Cannabinoid receptor 1 mediates high glucose-induced apoptosis via endoplasmic reticulum stress in primary cultured rat mesangial cells

Lim, Jae Cheong; Lim, Seul Ki; Park, Min Jung; Kim, Gye Yeop; Han, Ho Jae; Park, Soo Hyun

doi:10.1152/ajprenal.00032.2010

Cited by 44 publications

(38 citation statements)

References 64 publications

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“…A similar observation for increased CB 1 receptor expression and its cellular internalization was recently reported in primary rat mesangial cells exposed to HG conditions [50]. The effect of HG on these cells induces apoptosis via NF-κB and phospholipase A 2 stimulation, which, in turn, reduces expression of the ER stress chaperone GRP78 and increases levels of p-PERK, p-eIF2α, pAFT4, and CHOP [50].…”

Section: Role Of Cb 1 Receptors In Dnsupporting

confidence: 72%

“…Several recent reports (Table 1) have documented the presence of functional CB 1 receptor in the entire kidney [15,[33][34][35][36][37][38][40][41][42], including different parts of the nephron such as afferent and efferent arterioles [39], glomeruli [33,38,40,42,43], tubules [15], the loop of Henle [44], and collecting ducts [15]. It is also expressed in various subtypes of kidney cells such as podocytes [33,41,43,45,46], proximal and distal tubular epithelial cells [15,34,37,38,40,41,[47][48][49], and mesangial cells [50,54]. Moreover, CB 1 receptors are expressed in human clear-and chromophobe-renal cell carcinomas, as well as in renal oncocytoma [55,56].…”

Section: The Renal Ecb Systemmentioning

confidence: 99%

“…The effect of HG on these cells induces apoptosis via NF-κB and phospholipase A 2 stimulation, which, in turn, reduces expression of the ER stress chaperone GRP78 and increases levels of p-PERK, p-eIF2α, pAFT4, and CHOP [50]. These ER stress proteins have been also linked to DN development in vivo [72].…”

Section: Role Of Cb 1 Receptors In Dnmentioning

confidence: 99%

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The emerging role of the endocannabinoid system in the pathogenesis and treatment of kidney diseases

Tam

2015

Journal of Basic and Clinical Physiology and Pharmacology

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Endocannabinoids (eCBs) are endogenous lipid ligands that bind to cannabinoid receptors that also mediate the effects of marijuana. The eCB system is comprised of eCBs, anandamide, and 2-arachidonoyl glycerol, their cannabinoid-1 and cannabinoid-2 receptors (CB 1 and CB 2 , respectively), and the enzymes involved in their biosynthesis and degradation. It is present in both the central nervous system and peripheral organs including the kidney. The current review focuses on the role of the eCB system in normal kidney function and various diseases, such as diabetes and obesity, that directly contributes to the development of renal pathologies. Normally, activation of the CB 1 receptor regulates renal vascular hemodynamics and stimulates the transport of ions and proteins in different nephron compartments. In various mouse and rat models of obesity and type 1 and 2 diabetes mellitus, eCBs generated in various renal cells activate CB 1 receptors and contribute to the development of oxidative stress, inflammation, and renal fibrosis. These effects can be chronically ameliorated by CB 1 receptor blockers. In contrast, activation of the renal CB 2 receptors reduces the deleterious effects of these chronic diseases. Because the therapeutic potential of globally acting CB 1 receptor antagonists in these conditions is limited due to their neuropsychiatric adverse effects, the recent development of peripherally restricted CB 1 receptor antagonists may represent a novel pharmacological approach in treating renal diseases.Keywords: CB 1 receptor; CB 2 receptor; diabetic nephropathy; endocannabinoids; obesity; renal function. The endocannabinoid systemThe recreational, psychoactive, and medicinal effects of marijuana, many of which have important therapeutic potentials, have been recognized for thousands of years [1]. Yet, it is only in the last several decades that our understanding of these effects had grown following some landmark discoveries in the field of cannabinoid research. To date, more than 60 plant-derived cannabinoid molecules have been identified in marijuana [2], among which only Δ 9 -tetrahydrocannabinol (THC) is responsible for its psychoactive properties [3]. This initial discovery has allowed the synthesis of structurally modified molecules that have been used to study structure-activity relationships and reveal tight structural and steric selectivity in the biological actions of cannabinoids. Indeed, it took more than two decades to identify the THC binding site in the brain [4], which was later cloned and named cannabinoid-1 (CB 1 ) receptor [5]. In addition to the brain-type CB 1 receptor, a second cannabinoid receptor was identified in lymphoid tissue and was named CB 2 [6]. Both CB 1 and CB 2 receptors, which share a low level (44%) of sequence homology [6], are G protein-coupled receptors that mainly signal via G i /G o proteins, even though they may also activate G s , G q/11 , and G protein-independent signaling pathways [7]. These receptors are expressed in the brain [8][9][10], liver [11,...

