Connexin43 Hemichannels Contribute to Cadmium-Induced Oxidative Stress and Cell Injury

Fang, Xin; Huang, Tao; Zhu, Ying; Yan, Qiaojing; Chi, Yuan; Jiang, Jean X.; Wang, Peiyu; Matsue, Hiroyuki; Kitamura, Masanori; Yao, Jian

doi:10.1089/ars.2010.3150

Cited by 52 publications

(108 citation statements)

References 53 publications

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“…On the contrary, forced expression of Cx43 in gap-junction-deficient LLC-PK1 cells greatly suppressed AMPK activation, as compared with control cells that had been transfected with a vector encoding a nonfunctional Cx43 mutant (Fig. 2F) (Fang et al, 2011). Similar to the effects in NRK cells, the gap junction blockers heptanol and lindane also potentiated AMPK activation in LLC-PK1 cells expressing wild-type EGFP-Cx43 (data not shown).…”

Section: Blockade Of Cx43 Hemichannels Augments Activation Of Ampkmentioning

confidence: 73%

“…To confirm the above finding, we modified the expression of Cx43 by treating NRK cells with siRNA against Cx43, which is the only connexin molecule expressed in NRK cells (Yao et al, 2010), or by transfection of gap-junction-deficient LLC-PK1 cells with a vector encoding wild-type Cx43 (Fang et al, 2011). As shown in Fig.…”

Section: Blockade Of Cx43 Hemichannels Augments Activation Of Ampkmentioning

confidence: 85%

“…Several studies have pointed to a role for ATP that has been released into the extracellular space. Indeed, hemichannel-derived ATP has been implicated in the transmission of the intercellular Ca 2+ signal and in the control of cell growth, migration and survival (Anselmi et al, 2008;Fang et al, 2011;Pearson et al, 2005;Stout et al, 2002;Zhao et al, 2005). Given that the efflux of ATP through hemichannels leads to an altered intracellular level of ATP, we speculated that hemichannel opening might affect the activation of AMPK and subsequently lead to altered cell behaviors.…”

Section: Introductionmentioning

confidence: 99%

“…The activation of hemichannels has been reported in a variety of pathological situations and has been shown to influence cell responses to various stimuli (Fang et al, 2011;Ramachandran et al, 2007;Thompson et al, 2006). The molecular mechanisms underlying the effects of hemichannels on various cell functions are still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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Purinergic control of AMPK activation by ATP released through connexin 43 hemichannels: pivotal roles in hemichannel-mediated cell injury

Chi

Gao

et al. 2014

Journal of Cell Science

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Connexin hemichannels regulate many cell functions. However, the molecular mechanisms involved remain elusive. Hemichannel opening causes loss of ATP, we therefore speculated a potential role for AMPK in the biological actions of hemichannels. , disclosure of hemichannels similarly enhanced AMPK activity, which protected cells from Cd 2+ -induced cell injury through suppression of mTOR. In summary, our data point to a channel-mediated mechanism for the regulation of AMPK through a purinergic signaling pathway. Furthermore, we define AMPK as a pivotal molecule that underlies the regulatory effects of hemichannels on cell survival.

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Section: Blockade Of Cx43 Hemichannels Augments Activation Of Ampkmentioning

confidence: 73%

Section: Blockade Of Cx43 Hemichannels Augments Activation Of Ampkmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Purinergic control of AMPK activation by ATP released through connexin 43 hemichannels: pivotal roles in hemichannel-mediated cell injury

Chi

Gao

et al. 2014

Journal of Cell Science

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“…Cigarette smoke extract, H2O2 or OS induced by chemical ischemia, oxygen or glucose deprivation are shown to induce hemichannel opening, which leads to cell death (17)(18)(19). Additionally, Cx43 hemichannels cause cadmium- induced cell death of renal epithelial cells (20). This discrepancy between the roles of Cx43 hemichannel function in cell death versus protection could be caused by the activity and duration of the opening of hemichannels.…”

Section: Discussionmentioning

confidence: 99%

Elevated Intracellular Ca2+ Signals by Oxidative Stress Activate Connexin 43 Hemichannels in Osteocytes

Riquelme

Jiang

2013

Bone Res.

