Isoproterenol decreases LDL receptor expression in rat adipose cells: activation of cyclic AMP-dependent proteolysis

Kraemer, Fredric B.; Natu, Vanita; Singh-Bist, Anita; Patel, Shushma; Komaromy, Michael; Medicherla, Satyanarayana; Azhar, Salman; Sztalryd, Carole

doi:10.1016/s0022-2275(20)37612-4

Cited by 6 publications

(3 citation statements)

References 38 publications

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“…Our finding of 160 kDa LDL-R and 95-, 75 and 65 kDa proteins in testis agrees with the report of these bands in adipocytes isolated from the rat epidydimal fat pad ( Kraemer et al, 1996 ). A 120 kDa LDL-R immunoreactive band corresponding to the non O-glycosylated form was described in whole testis extracts ( Eacker et al, 2008 ).…”

Section: Discussionsupporting

confidence: 93%

“…The localization of PCSK9 in the spermatozoon’s acrosome raises the issue of the convertase significance in the sperm-oocyte interaction and fertilisation process. Our immunolocalisation of LDL-R in the acrosome is in line with the report of LDL-R in intracellular membranes associated with enzyme markers of the Golgi apparatus and plasma membranes ( Kraemer et al, 1996 ). The (N- and O-glycosylated) 160 kDa form of LDL-R predominated in tubules whereas non O-glycosylated 120 kDa-LDL-R and fragments prevailed in spermatozoa.…”

Section: Discussionsupporting

confidence: 91%

“…A 120 kDa LDL-R immunoreactive band corresponding to the non O-glycosylated form was described in whole testis extracts ( Eacker et al, 2008 ). The smaller sized LDL-R immunoreactive bands are like proteolytic fragments based on the observation that only acetyl-leucine-leucine-methionine (ALLM), an inhibitor of cysteine proteases, prevented the isoproterenol-stimulated proteolysis of LDL-R ( Kraemer et al, 1996 ). The lack of PCSK9 would be expected to lower cholesterol in blood by augmenting the number of LDL-Rs in liver as this was reported in Pcsk9 -deficient mice ( Rashid et al, 2005 ; Zaid et al, 2008 ).…”

Section: Discussionmentioning

confidence: 99%

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PCSK9 Contributes to the Cholesterol, Glucose, and Insulin2 Homeostasis in Seminiferous Tubules and Maintenance of Immunotolerance in Testis

Pelletier

Layeghkhavidaki

Seidah

et al. 2022

Front. Cell Dev. Biol.

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The PCSK9 contribution to cholesterol and immunotolerance homeostasis and response to glucose, and insulin in testis and hypophysis were studied using Pcsk9-deficient (−/−) and transgenic [Tg (PCSK9)] mice, and diabetic, obese ob/ob and db/db mice. The spermatids/spermatozoa acrosome, peritubular vessels, and epididymal adipocytes were PCSK9- and LDL-R-positive. The pro-PCSK9/PCSK9 ratio was high in interstitial tissue-fractions (ITf) and spermatozoa and low in seminiferous tubule-fractions (STf) in normal adult mice. This ratio decreased in ITf in ob/ob and db/db mice but increased in tubules in ob/ob mice. Deleting pcsk9 lowered cholesterol in serum but increased testicular cholesterol. Furthermore, HMGCoA-red, ACAT-2 and LDL-R turnover increased whereas SR-BI decreased in ITf; in tubules, ABCA1 decreased and 160 kDa LDL-R increased in Pcsk9−/− mice. Excess testicular cholesterol could result from increased cholesterol synthesis and uptake with reduction in SR-BI-mediated efflux in ITf and from the overload of apoptotic cells, lowered ABCA1-mediated efflux and stimulated LDL-R protein synthesis in tubules in Pcsk9−/− mice. Concomitantly with the cholesterol accumulation, tubules showed infiltrates of immune cells, elevated IL-17A and IL-17RA, and changes in the immunotolerance homeostasis. PCSK9 deficiency decreased glucose in tubules and spermatozoa while increasing insulin2 in ITf and tubules not serum. Moreover, IR-α, and IR-β augmented in tubules but decreased in the anterior pituitary; IR-α increased whereas IR-β decreased in ITf. The histology and cholesterol levels were normal in Tg (PCSK9) mouse testis. The excess cholesterol creates a milieu favorable to the action of high IL-17A and IL-17RA, the development of inflammatory conditions and self-tolerance breakdown in testis.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 91%