p38 MAPK mediates renal tubular cell TNF-α production and TNF-α-dependent apoptosis during simulated ischemia

Meldrum, Kirstan K.; Meldrum, Daniel R.; Hile, Karen L.; Yerkes, Elizabeth B.; Ayala, Alfred; Cain, Mark P.; Rink, Richard C.; Casale, Anthony J.; Kaefer, Martin

doi:10.1152/ajpcell.2001.281.2.c563

Cited by 101 publications

(75 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was reported that elevated plasma levels of inflammatory cytokines were related to heart dysfunction (Chen et al 2003;Meldrum et al 2001;Peng et al 2003). Previous studies have accumulated much evidence that the changes of inflammatory cytokines, such as some TNF-a and IL-6, plays an important role in the process of pathological heart remodeling.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, p38 MAPK-mediated inhibition of TNF-a expression was reported during simulated ischemia (Meldrum et al 2001). Furthermore, it was reported in renal tubular cell activation of p38 MAPK enhances TNF-a secretion and induced apoptosis (Meldrum et al 2001). These observations led us to hypothesize that TNF-a and p38 MAPK are mutual activated through oxidative stress-induced pathways in cardiac cells.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

H2O2-induced secretion of tumor necrosis factor-α evokes apoptosis of cardiac myocytes through reactive oxygen species-dependent activation of p38 MAPK

et al. 2011

View full text Add to dashboard Cite

P38 mitogen-activated protein kinases (p38 MAPK) and tumor necrosis factor-a (TNF-a) play important roles in oxidative stress-induced apoptosis in cardiac myocytes. However, the regulation and functional role of cross-talk between p38 MAPK and TNF-a pathways have not yet been fully characterized in cardiac myocytes. In this study, we found that inhibition of p38 MAPK with SB-203580 (SB) reduced H 2 O 2 -stimulated secretion of TNF-a, whereas pre-activation of p38 MAPK with sodium arsenite (SA) enhanced H 2 O 2 -stimulated secretion of TNF-a. In addition, pretreatment of cells with TNF-a increased basal and H 2 O 2 -stimulated p38 MAPK and apoptosis of cardiac myocytes, and p38 MAPK-associated apoptosis of cardiac myocytes induced by TNF-a was blocked by inhibition of p38 MAPK with SB. Finally, H 2 O 2 -induced apoptosis was attenuated by the inhibitors of p38 MAPK or reactive oxygen species (ROS), whereas it was enhanced by p38 MAPK agonist SA. These results suggest that H 2 O 2 -induced secretion of TNF-a increases apoptosis of cardiac myocytes through ROS-dependent activation of p38 MAPK. This may represent a novel mechanism that TNF-a partly interplays with p38 MAPK pathways during oxidative stress-modulated apoptosis in cardiac myocytes.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

H2O2-induced secretion of tumor necrosis factor-α evokes apoptosis of cardiac myocytes through reactive oxygen species-dependent activation of p38 MAPK

et al. 2011

View full text Add to dashboard Cite

show abstract

“…In the current study, dilated tubules in diabetic kidneys appeared to have an increased proportion of p-p38+ cells, suggesting that increased phosphorylation of tubular p38 also occurs in response to tubular injury. Phosphorylation of p38 in tubular cells can, in turn, promote production of TNF-α and epithelial transdifferentiation into myofibroblasts [40,41], which can subsequently increase interstitial inflammation and fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Abnormal p38 mitogen-activated protein kinase signalling in human and experimental diabetic nephropathy

