Involvement of Apoptosis Signal-Regulating Kinase-1 on Angiotensin II-Induced Monocyte Chemoattractant Protein-1 Expression

Abstract

Objective-Monocyte chemoattractant protein 1 (MCP-1) could contribute to enhanced leukocyte recruitment and activation resulting in chronic tissue damage. However, little is known about the molecular mechanisms of cardiac MCP-1 expression. To elucidate these molecular mechanisms, angiotensin II-induced expression of MCP-1 was examined in cultured rat neonatal ventricular cardiomyocytes and fibroblasts by adenovirus gene transfer. Methods and Results-MCP-1 mRNA increased 3.6-fold in cardiac fibroblasts at 3 hours after 100 nmol/L angiotensin-II stimulation (PϽ0.01), whereas MCP-1 mRNA in cardiomyocytes was unchanged. Angiotensin II significantly enhanced JNK, p38MAPK, and nuclear factor-B (NF-B) activities of cardiac fibroblasts. Wild-type ASK-1 increased MCP-1 expression of cardiac fibroblasts, whereas dominant negative mutant of ASK-1 (DN-ASK), dominant negative mutant of p38MAPK (DN-p38MAPK), and pyrrolidine dithiocarbamate significantly inhibited such expression. The increased MCP-1 mRNA expression in wild-type ASK-1 transfected fibroblasts was inhibited by cotransfection with adenovirus expressing DN-p38MAPK. On the contrary, the decreased MCP-1 mRNA expression in DN-ASK transfected cells was increased by cotransfection with adenovirus expressing constitutively active MKK6. Key Words: apoptosis signal-regulating kinase-1 Ⅲ monocyte chemoattractant protein-1 Ⅲ cardiac fibroblast Ⅲ angiotensin II Ⅲ p38 MAPK Conclusion-Angiotensin

Tissue kallikrein infusion prevents cardiomyocyte apoptosis, inflammation and ventricular remodeling after myocardial infarction

“…NF-κB is a ubiquitous rapid response transcription factor that modulates the expression of various cytokine and adhesion molecules. Activation of NF-κB up-regulates the expression of proinflammatory genes, such as vascular cell adhesion molecule 1 (VCAM-1) and monocyte chemoattractant protein 1 (MCP-1), that play pivotal roles in inflammation after ischemia [7,8]. These findings suggest that intervention with exogenous anti-oxidants may attenuate myocardial damage by inhibiting cardiomyocyte apoptosis and blunting the inflammatory response.…”

Angiotensin II enhances the increase in monocyte chemoattractant protein-1 production induced by tumor necrosis factor-α from 3T3-L1 preadipocytes

“…It has been reported that Ang II stimulates MCP-1 production from various cells including mononuclear cells, cardiovascular cells, preadipocytes, and adipocytes (Funakoshi et al 2001, Omura et al 2004, Tsuchiya et al 2006. In our Figure 4 Translocation of NF-kB p65 from cytosol to nucleus induced by Ang II and/or TNF-a.…”

“…Such inflammatory cytokines as TNF-a and angiotensin II (Ang II) are molecules reported to induce MCP-1 gene expression (Funakoshi et al 2001, Fain et al 2004, Omura et al 2004. The renin-angiotensin system (RAS) has been shown to be another important pathway in the pathogenesis of metabolic syndrome, especially in hypertension.…”

“…These findings suggest that the adipose RAS may play important roles in the pathogenesis of obesity, obesity-associated hypertension, and insulin resistance. Several reports have described that MCP-1 production induced by Ang II is mediated by extracellular signalingregulated kinase 1/2 (ERK1/2), p38MAPK or NF-kB pathway in cardiovascular cells such as smooth muscle cells (Funakoshi et al 2001) and cardiac fibroblasts (Omura et al 2004). However, the cellular signaling mechanism of Ang II-induced MCP-1 production has not been fully examined.…”

Growth inhibition of colon cancer cells by transfection of dominant-negative apoptosis signal-regulating kinase-1

“…Moreover, antioxidants such as thioredoxin, a physiological inhibitor of ASK-1, inhibit cytokine-and stress-induced apoptosis (3)(4)(5)(6). Cardiac myocyte hypertrophy, a characteristic of cardiac remodeling, requires activation of ASK-1 and nuclear factor κB (16). Thus, ASK-1 is considered essential for a variety of physiological functions, such as apoptosis (7).…”