<i>Helicobacter pylori</i> lipopolysaccharide activates Rac1 and transcription of NADPH oxidase Nox1 and its organizer NOXO1 in guinea pig gastric mucosal cells

Kawahara, Tsukasa; Kohjima, Motoyuki; Kuwano, Yuki; Mino, Hisano; Teshima-Kondo, Shigetada; Takeya, Ryu; Tsunawaki, Shohko; Wada, Akihiro; Sumimoto, Hideki; Rokutan, Kazuhito

doi:10.1152/ajpcell.00319.2004

Cited by 130 publications

(99 citation statements)

References 42 publications

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“…Several biochemical studies indicate that like gp91 phox , Nox1 activity is also governed by regulatory subunits, in this case NOXO1 and NOXA1, since Nox1-dependent reactive oxygen generation required co-expression of both NOXO1 and NOXA1 (30 -33). In addition, NOXO1 and Nox1 are coordinately expressed in the gastrointestinal tract, consistent with NOXO1 as a physiological regulatory subunit for Nox1 (31,34,35).…”

Section: Whereas P22mentioning

confidence: 53%

Point Mutations in the Proline-rich Region of p22 Are Dominant Inhibitors of Nox1- and Nox2-dependent Reactive Oxygen Generation

Kawahara

Ritsick

Cheng

et al. 2005

Journal of Biological Chemistry

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207

204

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The integral membrane protein p22phox is an indispensable component of the superoxide-generating phagocyte NADPH oxidase, whose catalytic core is the membrane-associated gp91 phox (also known as Nox2). p22 phox associates with gp91 phox and, through its proline-rich C terminus, provides a binding site for the tandem Src homology 3 domains of the activating subunit p47 phox . Whereas p22phox is expressed ubiquitously, its participation in regulating the activity of other Nox enzymes is less clear. This study investigates the requirement of p22 phox for Nox enzyme activity and explores the role of its proline-rich region (PRR) for regulating activity. Coexpression of specific Nox catalytic subunits (Nox1, Nox2, Nox3, Nox4, or Nox5) along with their corresponding regulatory subunits (NOXO1/NOXA1 for Nox1; p47 phox / p67 phox /Rac for Nox2; NOXO1 for Nox3; no subunits for Nox4 or Nox5) resulted in marked production of reactive oxygen. Small interfering RNAs decreased endogenous p22 phox expression and inhibited reactive oxygen generation from Nox1, Nox2, Nox3, and Nox4 but not Nox5. Truncated forms of p22 phox that disrupted the PRR-inhibited reactive oxygen generation from Nox1, Nox2, and Nox3 but not from Nox4 and Nox5. Similarly, p22 phox (P156Q), a mutation that disrupts Src homology 3 binding by the PRR, potently inhibited reactive oxygen production from Nox1 and Nox2 but not from Nox4 and Nox5. Expression of p22 phox (P156Q) inhibited NOXO1-stimulated Nox3 activity, but co-expression of NOXA1 overcame the inhibitory effect. The P157Q and P160Q mutations of p22 phox showed selective inhibition of Nox2/p47 phox /p67 phox , and selectivity was specific for the organizing subunit (p47 phox or NOXO1) rather than the Nox catalytic subunit. These studies stress the importance of p22 phox for the function of Nox1, Nox2, Nox3, and Nox4, and emphasize the key role of the PRR for regulating Nox proteins whose activity is dependent upon p47 phox or NOXO1.

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Section: Whereas P22mentioning

confidence: 53%

Point Mutations in the Proline-rich Region of p22 Are Dominant Inhibitors of Nox1- and Nox2-dependent Reactive Oxygen Generation

Kawahara

Ritsick

Cheng

et al. 2005

Journal of Biological Chemistry

Self Cite

207

204

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“…Noxa1 was designated as a "Nox activator" based on its homology to p67 phox , which binds to Rac1 or Rac2 and plays a more direct role in modulating oxidase activity. Recent evidence suggests that Rac1 also regulates Nox1 most likely through GTP-dependent interactions with the Nox activator, Noxa1 [16][17][18][19] We showed that the association of Noxa1 with the plasma membrane depends on its interaction with Noxo1 [17]. These structural and functional similarities between the Nox and phox regulators may explain why Noxo1 and Noxa1 can function in partially compensating for p47 phox and p67 phox in supporting Nox2 activity [8,[13][14][15].…”

Section: Introductionmentioning

confidence: 60%

Subcellular localization and function of alternatively spliced Noxo1 isoforms

Ueyama

Lekstrom

Tsujibe

et al. 2007

Free Radical Biology and Medicine

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Nox organizer 1 (Noxo1), a p47 phox homolog, is produced as four isoforms with unique N-terminal PX domains derived by alternative mRNA splicing. We compared the subcellular distribution of these isoforms or their isolated PX domains produced as GFP fusion proteins, as well as their ability to support Nox1 activity in several transfected models. Noxo1α, β, γ, and δ show different subcellular localization patterns, determined by their PX domains. In HEK293 cells, Noxo1β exhibits prominent plasma membrane binding, Noxo1γ shows plasma membrane and nuclear associations, Noxo1α and δ localize primarily on intracellular vesicles or cytoplasmic aggregates, but not the plasma membrane. Nox1 activity correlates with Noxo1 plasma membrane binding in HEK293 cells, since Noxo1β supports the highest activity and Noxo1γ and Noxo1α support moderate or low activities, respectively. In COS-7 cells, where Noxo1α localizes on the plasma membrane, the activities supported by the three isoforms (α, β, and γ) do not differ significantly. The PX domains of β and γ bind the same phospholipids, including phosphatidic acid. These results indicate the variant PX domains are unique determinants of Noxo1 localization and Nox1 function. Finally, the overexpressed Noxo1 isoforms do not affect p22 phox localization, although Nox1 is needed to transport p22 phox to the plasma membrane.

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“…platelet-derived growth factor induce the expression of Nox1 in vascular smooth muscle cells [28][29][30][31][32][33]. Moreover, it has been demonstrated that mitochondrial-derived ROS positively regulate the expression of Nox1 [34], and that LPS-stimulated expression of Nox1 was profoundly suppressed in the presence of antioxidants [35]. Thus, the expression of Nox1 appears to be regulated by complex systems which differ according to the kind of cells.…”

Section: Discussionmentioning

confidence: 99%

Ionizing irradiation induces apoptotic damage of salivary gland acinar cells via NADPH oxidase 1-dependent superoxide generation

Tateishi

Sasabe

Ueta

et al. 2008

Biochemical and Biophysical Research Communications

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Helicobacter pylori lipopolysaccharide activates Rac1 and transcription of NADPH oxidase Nox1 and its organizer NOXO1 in guinea pig gastric mucosal cells

Abstract: pylori lipopolysaccharide activates Rac1 and transcription of NADPH oxidase Nox1 and its organizer NOXO1 in guinea pig gastric mucosal cells.

Cited by 130 publications

References 42 publications

Point Mutations in the Proline-rich Region of p22 Are Dominant Inhibitors of Nox1- and Nox2-dependent Reactive Oxygen Generation

Point Mutations in the Proline-rich Region of p22 Are Dominant Inhibitors of Nox1- and Nox2-dependent Reactive Oxygen Generation

Subcellular localization and function of alternatively spliced Noxo1 isoforms

Ionizing irradiation induces apoptotic damage of salivary gland acinar cells via NADPH oxidase 1-dependent superoxide generation

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