et al. 2004

View full text Add to dashboard Cite

Aims/hypothesis. Inflammation and fibrosis are pathological mechanisms that are partially regulated by cell signalling through the p38 mitogen-activated protein kinase (MAPK) pathway. Elements of the diabetic milieu such as high glucose and advanced glycation endproducts induce activation of this pathway in renal cells. Therefore, we examined whether p38 MAPK signalling is associated with the development of human and experimental diabetic nephropathy. Methods. Immunostaining identified phosphorylated (active) p38 MAPK in human biopsies with no abnormality (n=6) and with Type 2 diabetic nephropathy (n=12). Changes in kidney levels of phosphorylated p38 were assessed by immunostaining and western blotting in mice with streptozotocin-induced Type 1 diabetes that had been killed after 0.5, 2, 3, 4 and 8 months, and in Type 2 diabetic db/db mice at 2, 4, 6 and 8 months of age. Results. Phosphorylated p38 was detected in some intrinsic cells in normal human kidney, including podocytes, cortical tubules and occasional interstitial cells. Greater numbers of these phosphorylated p38+ cells were observed in diabetic patients, and phosphorylated p38 was identified in accumulating interstitial macrophages and myofibroblasts. A similar pattern of p38 activation was observed in both mouse models of diabetes. In mice, kidney levels of phosphorylated p38 increased (2-6 fold) following the onset of Type 1 and Type 2 diabetes. In both mouse models, interstitial phosphorylated p38+ cells were associated with hyperglycaemia, increased HbA 1 c levels and albuminuria. Further assessment of streptozotocin-induced diabetic nephropathy showed that interstitial phosphorylated p38+ cells correlated with interstitial fibrosis (myofibroblasts, collagen). Conclusions/interpretation. Increased p38 MAPK signalling is a feature of human and experimental diabetic nephropathy. Time course studies in mouse models suggest that phosphorylation of p38 plays a pathological role, particularly in the development of interstitial fibrosis.

show abstract

“…TNF-␣ is produced by the kidney after renal ischemia in vivo (see review, reference 9) and by hypoxic LL-CPK 1 renal tubule cells in vitro (10). Injury is ameliorated by TNF-␣ receptor antagonists (11) or anti-TNF-␣ monoclonal antibodies (12).…”

mentioning

confidence: 99%

Docosahexaenoic Acid Ameliorates Murine Ischemic Acute Renal Failure and Prevents Increases in mRNA Abundance for both TNF-α and Inducible Nitric Oxide Synthase

Kielar¹,

Jeyarajah²,

Zhou³

et al. 2003

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Abstract. This study demonstrates that intraperitoneal injections of DHA (all cis 4,7,10,13,16,19 docosahexaenoic acid C22: n-3) bound to bovine serum albumin ameliorate murine acute renal failure (ARF) induced by temporary occlusion of the renal artery. Three micromoles of DHA decreased serum creatinine (Scr) from 2.3 mg/dl to 1.1 mg/dl 24 h after reperfusion (n ϭ 15; P Ͻ 0.05). Scr of the treated animals were significantly lower than controls throughout a 7-d time course. Although lower doses of DHA were less effective, higher doses were not more effective. Ribonuclease (RNase) protection assays showed that ischemia increased mRNA abundance for TNF-␣ and inducible nitric oxide synthase (iNOS) at 24 h. This increase was prevented by DHA administration. Because TNF-␣ and iNOS contribute to renal ischemic injury, their inhibition may contribute to DHA's salutary effect. In addition, the data may have therapeutic implications, because the DHA improves ARF even when administered at 4 h after reperfusion.

show abstract

p38 MAPK mediates renal tubular cell TNF-α production and TNF-α-dependent apoptosis during simulated ischemia

Cited by 101 publications

References 56 publications

H2O2-induced secretion of tumor necrosis factor-α evokes apoptosis of cardiac myocytes through reactive oxygen species-dependent activation of p38 MAPK

H2O2-induced secretion of tumor necrosis factor-α evokes apoptosis of cardiac myocytes through reactive oxygen species-dependent activation of p38 MAPK

Abnormal p38 mitogen-activated protein kinase signalling in human and experimental diabetic nephropathy

Docosahexaenoic Acid Ameliorates Murine Ischemic Acute Renal Failure and Prevents Increases in mRNA Abundance for both TNF-α and Inducible Nitric Oxide Synthase

Contact Info

Product

Resources

About