Inhaled marijuana smoke disrupts mitochondrial energetics in pulmonary epithelial cells in vivo

Sarafian, Theodore A.; Habib, Nancy; Oldham, Michael J.; Seeram, Navindra P.; Lee, Ru-Po; Lin, Laura; Tashkin, Donald P.; Roth, Michael D.

doi:10.1152/ajplung.00371.2005

Cited by 63 publications

(54 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The pattern of selective response to marijuana smoke extract relative to tobacco or placebo extracts was similar to the pattern observed previously for loss of Ψ m in A549 cells and in an in vivo smoke inhalation model (Sarafian et al, 2003;Sarafian et al, 2006). This similarity raised the possibility of a causal relationship between THC-mediated disruption of mitochondrial energetics and its effects on chemotaxis.…”

Section: Role Of Mitochondrial Injury In Thc-induced Chemotaxis Inhibsupporting

confidence: 82%

“…In both primary human lung epithelial cells and the lung tumor cell line, A549, mitochondrial membrane potential (Ψ m ) is diminished along with cellular ATP level. We have also performed in vivo smoke inhalation studies with rats exposed to marijuana smoke and found reduced mitochondrial-pattern staining using the potentiometric probe, JC-1, suggesting that marijuana smoke may impair epithelial cell energetics in humans (Sarafian et al, 2006). These events do not occur upon exposure to tobacco smoke suggesting that marijuana smokers may be at risk of physiological impairment distinct from that of tobacco smokers.…”

Section: Introductionmentioning

confidence: 87%

“…In a small animal smoke inhalation model we recently demonstrated that cannabinoid levels are 5-to 10-fold higher in lung tissue as compared to the levels measured in blood (Sarafian et al, 2006). Habitual marijuana smokers frequently complain of chronic cough and sputum production and their airways appear grossly-inflamed and edematous Aldington et al, 2007).…”

Section: Introductionmentioning

confidence: 95%

See 2 more Smart Citations

Clarifying CB2 receptor-dependent and independent effects of THC on human lung epithelial cells

Sarafian

Montes

Harui

et al. 2008

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

Marijuana smoking is associated with a number of abnormal findings in the lungs of habitual smokers. Previous studies revealed that Δ 9 -tetrahydrocannabinol (THC) caused mitochondrial injury in primary lung epithelial cells and in the cell line, A549 (Sarafian et al., 2003;Sarafian et al., 2005). The role of cannabinoid receptors in this injury was unclear, as was the potential impact on cell function. In order to investigate these questions, A549 cells were engineered to over-express the type 2 cannabinoid receptor (CB2R) using a self-inactivating lentiviral vector. This transduction resulted in a 60-fold increase in CB2R mRNA relative to cells transduced with a control vector. Transduced cell lines were used to study the effects of THC on chemotactic activity and mitochondrial function. Chemotaxis in response to a 10 % serum gradient was suppressed in a concentration-dependent manner by exposure to THC. CB2R-transduced cells exhibited less intrinsic chemotactic activity (p < 0.05) and were 80-to 100-fold more sensitive to the inhibitory effects of THC. Studies using SR144528, a selective CB2R antagonist, verified that these effects were mediated by the CB2R. Marijuana smoke extract, but not smoke extracts from tobacco or placebo marijuana cigarettes, reproduced these effects (p < 0.05). THC decreased ATP level and mitochondrial membrane potential (Ψ m ) in both control and CB2R-transduced cells. However, these decreases did not play a significant role in chemotaxis inhibition since cyclosporine A, which protected against ATP loss, did not increase cell migration. Moreover, CB2R-transduced cells displayed higher Ψ m than did control cells. Since both Ψ m and chemotaxis are regulated by intracellular signaling, we investigated the effects of THC on the activation of multiple signaling pathways. Serum exposure activated several signaling events of which phosphorylation of IκB-α and JNK were regulated in a CB2R-and THC-dependent manner. We conclude that airway epithelial cells are sensitive to both CB2R-dependent and independent effects mediated by THC.

show abstract

Section: Role Of Mitochondrial Injury In Thc-induced Chemotaxis Inhibsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 95%

See 1 more Smart Citation

Clarifying CB2 receptor-dependent and independent effects of THC on human lung epithelial cells

Sarafian

Montes

Harui

et al. 2008

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

show abstract

“…46 Thus, when taken together with apoC-III-mediated decreases in the rate of mitochondrial respiration, 47 the observed increases in apoC-III in the MJ users hint to the possibility that chronic MJ abuse could lead to impairments of cellular energetics and mitochondrial function, which are critical events associated to myocardial infarction, stroke and ischemic/reperfusion damage. 48 This discussion might offer a partial explanation for the chronic effects of the drug on cardiac and cerebrovascular systems. [49][50][51] The manner by which chronic MJ smoking might cause these increases in serum apoC-III levels remains to be clarified.…”

Section: Discussionmentioning

confidence: 99%

Heavy marijuana users show increased serum apolipoprotein C-III levels: evidence from proteomic analyses

Jayanthi¹,

S²,

Moore³

et al. 2008

Mol Psychiatry

View full text Add to dashboard Cite

Marijuana (MJ) is the most commonly used illicit drug in the United States. Its abuse is associated with cognitive dysfunctions and increased resistance to blood flow in the cerebral vasculature. In addition, MJ abuse is associated with increased risks of potentially serious cardiovascular disorders. In the present study, we used the protein chip platform based on surface-enhanced laser desorption/ionization time-of-flight mass spectroscopy (SELDI-TOF-MS) to test the possibility that MJ abuse might be associated with changes in serum protein levels. Indeed, MJ users showed significant increases in three protein peaks, which were identified as three isoforms of apolipoprotein (apo) C-III. Immunoprecipitation using an apoC-III antibody also validated the identification of the proteins. Marijuana-induced increases in apoC-III levels might occur through chronic stimulation of hepatic cannabinoid receptors (CB1 and/or CB2) by its active ingredient, D 9 tetrahydrocannibol (THC). Thus, chronic MJ abuse might cause increased transcription and/or translation of apoC-III in the liver with corresponding changes reflected in the plasma of these patients. In any case, because apoC-III is a cardiovascular risk factor, the increased levels observed in MJ users might explain, in part, the cardiac and cerebral abnormalities reported in these patients.

show abstract

“…Free radical generation both at receptor binding (S.T. Carney, North Carolina Central University, Durham, NC, USA; personal communication) and by mitochondrial uncoupling [4] has been demonstrated.…”

Section: Referencesmentioning

confidence: 99%

Cannabis and lung cancer

Reece¹

2008

European Respiratory Journal

View full text Add to dashboard Cite

Inhaled marijuana smoke disrupts mitochondrial energetics in pulmonary epithelial cells in vivo

Cited by 63 publications

References 31 publications

Clarifying CB2 receptor-dependent and independent effects of THC on human lung epithelial cells

Clarifying CB2 receptor-dependent and independent effects of THC on human lung epithelial cells

Heavy marijuana users show increased serum apolipoprotein C-III levels: evidence from proteomic analyses

Cannabis and lung cancer

Contact Info

Product

Resources

About