Ritonavir Inhibits NF-AT Activation Through Effects on the PI-3 Kinase/Akt Pathway

Pati, Shibani; Nguyen, AnhThu; Foulke, James S.; Weichold, Frank F.; Reitz, Marvin S.

doi:10.1186/1742-4690-2-s1-s44

Cited by 2 publications

(1 citation statement)

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“…These proteasomes are involved in the degradation of the IB family inhibitory molecules that sequester NF-B transcription factors in the cytosol in resting conditions, masking their nuclear location necessary for gene transcription (Palombella et al, 1994). It can be speculated, according to some recent works (Gaedicke et al, 2002;Pati et al, 2002), that HIV-PIs reduced proteasome activities in our model, decreasing NF-B translocation and MMP-9 gene transcription. This hypothesis is currently being investigated by our group.…”

Section: Mmp-9 Involvement In Human Adipocyte Differentiation 1277mentioning

confidence: 64%

Protease Inhibitor Treatments Reveal Specific Involvement of Matrix Metalloproteinase-9 in Human Adipocyte Differentiation

Bourlier¹,

Zakaroff-Girard²,

Barros³

et al. 2004

J Pharmacol Exp Ther

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We previously showed that human and murine 3T3-F442A preadipocytes produced and released matrix metalloproteinases (MMPs) 2 and 9 and that a treatment by MMP inhibitors resulted in the blockade of murine fat cell adipose conversion. In parallel, investigators reported that other protease inhibitors, the human immunodeficiency virus (HIV) protease inhibitors (PIs) involved in lipodystrophy in humans, also reduced the adipocyte differentiation process of several murine cell lines. The present work was performed to define the effects of MMP inhibitors and HIV-PIs on the human adipocyte differentiation process, to clarify the involvement of MMPs in the control of human adipogenesis, and to determine whether HIV-PIs interact with MMPs in the control of this process. The effect of two MMP inhibitor and four HIV-PI treatments on the differentiation of primary culture human preadipocytes, as well as the putative relationships between HIV-PIs and MMP-2 and -9 expression, release, or activity were investigated. We showed that MMP inhibitors and HIV-PIs reduced the human adipocyte differentiation process as assessed by the decrease of cell protein and/or triglyceride contents and expression of fatty acid binding protein and hormone-sensitive lipase, two adipocyte markers. Unlike MMP inhibitors, HIV-PIs were devoid of any effect per se on recombinant MMP-2 and 9 activities but reduced the expression and release of MMP-9 by human preadipocytes. Thus, the present study indicates that the modulation of the extracellular matrix components through the production and/or activity of MMPs, and, more precisely, MMP-9 might be a key factor in the regulation of human adipose tissue development.The mechanisms responsible for the growth of adipose tissue (AT) are still not well defined. Adipocyte hypertrophy and hyperplasia, due to the recruitment and differentiation of adipocyte precursor cells, or preadipocytes, into adipocytes are major cellular events in the development of the fat mass. Together with the hypertrophy and the hyperplasia events, recent investigations have clearly demonstrated that angiogenesis and extracellular matrix (ECM) remodeling are required for coordinated growth of the fat depot (Lijnen et al., 2002;Rupnick et al., 2002). Among the enzymes involved in the degradation of the ECM components, the matrix metalloproteinase (MMP) family is considered to play a major role (Sternlicht and Werb, 2001). In a previous report, we demonstrated that mature human adipocytes and preadipocytes produce and release two members of the MMP family, MMP-2 and -9, the expression and activity of which were shown to be dependent on the adipocyte differentiation process (Bouloumié et al., 2001). Interestingly, we also reported that treatment of the murine 3T3-F442A preadipocytes, which also produced MMP-2 and -9 during adipose conversion, with MMP inhibitors decreased the rate of adipocyte differentiation, suggesting that MMP activities are required for adipogenesis in rodents. However, no data are available concerning the poten...

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Section: Mmp-9 Involvement In Human Adipocyte Differentiation 1277mentioning

confidence: 64%

Protease Inhibitor Treatments Reveal Specific Involvement of Matrix Metalloproteinase-9 in Human Adipocyte Differentiation

Bourlier¹,

Zakaroff-Girard²,

Barros³

et al. 2004

J Pharmacol Exp Ther

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Divulging the Intricacies of Crosstalk Between NF-Kb and Nrf2-Keap1 Pathway in Neurological Complications of COVID-19

et al. 2021

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The severity of COVID-19 infection is surging day by day. With the cases increasing daily, it is becoming more and more essential to understand the pathogenic mechanisms underlying the severity of the disease. It is now well known that the infection manifests itself primarily as respiratory, but the involvement of the other organ systems has now been documented in many studies. SARS-CoV-2 can invade the nervous system by a multitude of proposed mechanisms that have been discussed in this review. NF-κB and Nrf2 are transcription factors that regulate genes responsible for inflammatory and anti-oxidant response respectively. Specific focus in this review has been given to NF-κB and Nrf2 pathways that are involved in the cytokine storm and oxidative stress that are the hallmarks of COVID-19. As the immune injury is an important mechanism of neuro-invasion and neuroinflammation, there is the possible involvement of these two pathways in the neurological complications. The crosstalk mechanisms of these signaling pathways have also been discussed. Immuno-modulators both synthetic and natural are promising candidates in catering to the pathologies targeted in the aforementioned pathways.

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Ritonavir Inhibits NF-AT Activation Through Effects on the PI-3 Kinase/Akt Pathway

Cited by 2 publications

References 0 publications

Protease Inhibitor Treatments Reveal Specific Involvement of Matrix Metalloproteinase-9 in Human Adipocyte Differentiation

Protease Inhibitor Treatments Reveal Specific Involvement of Matrix Metalloproteinase-9 in Human Adipocyte Differentiation

Divulging the Intricacies of Crosstalk Between NF-Kb and Nrf2-Keap1 Pathway in Neurological Complications of COVID-19

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