneal cells were recovered, washed, and put on ice until analysis by flow cytometry.…”

Section: Abcc Activity In Vivomentioning

confidence: 99%