Protease inhibitors modulate apoptosis in mesangial cells derived from a mouse model of HIVAN

Mongia, Anil; Bhaskaran, Madhu; Reddy, Krishna; Manjappa, Nagarathna; Baqi, Noosha; Singhal, Pravin C.

doi:10.1111/j.1523-1755.2004.00464.x

Cited by 14 publications

(12 citation statements)

References 46 publications

(43 reference statements)

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“…Morphine has been reported to cause kidney cell injury in both in vitro and in vivo studies [7], [8], [9], [10], [11], [12]. In the current study, we observed that administration of morphine contributed to albuminuria which appeared to be glomerular in origin and a consequence of the loss of slit diaphragm integrity [27].…”

Section: Discussionsupporting

confidence: 56%

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Morphine Induces Albuminuria by Compromising Podocyte Integrity

et al. 2013

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Morphine has been reported to accelerate the progression of chronic kidney disease. However, whether morphine affects slit diaphragm (SD), the major constituent of glomerular filtration barrier, is still unclear. In the present study, we examined the effect of morphine on glomerular filtration barrier in general and podocyte integrity in particular. Mice were administered either normal saline or morphine for 72 h, then urine samples were collected and kidneys were subsequently isolated for immunohistochemical studies and Western blot. For in vitro studies, human podocytes were treated with morphine and then probed for the molecular markers of slit diaphragm. Morphine-receiving mice displayed a significant increase in albuminuria and showed effacement of podocyte foot processes. In both in vivo and in vitro studies, the expression of synaptopodin, a molecular marker for podocyte integrity, and the slit diaphragm constituting molecules (SDCM), such as nephrin, podocin, and CD2-associated protein (CD2AP), were decreased in morphine-treated podocytes. In vitro studies indicated that morphine modulated podocyte expression of SDCM through opiate mu (MOR) and kappa (KOR) receptors. Since morphine also enhanced podocyte oxidative stress, the latter seems to contribute to decreased SDCM expression. In addition, AKT, p38, and JNK pathways were involved in morphine-induced down regulation of SDCM in human podocytes. These findings demonstrate that morphine has the potential to alter the glomerular filtration barrier by compromising the integrity of podocytes.

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Section: Discussionsupporting

confidence: 56%

“…Morphine has been reported to exert a bimodal effect on the growth of kidney fibroblasts and glomerular mesangial cells [6], [7], [8], [9], [10]. Intravenous opiate addiction has also been considered a risk factor for the development of human immunodeficiency (HIV)-associated nephropathy [11], [12].…”

Section: Introductionmentioning

confidence: 99%

Morphine Induces Albuminuria by Compromising Podocyte Integrity

et al. 2013

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“…In an accompanying article in this issue of Kidney International Mongia et al [1] demonstrate viral-independent antiapoptotic and ROS-scavenging effects of PIs on mouse mesangial cells in vitro. This protection extends to the exaggerated mesangial apoptosis induced by HIV gene expression and recreational drug metabolites.…”

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confidence: 98%

“…The basis of this protection is complex, as both HIV reverse-transcriptase inhibitors and HIV protease inhibitors (PIs) have biologic actions independent of their antiviral effects. A new study by Mongia et al [1] in this issue of Kidney International shows that the PI saquinavir significantly blocks reactive oxygen species (ROS) generation and ROS-linked apoptosis in mouse mesangial cells independent of HIV gene expression. Thus, HAART modulation of renal injury may transcend its antiviral effects.…”

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confidence: 99%

Taking HAART in HIVAN: Will protease inhibitor sparing regimens alter renal outcome?

Foster

2004

Kidney International

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“…Interestingly, mesangial cells harvested from HIV-1 transgenic mice showed both accelerated rate of proliferation as well as of apoptosis [38]. Since antioxidants were able to inhibit these growth characteristics of mesangial cells, these pro-mitogenic and pro-apoptotic effects of the HIV-1 transgene were attributed to the levels of ongoing oxidative stress [38]. …”

Section: Hiv-1 Proteins Have a Bimodal Growth Effect On Mesangial Cellsmentioning

confidence: 99%

HIV-1 and Kidney Cells: Better Understanding of Viral Interaction

Mikulak

Singhal²

2010

Nephron Exp Nephrol

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HIV-associated nephropathy (HIVAN) is the most common disease affecting untreated seropositive patients of African descent. Besides genetic (African descent) and HIV-1 infection (environmental), specific host factors such as activation of renin-angiotensin-aldosterone system (RAAS) have also been demonstrated to play a role in the manifestation of HIVAN. The recent identification of MYH9 as susceptible allele is a key step forward in our understanding for the pathogenesis of focal glomerulosclerosis in people of African-American descent. HIV-1 transgenic models have significantly advanced our knowledge base in terms of role of HIV-1 genes in general and individual gene in particular in the development of renal lesions mimicking HIVAN. These studies suggest that viral replication is not needed for the development of renal lesions. Renal biopsy data from HIVAN patients suggest that renal epithelial cells express HIV-1 genes and thus it may be sufficient to invoke HIVAN phenotype in the presence of specific host and genetic factors. On the other hand, immune response to infection may be required to induce HIV-1 associated immune complex kidney disease (HIVICK). Since renal cell lack conventional HIV-1 receptors, HIV-1 entry into renal cells has been a mystery. Recently, non-conventional pathways have been demonstrated to facilitate HIV-1 entry into renal cells in in vitro studies. These include presence of DEC-205 receptors in renal tubular cells and lipid rafts in podocytes. However, HIV-1 entry through these pathways only allows non-productive infection. It appears that the presence of specific genetic and host factors in in vivo conditions may be facilitating the development of the productive HIV-1 infection in kidney cells.

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Protease inhibitors modulate apoptosis in mesangial cells derived from a mouse model of HIVAN

Abstract: Oxidative stress seems to play a role in the accelerated rate of HTrMC apoptosis both under basal and MSS. Saquinavir may be inhibiting HTrMC apoptosis by mitigating oxidative stress.

Cited by 14 publications

References 46 publications

Morphine Induces Albuminuria by Compromising Podocyte Integrity

Morphine Induces Albuminuria by Compromising Podocyte Integrity

Taking HAART in HIVAN: Will protease inhibitor sparing regimens alter renal outcome?

HIV-1 and Kidney Cells: Better Understanding of Viral Interaction

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