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Elevated oxidative stress (OS) during aging leads to bone loss. OS increases intracellular Ca 2+ ([Ca2+ IntroductionIn oxidation-related cellular damage, an increase in the intracellular Ca 2+ ([Ca 2+ ]i) concentration is known to Osteocytes, comprising of approximately 95% of all bone cells, are embedded inside of the bone matrix. Their long dendritic processes form a communication network between neighboring osteocytes and with cells on the bone surface to regulate bone remodeling. During aging, the number of viable osteocytes decreases gradually (1). Oxidative stress (OS) is thought to be a major factor attributing to osteocyte apoptosis and subsequent bone loss (2). 356the exchange of small molecules (up to ~1 kDa) (7). Hemichannels are formed by 6 Cx proteins. Cx43 is the major connexin isoform expressed in bone cells and the activity of hemichannels induced by OS is primarily mediated by Cx43 hemichannels (8). Cx43 hemichannels have been shown to regulate the release of NAD + , prostaglandin E2 (PGE2), and ATP in response to mechanical stimulation in osteocytes (8). Cx43 plays a critical role in many aspects of bone cell function, including proliferation, survival, and differentiation of osteoblasts, skeletal development, and postnatal bone mass acquisition (9-10). Furthermore, Cx43 is shown to be required for the anti-apoptotic effect of bisphosphonates on osteoblasts and osteocytes in vivo (11). However, the cellular mechanism that regulates the activity of Cx43 hemichannels by OS is poorly understood. In this study, we uncovered the role of intracellular Ca 2+ rise induced by OS in the regulation of Cx43 hemichannels. These findings will ultimately help to illustrate the underlying mechanism of Cx43 hemichannel opening and OSinduced Ca 2+ signals in osteocytic cell death and bone aging. Materials and Methods MaterialsFetal bovine serum (FBS) and calf serum (CS) were from HyClone Laboratories (Logan, UT, USA); rat tail collagen type I, 99% pure, was from Becton Dickinson Laboratories (Bedford, MA, USA); Fluo-4 AM were from Invitrogen (Eugene, OR, USA); EZ-link Sulfo-NHS-LC-Biotin and NeutrAvidine from Pierce Biotechnology (Rockford, IL, USA); paraformaldehyde (16% stock solution) was from Electron Microscopy Science (Fort Washington, PA, USA); nitrocellulose membrane was from Schleicher & Schuell (Keene, NH, USA); Enhanced Chemiluminescence (ECL) kit was from Amersham Biosciences (Piscataway, NJ, USA); X-OMAT AR films were from Eastman Kodak (Rochester, NY, USA). All other chemicals were from either Sigma (St. Louis, MO, USA) or Fisher Scientific (Pittsburgh, PA, USA).Cell culture MLO-Y4 cells were cultured on collagen-coated (rat tail collagen type I; 0.15 mg·mL -1 ) surfaces. Cells were grown in α-modified essential medium (MEM) supplemented with 2.5% FBS and 2.5% CS, and incubated in a 5% CO2 incubator at 37 ℃ as described previously (12). [Ca 2+ ]i changes were monitored in MLO-Y4 cells plated on collagen coated glass bottom cell culture plate (MatTek, Ashland, MA, USA). Cells were ester-loaded wi...

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Carbon monoxide: A new player in the redox regulation of connexin hemichannels

et al. 2015

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Carbon monoxide (CO) is a gaseous transmitter that is known to be involved in several physiological processes, but surprisingly it is also becoming a promising molecule to treat several pathologies including stroke and cancer. CO can cross the plasma membrane and activate guanylate cyclase, increasing the cGMP concentration and activating some kinases, including PKG. The other mechanism of action involves induction of protein carbonylation. CO is known to directly and indirectly modulate the function of ion channels at the plasma membrane, which in turn have important repercussions in the cellular behavior. One group of these channels is hemichannels, which are formed by proteins known as connexins (Cxs). Hemichannel allows not only the flow of ions through their pore but also the release of molecules such as ATP and glutamate. Therefore, their modulation not only impacts cellular function but also cellular communication, having the capability to affect tissular behavior. Here, we review the most recent results regarding the effect of CO on Cx hemichannels and their possible repercussions on pathologies. V C 2015 IUBMB Life, 67(6): [428][429][430][431][432][433][434][435][436][437] 2015

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Connexin43 Hemichannels Contribute to Cadmium-Induced Oxidative Stress and Cell Injury

Cited by 52 publications

References 53 publications

Purinergic control of AMPK activation by ATP released through connexin 43 hemichannels: pivotal roles in hemichannel-mediated cell injury

Purinergic control of AMPK activation by ATP released through connexin 43 hemichannels: pivotal roles in hemichannel-mediated cell injury

Elevated Intracellular Ca2+ Signals by Oxidative Stress Activate Connexin 43 Hemichannels in Osteocytes

Carbon monoxide: A new player in the redox regulation of connexin hemichannels

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