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Section: Role Of Cb 1 Receptors In Dnsupporting

confidence: 72%

Section: The Renal Ecb Systemmentioning

confidence: 99%

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The emerging role of the endocannabinoid system in the pathogenesis and treatment of kidney diseases

Tam

2015

Journal of Basic and Clinical Physiology and Pharmacology

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“…Palmitic acid, a player in renal tubular damage, upregulates CB1 mRNA and protein expression and promotes receptor internalization, and, by activating endoplasmic reticulum stress, induces intrinsic pathway apoptosis via CB1 (480). Higher CB1 expression and internalization are also reported in primary rat mesangial cells exposed to high glucose (481), and CB1 is among the most upregulated genes in mice subjected to unilateral ureteral obstruction, an experimental model of renal fibrosis. In the fibrotic kidney, 2-AG levels are significantly increased, and genetic or pharmacological blockade of CB1 reduces fibrosis.…”

Section: Kidneymentioning

confidence: 99%

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

Ligresti¹,

Petrocellis²,

Marzo³

2016

Physiological Reviews

377

337

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Apart from having been used and misused for at least four millennia for, among others, recreational and medicinal purposes, the cannabis plant and its most peculiar chemical components, the plant cannabinoids (phytocannabinoids), have the merit to have led humanity to discover one of the most intriguing and pleiotropic endogenous signaling systems, the endocannabinoid system (ECS). This review article aims to describe and critically discuss, in the most comprehensive possible manner, the multifaceted aspects of 1) the pharmacology and potential impact on mammalian physiology of all major phytocannabinoids, and not only of the most famous one ⌬ 9 -tetrahydrocannabinol, and 2) the adaptive prohomeostatic physiological, or maladaptive pathological, roles of the ECS in mammalian cells, tissues, and organs. In doing so, we have respected the chronological order of the milestones of the millennial route from medicinal/recreational cannabis to the ECS and beyond, as it is now clear that some of the early steps in this long path, which were originally neglected, are becoming important again. The emerging picture is rather complex, but still supports the belief that more important discoveries on human physiology, and new therapies, might come in the future from new knowledge in this field.

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“…13) High glucose-induced apoptosis via ER stress in primary cultured rat mesangial cells. 14) Therefore, ER stress inhibitor seems to be a promising strategy for DN prevention.…”

mentioning

confidence: 99%

Ursodeoxycholic Acid Ameliorated Diabetic Nephropathy by Attenuating Hyperglycemia-Mediated Oxidative Stress

Wang

Chen

et al. 2016

Biological & Pharmaceutical Bulletin

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Oxidative stress has a great role in diabetes and diabetes induced organ damage. Endoplasmic reticulum (ER) stress is involved in the onset of diabetic nephropathy. We hypothesize that ER stress inhibition could protect against kidney injury through anti-oxidative effects. To test whether block ER stress could attenuate oxidative stress and improve diabetic nephropathy in vivo and in vitro, the effect of ursodeoxycholic acid (UDCA), an ER stress inhibitor, on spontaneous diabetic nephropathy db/db mice, ER stress inducer or high glucose-triggered podocytes were studied. Mice were assigned to 3 groups (n 6 per group): control group (treated with vehicle), db/db group (treated with vehicle), and UDCA group (db/db mice treated with 40 mg/ kg/d UDCA). After 8 weeks treatment, mice were sacrificed. Blood and kidneys were collected for the assessment of albumin/creatinine ratio, blood urea nitrogen (BUN), serum creatinine (SCr), insulin, total cholesterol, triglyceride, low density lipoprotein cholesterol (LDL-C), oxidized LDL-C, high density lipoprotein cholesterol (HDL-C), non-esterified fatty acid (NEFA), superoxide dismutase (SOD), catalase (CAT), methane dicarboxylic aldehyde (MDA), the expressions of SOD isoforms and glutathione peroxidase 1, as well as histopathological examination. In addition, generation of reactive oxygen species (ROS) was detected by 2′7′-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescence. The results showed that UDCA alleviated renal ER stress-evoked cell death, oxidative stress, renal dysfunction, ROS production, upregulated the expression of Bcl-2 and suppressed Bax in vivo and in vitro. Hence, inhibition ER stress diminishes oxidative stress and exerts renoprotective effects.Key words diabetic nephropathy; podocyte; oxidative stress; reactive oxygen species Diabetic mellitus is a global health problem in which blood glucose is persistently elevated and generates a cascade of events in organ including kidney.1,2) The population with diabetes has been increasing worldwide and diabetic nephropathy (DN) now is a leading cause of end-stage renal failure.3)The mechanisms by which hyperglycemia contributes to kidney remain limited due to various factors modulate the plasma glucose in the body. The management of DN is based on the control of plasma glucose levels. 4) Reviewing number of studies demonstrates that reactive oxygen species (ROS), associated with increased plasma glucose, has been implicated in the pathogenesis of DN, which results in the over-production of extracellular matrix proteins, mitochondrial damage and glomeruli injury.5-8) Therefore, oxidative stress attenuation is an important pathway in DN prevention. 9)The endoplasmic reticulum (ER) regulates the folding of secretory and intracellular calcium.10) Excessive unfolded proteins in the lumen of ER produces stress and contributed to the disorder of intracellular signal transduction pathways. 11)A number of pathophysiological conditions are associated with ER stress included diabetes. ER stress is a key mediator of β...

show abstract

Cannabinoid receptor 1 mediates high glucose-induced apoptosis via endoplasmic reticulum stress in primary cultured rat mesangial cells

Cited by 44 publications

References 64 publications

The emerging role of the endocannabinoid system in the pathogenesis and treatment of kidney diseases

The emerging role of the endocannabinoid system in the pathogenesis and treatment of kidney diseases

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

Ursodeoxycholic Acid Ameliorated Diabetic Nephropathy by Attenuating Hyperglycemia-Mediated Oxidative Stress

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