Biomedical subjects

Tsuneo Konta

Publications and source records attributed to Tsuneo Konta.

5 recordsLinked to original sources

PubMed2003

Fibrillary glomerulonephritis with hypocomplementemia.

A 59-year-old man was referred for evaluation of nephrotic syndrome. The patient was diagnosed to have rheumatoid arthritis and had been treated for 10 years. Renal biopsy showed mesangial proliferation with small nodular formations, which were determined as fibrillary deposits (average diameter: 20 nm) by electromicroscopy. Congo-red stain was negative. The laboratory findings revealed hypocomplementemia and lambda type of Bence-Jones protein in urine without other systemic diseases including multiple myeloma. Immunosuppressive therapy did not attenuate the nephrotic-range proteinuria. Such a case of fibrillary glomerulonephritis with hypocomplementemia is rare.

Anti-Inflammatory Agents↗

PubMed2002

Transcriptional induction of mitogen-activated protein kinase phosphatase 1 by retinoids. Selective roles of nuclear receptors and contribution to the antiapoptotic effect.

All-trans-retinoic acid (t-RA) inhibits hydrogen peroxide (H(2)O(2))-induced apoptosis by inhibiting the c-Jun N-terminal kinase (JNK)-activator protein 1 (AP-1) pathway. In this report, we examined the involvement of mitogen-activated protein kinase phosphatase 1 (MKP-1) in suppression of JNK and the antiapoptotic effect of t-RA and the roles of nuclear receptors in the regulation of MKP-1 by t-RA. We found that not only t-RA, but also a selective agonist of retinoic acid receptor (RAR), a selective agonist of retinoid X receptor (RXR), and a pan-agonist of RAR and RXR all induced MKP-1 at the transcriptional level. Activation of RAR was required for all of these triggering effects, but activation of RXR was required only for the RXR agonist-induced MKP-1 expression. Among the three RAR subtypes, RARalpha and RARgamma, but not RARbeta, mediated the t-RA-induced MKP-1 expression. The antiapoptotic effect of t-RA on H(2)O(2)-induced apoptosis in several cell types was correlated with the inducibility of MKP-1 by t-RA. Inhibition of MKP-1 by vanadate enhanced JNK phosphorylation and attenuated the antiapoptotic effect of t-RA. Furthermore, overexpression of MKP-1 inhibited H(2)O(2)-induced JNK phosphorylation and apoptosis. To our knowledge, this is the first to demonstrate that 1) MKP-1 is inducible by retinoids at the transcriptional level, 2) RXR and individual RAR subtypes have different roles in this process, and 3) the induced MKP-1 plays a significant role in mediating both JNK inhibition and the antiapoptotic effect of t-RA in oxidative stress.

Animals↗

PubMed2002

Intervention by retinoic acid in oxidative stress-induced apoptosis.

Retinoic acid (RA) has been considered a pro-apoptotic agent, and little is known about its anti-apoptotic potential. In this article, we describe that RA strongly inhibits hydrogen peroxide (H(2)O(2))-induced apoptosis of mesangial cells by intervention in activator protein 1 (AP-1). Our data showed that: (i) H(2)O(2) induces apoptosis of mesangial cells via the AP-1 pathway; (iii) activation of AP-1 by H(2)O(2) is mediated by the c-Jun N-terminal kinase (JNK)-c-Jun/AP-1 pathway and the extracellular signal-regulated kinase-c-Fos/AP-1 pathway; (iii) RA inhibits H(2)O(2)-induced apoptosis via suppression of c-fos/c-jun expression and JNK activation; and (iv) the anti-apoptotic effect of RA is, at least in part, mediated by induction of mitogen-activated protein kinase phosphatase 1.

Animals↗

PubMed2002

Retinoic acid regulation of mesangial cell apoptosis.

Retinoic acid (RA) is recently used for the treatment of experimental glomerular diseases. However, mechanisms underlying its therapeutic effects are largely unknown. We recently reported that RA has the potential for protecting certain cells from particular injury. A typical example is its effect on oxidant-induced apoptosis of mesangial cells. Mesangial cells exposed to hydrogen peroxide undergo apoptosis through activation of the c-Jun N-terminal kinase activator protein 1 pathway. RA dramatically inhibits this process via suppression of c-fos/c-jun expression and inhibition of the c-Jun N-terminal kinase activation. The anti-apoptotic effect of RA is mediated by both nuclear receptor dependent and nuclear receptor independent mechanisms and is, at least in part, mediated by induction of mitogen-activated protein kinase phosphatase 1. In this review, we briefly summarize the current knowledge on molecular mechanisms involved in the anti-apoptotic effects of RA.

Apoptosis↗

PubMed2001

Suppression of constitutive but not Il-1beta-inducible expression of monocyte chemoattractant protein-1 in mesangial cells by retinoic acids: intervention in the activator protein-1 pathway.

Retinoic acid regulates a wide range of biologic processes, including inflammation. This study investigated the effect of all-trans-retinoic acid (t-RA) on the constitutive and cytokine-inducible expression of monocyte chemoattractant protein 1 (MCP-1) in rat mesangial cells. Serum-deprived mesangial cells exhibited substantial levels of MCP-1 mRNA, and the expression was markedly upregulated by interleukin-1beta (IL-1beta). Pretreatment with t-RA abrogated the constitutive mRNA expression but did not inhibit the IL-1beta-inducible expression. The similar effects were observed by 9-cis-RA. The suppressive effect of t-RA required retinoic acid receptors. t-RA did not affect the stability of MCP-1 mRNA, indicating that its suppressive effect was at the transcriptional level. Experiments that used pharmacologic and genetic inhibitors showed that the IL-1beta-inducible MCP-1 expression was dependent on nuclear factor-kappaB (NF-kappaB) and independent of activator protein 1 (AP-1). In contrast, the constitutive expression of MCP-1 was dependent on both NF-kappaB and AP-1. t-RA substantially inhibited the constitutive activity of AP-1 but did not inhibit NF-kappaB activity in mesangial cells. These data suggested that (1) constitutive and IL-1beta-inducible expression of MCP-1 was differently regulated by AP-1 and NF-kappaB and (2) t-RA inhibited selectively the constitutive expression of MCP-1 via intervention in the AP-1 pathway.

Alitretinoin↗